Cow’s Milk and Immune Function in the Respiratory Tract: Potential Mechanisms

PubMed Central

Perdijk, Olaf; van Splunter, Marloes; Savelkoul, Huub F. J.; Brugman, Sylvia; van Neerven, R. J. Joost

2018-01-01

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow’s milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention. PMID:29483908

Cow's Milk and Immune Function in the Respiratory Tract: Potential Mechanisms.

PubMed

Perdijk, Olaf; van Splunter, Marloes; Savelkoul, Huub F J; Brugman, Sylvia; van Neerven, R J Joost

2018-01-01

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow's milk. Indeed, recent studies show inverse associations between raw cow's milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow's milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow's milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow's milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow's milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow's milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow's milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.

Altered Mitochondria, Protein Synthesis Machinery, and Purine Metabolism Are Molecular Contributors to the Pathogenesis of Creutzfeldt-Jakob Disease.

PubMed

Ansoleaga, Belén; Garcia-Esparcia, Paula; Llorens, Franc; Hernández-Ortega, Karina; Carmona Tech, Margarita; Antonio Del Rio, José; Zerr, Inga; Ferrer, Isidro

2016-06-12

Neuron loss, synaptic decline, and spongiform change are the hallmarks of sporadic Creutzfeldt-Jakob disease (sCJD), and may be related to deficiencies in mitochondria, energy metabolism, and protein synthesis. To investigate these relationships, we determined the expression levels of genes encoding subunits of the 5 protein complexes of the electron transport chain, proteins involved in energy metabolism, nucleolar and ribosomal proteins, and enzymes of purine metabolism in frontal cortex samples from 15 cases of sCJD MM1 and age-matched controls. We also assessed the protein expression levels of subunits of the respiratory chain, initiation and elongation translation factors of protein synthesis, and localization of selected mitochondrial components. We identified marked, generalized alterations of mRNA and protein expression of most subunits of all 5 mitochondrial respiratory chain complexes in sCJD cases. Expression of molecules involved in protein synthesis and purine metabolism were also altered in sCJD. These findings point to altered mRNA and protein expression of components of mitochondria, protein synthesis machinery, and purine metabolism as components of the pathogenesis of CJD. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

Respiratory hospitalizations in association with fine PM and its components in New York State.

PubMed

Jones, Rena R; Hogrefe, Christian; Fitzgerald, Edward F; Hwang, Syni-An; Özkaynak, Halûk; Garcia, Valerie C; Lin, Shao

2015-05-01

Despite observed geographic and temporal variation in particulate matter (PM)-related health morbidities, only a small number of epidemiologic studies have evaluated the relation between PM2.5 chemical constituents and respiratory disease. Most assessments are limited by inadequate spatial and temporal resolution of ambient PM measurements and/or by their approaches to examine the role of specific PM components on health outcomes. In a case-crossover analysis using daily average ambient PM2.5 total mass and species estimates derived from the Community Multiscale Air Quality (CMAQ) model and available observations, we examined the association between the chemical components of PM (including elemental and organic carbon, sulfate, nitrate, ammonium, and other remaining) and respiratory hospitalizations in New York State. We evaluated relationships between levels (low, medium, high) of PM constituent mass fractions, and assessed modification of the PM2.5-hospitalization association via models stratified by mass fractions of both primary and secondary PM components. In our results, average daily PM2.5 concentrations in New York State were generally lower than the 24-hr average National Ambient Air Quality Standard (NAAQS). Year-round analyses showed statistically significant positive associations between respiratory hospitalizations and PM2.5 total mass, sulfate, nitrate, and ammonium concentrations at multiple exposure lags (0.5-2.0% per interquartile range [IQR] increase). Primarily in the summer months, the greatest associations with respiratory hospitalizations were observed per IQR increase in the secondary species sulfate and ammonium concentrations at lags of 1-4 days (1.0-2.0%). Although there were subtle differences in associations observed between mass fraction tertiles, there was no strong evidence to support modification of the PM2.5-respiratory disease association by a particular constituent. We conclude that ambient concentrations of PM2.5 and secondary aerosols including sulfate, ammonium, and nitrate were positively associated with respiratory hospitalizations, although patterns varied by season. Exposure to specific fine PM constituents is a plausible risk factor for respiratory hospitalization in New York State. The association between ambient concentrations of PM2.5 components has been evaluated in only a small number of epidemiologic studies with refined spatial and temporal scale data. In New York State, fine PM and several of its constituents, including sulfate, ammonium, and nitrate, were positively associated with respiratory hospitalizations. Results suggest that PM species relationships and their influence on respiratory endpoints are complex and season dependent. Additional work is needed to better understand the relative toxicity of PM species, and to further explore the role of co-pollutant relationships and exposure prediction error on observed PM-respiratory disease associations.

Conceptual Model for Assessing Criteria Air Pollutants in a Multipollutant Context: A Modified Adverse Outcome Pathway Approach

EPA Science Inventory

Background: Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is d...

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function.

PubMed

Floyd, Brendan J; Wilkerson, Emily M; Veling, Mike T; Minogue, Catie E; Xia, Chuanwu; Beebe, Emily T; Wrobel, Russell L; Cho, Holly; Kremer, Laura S; Alston, Charlotte L; Gromek, Katarzyna A; Dolan, Brendan K; Ulbrich, Arne; Stefely, Jonathan A; Bohl, Sarah L; Werner, Kelly M; Jochem, Adam; Westphall, Michael S; Rensvold, Jarred W; Taylor, Robert W; Prokisch, Holger; Kim, Jung-Ja P; Coon, Joshua J; Pagliarini, David J

2016-08-18

Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function. Copyright © 2016 Elsevier Inc. All rights reserved.

Coenzyme Q biosynthesis and its role in the respiratory chain structure.

PubMed

Alcázar-Fabra, María; Navas, Plácido; Brea-Calvo, Gloria

2016-08-01

Coenzyme Q (CoQ) is a unique electron carrier in the mitochondrial respiratory chain, which is synthesized on-site by a nuclear encoded multiprotein complex. CoQ receives electrons from different redox pathways, mainly NADH and FADH2 from tricarboxylic acid pathway, dihydroorotate dehydrogenase, electron transfer flavoprotein dehydrogenase and glycerol-3-phosphate dehydrogenase that support key aspects of the metabolism. Here we explore some lines of evidence supporting the idea of the interaction of CoQ with the respiratory chain complexes, contributing to their superassembly, including respirasome, and its role in reactive oxygen species production in the mitochondrial inner membrane. We also review the current knowledge about the involvement of mitochondrial genome defects and electron transfer flavoprotein dehydrogenase mutations in the induction of secondary CoQ deficiency. This mechanism would imply specific interactions coupling CoQ itself or the CoQ-biosynthetic apparatus with the respiratory chain components. These interactions would regulate mitochondrial CoQ steady-state levels and function. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. Copyright © 2016 Elsevier B.V. All rights reserved.

Cross-shift study of exposure–response relationships between bioaerosol exposure and respiratory effects in the Norwegian grain and animal feed production industry

PubMed Central

Straumfors, Anne; Heldal, Kari Kulvik; Eduard, Wijnand; Wouters, Inge M; Ellingsen, Dag G; Skogstad, Marit

2016-01-01

Objective We have studied cross-shift respiratory responses of several individual bioaerosol components of the dust in the grain and feed industry in Norway. Methods Cross-shift changes in lung function and nasal congestion, as well as in respiratory and systemic symptoms of 56 exposed workers and 36 referents, were recorded on the same day as full-shift exposure to the inhalable aerosol fraction was assessed. Exposure–response associations were investigated by regression analysis. Results The workers were exposed on average to 1.0 mg/m3 of grain dust, 440 EU/m3 of endotoxin, 6 µg/m3 of β-1,3-glucans, 17×104/m3 of bacteria and 4×104/m3 of fungal spores during work. The exposure was associated with higher prevalence of self-reported eye and airway symptoms, which were related to the individual microbial components in a complex manner. Fatigue and nose symptoms were strongest associated with fungal spores, cough with or without phlegm was associated with grain dust and fungal spores equally strong and wheeze/tight chest/dyspnoea was strongest associated with grain dust. Bioaerosol exposure did not lead to cross-shift lung function decline, but several microbial components had influence on nose congestion. Conclusions Exposure to fungal spores and dust showed stronger associations with respiratory symptoms and fatigue than endotoxin exposure. The associations with dust suggest that there are other components in dust than the ones studied that induce these effects. PMID:27473330

Fluctuations and Noise in Stochastic Spread of Respiratory Infection Epidemics in Social Networks

NASA Astrophysics Data System (ADS)

Yulmetyev, Renat; Emelyanova, Natalya; Demin, Sergey; Gafarov, Fail; Hänggi, Peter; Yulmetyeva, Dinara

2003-05-01

For the analysis of epidemic and disease dynamics complexity, it is necessary to understand the basic principles and notions of its spreading in long-time memory media. Here we considering the problem from a theoretical and practical viewpoint, presenting the quantitative evidence confirming the existence of stochastic long-range memory and robust chaos in a real time series of respiratory infections of human upper respiratory track. In this work we present a new statistical method of analyzing the spread of grippe and acute respiratory track infections epidemic process of human upper respiratory track by means of the theory of discrete non-Markov stochastic processes. We use the results of our recent theory (Phys. Rev. E 65, 046107 (2002)) for the study of statistical effects of memory in real data series, describing the epidemic dynamics of human acute respiratory track infections and grippe. The obtained results testify to an opportunity of the strict quantitative description of the regular and stochastic components in epidemic dynamics of social networks with a view to time discreteness and effects of statistical memory.

A Molecular atlas of Xenopus respiratory system development.

PubMed

Rankin, Scott A; Thi Tran, Hong; Wlizla, Marcin; Mancini, Pamela; Shifley, Emily T; Bloor, Sean D; Han, Lu; Vleminckx, Kris; Wert, Susan E; Zorn, Aaron M

2015-01-01

Respiratory system development is regulated by a complex series of endoderm-mesoderm interactions that are not fully understood. Recently Xenopus has emerged as an alternative model to investigate early respiratory system development, but the extent to which the morphogenesis and molecular pathways involved are conserved between Xenopus and mammals has not been systematically documented. In this study, we provide a histological and molecular atlas of Xenopus respiratory system development, focusing on Nkx2.1+ respiratory cell fate specification in the developing foregut. We document the expression patterns of Wnt/β-catenin, fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) signaling components in the foregut and show that the molecular mechanisms of respiratory lineage induction are remarkably conserved between Xenopus and mice. Finally, using several functional experiments we refine the epistatic relationships among FGF, Wnt, and BMP signaling in early Xenopus respiratory system development. We demonstrate that Xenopus trachea and lung development, before metamorphosis, is comparable at the cellular and molecular levels to embryonic stages of mouse respiratory system development between embryonic days 8.5 and 10.5. This molecular atlas provides a fundamental starting point for further studies using Xenopus as a model to define the conserved genetic programs controlling early respiratory system development. © 2014 Wiley Periodicals, Inc.

Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.

PubMed

Singh, Namrata; Hroudová, Jana; Fišar, Zdeněk

2015-08-01

The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.

Respiratory chain deficiency in aged spinal motor neurons☆

PubMed Central

Rygiel, Karolina A.; Grady, John P.; Turnbull, Doug M.

2014-01-01

Sarcopenia, muscle wasting, and strength decline with age, is an important cause of loss of mobility in the elderly individuals. The underlying mechanisms are uncertain but likely to involve defects of motor nerve, neuromuscular junction, and muscle. Loss of motor neurons with age and subsequent denervation of skeletal muscle has been recognized as one of the contributing factors. This study investigated aspects of mitochondrial biology in spinal motor neurons from elderly subjects. We found that protein components of complex I of mitochondrial respiratory chain were reduced or absent in a proportion of aged motor neurons–a phenomenon not observed in fetal tissue. Further investigation showed that complex I-deficient cells had reduced mitochondrial DNA content and smaller soma size. We propose that mitochondrial dysfunction in these motor neurons could lead to the cell loss and ultimately denervation of muscle fibers. PMID:24684792

Cross-shift study of exposure-response relationships between bioaerosol exposure and respiratory effects in the Norwegian grain and animal feed production industry.

PubMed

Straumfors, Anne; Heldal, Kari Kulvik; Eduard, Wijnand; Wouters, Inge M; Ellingsen, Dag G; Skogstad, Marit

2016-10-01

We have studied cross-shift respiratory responses of several individual bioaerosol components of the dust in the grain and feed industry in Norway. Cross-shift changes in lung function and nasal congestion, as well as in respiratory and systemic symptoms of 56 exposed workers and 36 referents, were recorded on the same day as full-shift exposure to the inhalable aerosol fraction was assessed. Exposure-response associations were investigated by regression analysis. The workers were exposed on average to 1.0 mg/m(3) of grain dust, 440 EU/m(3) of endotoxin, 6 µg/m(3) of β-1,3-glucans, 17×10(4)/m(3) of bacteria and 4×10(4)/m(3) of fungal spores during work. The exposure was associated with higher prevalence of self-reported eye and airway symptoms, which were related to the individual microbial components in a complex manner. Fatigue and nose symptoms were strongest associated with fungal spores, cough with or without phlegm was associated with grain dust and fungal spores equally strong and wheeze/tight chest/dyspnoea was strongest associated with grain dust. Bioaerosol exposure did not lead to cross-shift lung function decline, but several microbial components had influence on nose congestion. Exposure to fungal spores and dust showed stronger associations with respiratory symptoms and fatigue than endotoxin exposure. The associations with dust suggest that there are other components in dust than the ones studied that induce these effects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Programming of respiratory health in childhood: influence of outdoor air pollution.

PubMed

Wright, Rosalind J; Brunst, Kelly J

2013-04-01

This overview highlights recent experimental and epidemiological evidence for the programming effects of outdoor air pollution exposures during early development on lung function and chronic respiratory disorders, such as asthma and related allergic disorders. Air pollutants may impact anatomy and/or physiological functioning of the lung and interrelated systems. Programming effects may result from pollutant-induced shifts in a number of molecular, cellular, and physiological states and their interacting systems. Specific key regulatory systems susceptible to programming may influence lung development and vulnerability to respiratory diseases, including both central and peripheral components of neuroendocrine pathways and autonomic nervous system (ANS) functioning which, in turn, influence the immune system. Starting in utero, environmental factors, including air pollutants, may permanently organize these systems toward trajectories of enhanced pediatric (e.g., asthma, allergy) as well as adult disease risk (e.g., chronic obstructive pulmonary disease). Evidence supports a central role of oxidative stress in the toxic effects of air pollution. Additional research suggests xenobiotic metabolism and subcellular components, such as mitochondria are targets of ambient air pollution and play a role in asthma and allergy programming. Mechanisms operating at the level of the placenta are being elucidated. Epigenetic mechanisms may be at the roots of adaptive developmental programming. Optimal coordinated functioning of many complex processes and their networks of interaction are necessary for normal lung development and the maintenance of respiratory health. Outdoor air pollution may play an important role in early programming of respiratory health and is potentially amenable to intervention.

AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress

PubMed Central

Sriskanthadevan, Shrivani; Jeyaraju, Danny V.; Chung, Timothy E.; Prabha, Swayam; Xu, Wei; Skrtic, Marko; Jhas, Bozhena; Hurren, Rose; Gronda, Marcela; Wang, Xiaoming; Jitkova, Yulia; Sukhai, Mahadeo A.; Lin, Feng-Hsu; Maclean, Neil; Laister, Rob; Goard, Carolyn A.; Mullen, Peter J.; Xie, Stephanie; Penn, Linda Z.; Rogers, Ian M.; Dick, John E.; Minden, Mark D.

2015-01-01

Mitochondrial respiration is a crucial component of cellular metabolism that can become dysregulated in cancer. Compared with normal hematopoietic cells, acute myeloid leukemia (AML) cells and patient samples have higher mitochondrial mass, without a concomitant increase in respiratory chain complex activity. Hence these cells have a lower spare reserve capacity in the respiratory chain and are more susceptible to oxidative stress. We therefore tested the effects of increasing the electron flux through the respiratory chain as a strategy to induce oxidative stress and cell death preferentially in AML cells. Treatment with the fatty acid palmitate induced oxidative stress and cell death in AML cells, and it suppressed tumor burden in leukemic cell lines and primary patient sample xenografts in the absence of overt toxicity to normal cells and organs. These data highlight a unique metabolic vulnerability in AML, and identify a new therapeutic strategy that targets abnormal oxidative metabolism in this malignancy. PMID:25631767

Synchrosqueezing an effective method for analyzing Doppler radar physiological signals.

PubMed

Yavari, Ehsan; Rahman, Ashikur; Jia Xu; Mandic, Danilo P; Boric-Lubecke, Olga

2016-08-01

Doppler radar can monitor vital sign wirelessly. Respiratory and heart rate have time-varying behavior. Capturing the rate variability provides crucial physiological information. However, the common time-frequency methods fail to detect key information. We investigate Synchrosqueezing method to extract oscillatory components of the signal with time varying spectrum. Simulation and experimental result shows the potential of the proposed method for analyzing signals with complex time-frequency behavior like physiological signals. Respiration and heart signals and their components are extracted with higher resolution and without any pre-filtering and signal conditioning.

Biogenesis of the yeast cytochrome bc1 complex.

PubMed

Zara, Vincenzo; Conte, Laura; Trumpower, Bernard L

2009-01-01

The mitochondrial respiratory chain is composed of four different protein complexes that cooperate in electron transfer and proton pumping across the inner mitochondrial membrane. The cytochrome bc1 complex, or complex III, is a component of the mitochondrial respiratory chain. This review will focus on the biogenesis of the bc1 complex in the mitochondria of the yeast Saccharomyces cerevisiae. In wild type yeast mitochondrial membranes the major part of the cytochrome bc1 complex was found in association with one or two copies of the cytochrome c oxidase complex. The analysis of several yeast mutant strains in which single genes or pairs of genes encoding bc1 subunits had been deleted revealed the presence of a common set of bc1 sub-complexes. These sub-complexes are represented by the central core of the bc1 complex, consisting of cytochrome b bound to subunit 7 and subunit 8, by the two core proteins associated with each other, by the Rieske protein associated with subunit 9, and by those deriving from the unexpected interaction of each of the two core proteins with cytochrome c1. Furthermore, a higher molecular mass sub-complex is that composed of cytochrome b, cytochrome c1, core protein 1 and 2, subunit 6, subunit 7 and subunit 8. The identification and characterization of all these sub-complexes may help in defining the steps and the molecular events leading to bc1 assembly in yeast mitochondria.

Recent advances on the functional and evolutionary morphology of the amniote respiratory apparatus.

PubMed

Lambertz, Markus

2016-02-01

Increased organismic complexity in metazoans was achieved via the specialization of certain parts of the body involved in different faculties (structure-function complexes). One of the most basic metabolic demands of animals in general is a sufficient supply of all tissues with oxygen. Specialized structures for gas exchange (and transport) consequently evolved many times and in great variety among bilaterians. This review focuses on some of the latest advancements that morphological research has added to our understanding of how the respiratory apparatus of the primarily terrestrial vertebrates (amniotes) works and how it evolved. Two main components of the respiratory apparatus, the lungs as the "exchanger" and the ventilatory apparatus as the "active pump," are the focus of this paper. Specific questions related to the exchanger concern the structure of the lungs of the first amniotes and the efficiency of structurally simple snake lungs in health and disease, as well as secondary functions of the lungs in heat exchange during the evolution of sauropod dinosaurs. With regard to the active pump, I discuss how the unique ventilatory mechanism of turtles evolved and how understanding the avian ventilatory strategy affects animal welfare issues in the poultry industry. © 2016 New York Academy of Sciences.

Dysfunctional Coq9 protein causes predominant encephalomyopathy associated with CoQ deficiency.

PubMed

García-Corzo, Laura; Luna-Sánchez, Marta; Doerrier, Carolina; García, José A; Guarás, Adela; Acín-Pérez, Rebeca; Bullejos-Peregrín, Javier; López, Ana; Escames, Germaine; Enríquez, José A; Acuña-Castroviejo, Darío; López, Luis C

2013-03-15

Coenzyme Q10 (CoQ(10)) or ubiquinone is a well-known component of the mitochondrial respiratory chain. In humans, CoQ(10) deficiency causes a mitochondrial syndrome with an unexplained variability in the clinical presentations. To try to understand this heterogeneity in the clinical phenotypes, we have generated a Coq9 Knockin (R239X) mouse model. The lack of a functional Coq9 protein in homozygous Coq9 mutant (Coq9(X/X)) mice causes a severe reduction in the Coq7 protein and, as consequence, a widespread CoQ deficiency and accumulation of demethoxyubiquinone. The deficit in CoQ induces a brain-specific impairment of mitochondrial bioenergetics performance, a reduction in respiratory control ratio, ATP levels and ATP/ADP ratio and specific loss of respiratory complex I. These effects lead to neuronal death and demyelinization with severe vacuolization and astrogliosis in the brain of Coq9(X/X) mice that consequently die between 3 and 6 months of age. These results suggest that the instability of mitochondrial complex I in the brain, as a primary event, triggers the development of mitochondrial encephalomyopathy associated with CoQ deficiency.

Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment

PubMed Central

Chowdhury, Subir K. Roy; Zherebitskaya, Elena; Smith, Darrell R.; Akude, Eli; Chattopadhyay, Sharmila; Jolivalt, Corinne G.; Calcutt, Nigel A.; Fernyhough, Paul

2010-01-01

OBJECTIVE Impairments in mitochondrial physiology may play a role in diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in sensory neurons is due to abnormal mitochondrial respiratory function. RESEARCH DESIGN AND METHODS Rates of oxygen consumption were measured in mitochondria from dorsal root ganglia (DRG) of 12- to- 22-week streptozotocin (STZ)-induced diabetic rats, diabetic rats treated with insulin, and age-matched controls. Activities and expression of components of mitochondrial complexes and reactive oxygen species (ROS) were analyzed. RESULTS Rates of coupled respiration with pyruvate + malate (P + M) and with ascorbate + TMPD (Asc + TMPD) in DRG were unchanged after 12 weeks of diabetes. By 22 weeks of diabetes, respiration with P + M was significantly decreased by 31–44% and with Asc + TMPD by 29–39% compared with control. Attenuated mitochondrial respiratory activity of STZ-diabetic rats was significantly improved by insulin that did not correct other indices of diabetes. Activities of mitochondrial complexes I and IV and the Krebs cycle enzyme, citrate synthase, were decreased in mitochondria from DRG of 22-week STZ-diabetic rats compared with control. ROS levels in perikarya of DRG neurons were not altered by diabetes, but ROS generation from mitochondria treated with antimycin A was diminished compared with control. Reduced mitochondrial respiratory function was associated with downregulation of expression of mitochondrial proteins. CONCLUSIONS Mitochondrial dysfunction in sensory neurons from type 1 diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS. PMID:20103706

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

PubMed Central

Koit, Andre; Ounpuu, Lyudmila; Klepinin, Aleksandr; Chekulayev, Vladimir; Timohhina, Natalja; Tepp, Kersti; Puurand, Marju; Truu, Laura; Heck, Karoliina; Valvere, Vahur; Guzun, Rita

2017-01-01

We conducted quantitative cellular respiration analysis on samples taken from human breast cancer (HBC) and human colorectal cancer (HCC) patients. Respiratory capacity is not lost as a result of tumor formation and even though, functionally, complex I in HCC was found to be suppressed, it was not evident on the protein level. Additionally, metabolic control analysis was used to quantify the role of components of mitochondrial interactosome. The main rate-controlling steps in HBC are complex IV and adenine nucleotide transporter, but in HCC, complexes I and III. Our kinetic measurements confirmed previous studies that respiratory chain complexes I and III in HBC and HCC can be assembled into supercomplexes with a possible partial addition from the complex IV pool. Therefore, the kinetic method can be a useful addition in studying supercomplexes in cell lines or human samples. In addition, when results from culture cells were compared to those from clinical samples, clear differences were present, but we also detected two different types of mitochondria within clinical HBC samples, possibly linked to two-compartment metabolism. Taken together, our data show that mitochondrial respiration and regulation of mitochondrial membrane permeability have substantial differences between these two cancer types when compared to each other to their adjacent healthy tissue or to respective cell cultures. PMID:28781720

Cold and Heat Stress Diversely Alter Both Cauliflower Respiration and Distinct Mitochondrial Proteins Including OXPHOS Components and Matrix Enzymes

PubMed Central

Rurek, Michał; Czołpińska, Magdalena; Pawłowski, Tomasz Andrzej; Krzesiński, Włodzimierz; Spiżewski, Tomasz

2018-01-01

Complex proteomic and physiological approaches for studying cold and heat stress responses in plant mitochondria are still limited. Variations in the mitochondrial proteome of cauliflower (Brassica oleracea var. botrytis) curds after cold and heat and after stress recovery were assayed by two-dimensional polyacrylamide gel electrophoresis (2D PAGE) in relation to mRNA abundance and respiratory parameters. Quantitative analysis of the mitochondrial proteome revealed numerous stress-affected protein spots. In cold, major downregulations in the level of photorespiratory enzymes, porine isoforms, oxidative phosphorylation (OXPHOS) and some low-abundant proteins were observed. In contrast, carbohydrate metabolism enzymes, heat-shock proteins, translation, protein import, and OXPHOS components were involved in heat response and recovery. Several transcriptomic and metabolic regulation mechanisms are also suggested. Cauliflower plants appeared less susceptible to heat; closed stomata in heat stress resulted in moderate photosynthetic, but only minor respiratory impairments, however, photosystem II performance was unaffected. Decreased photorespiration corresponded with proteomic alterations in cold. Our results show that cold and heat stress not only operate in diverse modes (exemplified by cold-specific accumulation of some heat shock proteins), but exert some associations at molecular and physiological levels. This implies a more complex model of action of investigated stresses on plant mitochondria. PMID:29547512

Learning and transfer in motor-respiratory coordination.

PubMed

Hessler, Eric E; Amazeen, Polemnia G

2014-02-01

Motor-respiratory coordination occurs naturally during exercise, but the number of coordination patterns performed between movement and breathing is limited. We investigated whether participants could acquire novel ratios (either 5:2 or 5:3). To examine complex temporal relationships between movement and breathing, we used lagged return plots that were produced by graphing relative phase against relative phase after a time delay. By the end of practice, participants performed 5:2 consistently and performed 5:3 using more stable ratios (3:2 and 2:1). Lagged return plots revealed that 5:3 learners harnessed the stable inphase and antiphase patterns to stabilize the required ratio. That strategy resulted in the performance of smaller-integer ratios in the production of 5:3 but not 5:2. Despite those differences, there was positive transfer to unpracticed ratios that was similar in both learning conditions. The time series analysis of lagged return plots revealed differences in ratio performance at transfer. Ratios whose component frequencies were farther apart, like 7:2, were performed consistently, while ratios whose component frequencies were more similar, like 5:4, elicited attraction to inphase and antiphase. The implication is that participants can combine more stable chunks of rhythmic behavior to produce more complex ratios. Copyright © 2013 Elsevier B.V. All rights reserved.

The phagocyte respiratory burst: Historical perspectives and recent advances.

PubMed

Thomas, David C

2017-12-01

When exposed to certain stimuli, phagocytes (including neutrophils, macrophages and eosinophils) undergo marked changes in the way they handle oxygen. Firstly, their rate of oxygen uptake increases greatly. This is accompanied by (i) the production of large amounts of superoxide and hydrogen peroxide and (ii) the metabolism of large quantities of glucose through the hexose monophosphate shunt. We now know that the oxygen used is not for respiration but for the production of powerful microbiocidal agents downstream of the initial production of superoxide. Concomitantly, glucose is oxidised through the hexose monophosphate shunt to re-generate the NADPH that has been consumed through the reduction of molecular oxygen to generate superoxide. This phagocyte respiratory burst is generated by an NADPH oxidase multi-protein complex that has a catalytic core consisting of membrane-bound gp91phox (CYBB) and p22phox (CYBA) sub-units and cytosolic components p47phox (NCF1), p67phox (NCF2) and p40phox (NCF4). Finally, another cytosolic component, the small G-protein Rac (Rac2 in neutrophils and Rac1 in macrophages) is also required for full activation. The importance of the complex in host defence is underlined by chronic granulomatous disease, a severe life-limiting immunodeficiency caused by mutations in the genes encoding the individual subunits. In this review, I will discuss the experimental evidence that underlies our knowledge of the respiratory burst, outlining how elegant biochemical analysis, coupled with study of patients deficient in the various subunits has helped elucidate the function of this essential part of innate immunity. I will also discuss some exciting recent studies that shed new light on how the abundance of the various components is controlled. Finally, I will explore the emerging role of reactive oxygen species such as superoxide and hydrogen peroxide in the pathogenesis of major human diseases including auto-inflammatory diseases. Copyright © 2017. Published by Elsevier B.V.

Road dust and its effect on human health: a literature review

PubMed Central

2018-01-01

The purpose of this study was to determine the effects of road dust on human health. A PubMed search was used to extract references that included the words “road dust” and “health” or “fugitive dust” and “health” in the title or abstract. A total of 46 references were extracted and selected for review after the primary screening of 949 articles. The respiratory system was found to be the most affected system in the human body. Lead, platinum-group elements (platinum, rhodium, and bohrium), aluminum, zinc, vanadium, and polycyclic aromatic hydrocarbons were the components of road dust that were most frequently referenced in the articles reviewed. Road dust was found to have harmful effects on the human body, especially on the respiratory system. To determine the complex mechanism of action of various components of road dust on the human body and the results thereof, the authors recommend a further meta-analysis and extensive risk-assessment research into the health impacts of dust exposure. PMID:29642653

High Molecular Weight Forms of Mammalian Respiratory Chain Complex II

PubMed Central

Nůsková, Hana; Holzerová, Eliška; Vrbacký, Marek; Pecina, Petr; Hejzlarová, Kateřina; Kľučková, Katarína; Rohlena, Jakub; Neuzil, Jiri; Houštěk, Josef

2013-01-01

Mitochondrial respiratory chain is organised into supramolecular structures that can be preserved in mild detergent solubilisates and resolved by native electrophoretic systems. Supercomplexes of respiratory complexes I, III and IV as well as multimeric forms of ATP synthase are well established. However, the involvement of complex II, linking respiratory chain with tricarboxylic acid cycle, in mitochondrial supercomplexes is questionable. Here we show that digitonin-solubilised complex II quantitatively forms high molecular weight structures (CIIhmw) that can be resolved by clear native electrophoresis. CIIhmw structures are enzymatically active and differ in electrophoretic mobility between tissues (500 – over 1000 kDa) and cultured cells (400–670 kDa). While their formation is unaffected by isolated defects in other respiratory chain complexes, they are destabilised in mtDNA-depleted, rho0 cells. Molecular interactions responsible for the assembly of CIIhmw are rather weak with the complexes being more stable in tissues than in cultured cells. While electrophoretic studies and immunoprecipitation experiments of CIIhmw do not indicate specific interactions with the respiratory chain complexes I, III or IV or enzymes of the tricarboxylic acid cycle, they point out to a specific interaction between CII and ATP synthase. PMID:23967256

Diminished superoxide generation is associated with respiratory chain dysfunction and changes in the mitochondrial proteome of sensory neurons from diabetic rats.

PubMed

Akude, Eli; Zherebitskaya, Elena; Chowdhury, Subir K Roy; Smith, Darrell R; Dobrowsky, Rick T; Fernyhough, Paul

2011-01-01

Impairments in mitochondrial function have been proposed to play a role in the etiology of diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in axons of sensory neurons in type 1 diabetes is due to abnormal activity of the respiratory chain and an altered mitochondrial proteome. Proteomic analysis using stable isotope labeling with amino acids in cell culture (SILAC) determined expression of proteins in mitochondria from dorsal root ganglia (DRG) of control, 22-week-old streptozotocin (STZ)-diabetic rats, and diabetic rats treated with insulin. Rates of oxygen consumption and complex activities in mitochondria from DRG were measured. Fluorescence imaging of axons of cultured sensory neurons determined the effect of diabetes on mitochondrial polarization status, oxidative stress, and mitochondrial matrix-specific reactive oxygen species (ROS). Proteins associated with mitochondrial dysfunction, oxidative phosphorylation, ubiquinone biosynthesis, and the citric acid cycle were downregulated in diabetic samples. For example, cytochrome c oxidase subunit IV (COX IV; a complex IV protein) and NADH dehydrogenase Fe-S protein 3 (NDUFS3; a complex I protein) were reduced by 29 and 36% (P < 0.05), respectively, in diabetes and confirmed previous Western blot studies. Respiration and mitochondrial complex activity was significantly decreased by 15 to 32% compared with control. The axons of diabetic neurons exhibited oxidative stress and depolarized mitochondria, an aberrant adaption to oligomycin-induced mitochondrial membrane hyperpolarization, but reduced levels of intramitochondrial superoxide compared with control. Abnormal mitochondrial function correlated with a downregulation of mitochondrial proteins, with components of the respiratory chain targeted in lumbar DRG in diabetes. The reduced activity of the respiratory chain was associated with diminished superoxide generation within the mitochondrial matrix and did not contribute to oxidative stress in axons of diabetic neurons. Alternative pathways involving polyol pathway activity appear to contribute to raised ROS in axons of diabetic neurons under high glucose concentration.

Structural and Functional Analyses of the Proteins Involved in the Iron-Sulfur Cluster Biosynthesis

NASA Astrophysics Data System (ADS)

Wada, Kei

The iron-sulfur (Fe-S) clusters are ubiquitous prosthetic groups that are required to maintain such fundamental life processes as respiratory chain, photosynthesis and the regulation of gene expression. Assembly of intracellular Fe-S cluster requires the sophisticated biosynthetic systems called ISC and SUF machineries. To shed light on the molecular mechanism of Fe-S cluster assembly mediated by SUF machinery, several structures of the SUF components and their sub-complex were determined. The structural findings together with biochemical characterization of the core-complex (SufB-SufC-SufD complex) have led me to propose a working model for the cluster biosynthesis in the SUF machinery.

SLP-2 interacts with prohibitins in the mitochondrial inner membrane and contributes to their stability.

PubMed

Da Cruz, Sandrine; Parone, Philippe A; Gonzalo, Philippe; Bienvenut, Willy V; Tondera, Daniel; Jourdain, Alexis; Quadroni, Manfredo; Martinou, Jean-Claude

2008-05-01

Stomatin is a member of a large family of proteins including prohibitins, HflK/C, flotillins, mechanoreceptors and plant defense proteins, that are thought to play a role in protein turnover. Using different proteomic approaches, we and others have identified SLP-2, a member of the stomatin gene family, as a component of the mitochondria. In this study, we show that SLP-2 is strongly associated with the mitochondrial inner membrane and that it interacts with prohibitins. Depleting HeLa cells of SLP-2 lead to increased proteolysis of prohibitins and of subunits of the respiratory chain complexes I and IV. Further supporting the role of SLP-2 in regulating the stability of specific mitochondrial proteins, we found that SLP-2 is up-regulated under conditions of mitochondrial stress leading to increased protein turnover. These data indicate that SLP-2 plays a role in regulating the stability of mitochondrial proteins including prohibitins and subunits of respiratory chain complexes.

Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival.

PubMed

Pfleger, J; He, M; Abdellatif, M

2015-07-30

The survival of a cell depends on its ability to meet its energy requirements. We hypothesized that the mitochondrial reserve respiratory capacity (RRC) of a cell is a critical component of its bioenergetics that can be utilized during an increase in energy demand, thereby, enhancing viability. Our goal was to identify the elements that regulate and contribute to the development of RRC and its involvement in cell survival. The results show that activation of metabolic sensors, including pyruvate dehydrogenase and AMP-dependent kinase, increases cardiac myocyte RRC via a Sirt3-dependent mechanism. Notably, we identified mitochondrial complex II (cII) as a target of these metabolic sensors and the main source of RRC. Moreover, we show that RRC, via cII, correlates with enhanced cell survival after hypoxia. Thus, for the first time, we show that metabolic sensors via Sirt3 maximize the cellular RRC through activating cII, which enhances cell survival after hypoxia.

Extracellular DNA Is Essential for Maintaining Bordetella Biofilm Integrity on Abiotic Surfaces and in the Upper Respiratory Tract of Mice

PubMed Central

Deora, Rajendar

2011-01-01

Bacteria form complex and highly elaborate surface adherent communities known as biofilms which are held together by a self-produced extracellular matrix. We have previously shown that by adopting a biofilm mode of existence in vivo, the Gram negative bacterial pathogens Bordetella bronchiseptica and Bordetella pertussis are able to efficiently colonize and persist in the mammalian respiratory tract. In general, the bacterial biofilm matrix includes polysaccharides, proteins and extracellular DNA (eDNA). In this report, we investigated the function of DNA in Bordetella biofilm development. We show that DNA is a significant component of Bordetella biofilm matrix. Addition of DNase I at the initiation of biofilm growth inhibited biofilm formation. Treatment of pre-established mature biofilms formed under both static and flow conditions with DNase I led to a disruption of the biofilm biomass. We next investigated whether eDNA played a role in biofilms formed in the mouse respiratory tract. DNase I treatment of nasal biofilms caused considerable dissolution of the biofilm biomass. In conclusion, these results suggest that eDNA is a crucial structural matrix component of both in vitro and in vivo formed Bordetella biofilms. This is the first evidence for the ability of DNase I to disrupt bacterial biofilms formed on host organs. PMID:21347299

Effect of Rho-kinase inhibition on complexity of breathing pattern in a guinea pig model of asthma

PubMed Central

Pazhoohan, Saeed; Javan, Mohammad; Hajizadeh, Sohrab

2017-01-01

Asthma represents an episodic and fluctuating behavior characterized with decreased complexity of respiratory dynamics. Several evidence indicate that asthma severity or control is associated with alteration in variability of lung function. The pathophysiological basis of alteration in complexity of breathing pattern in asthma has remained poorly understood. Regarding the point that Rho-kinase is involved in pathophysiology of asthma, in present study we investigated the effect of Rho-kinase inhibition on complexity of respiratory dynamics in a guinea pig model of asthma. Male Dunkin Hartley guinea pigs were exposed to 12 series of inhalations with ovalbumin or saline. Animals were treated by the Rho-kinase inhibitor Y-27632 (1mM aerosols) prior to each allergen challenge. We recorded respiration of conscious animals using whole-body plethysmography. Exposure to ovalbumin induced lung inflammation, airway hyperresponsiveness and remodeling including goblet cell hyperplasia, increase in the thickness of airways smooth muscles and subepithelial collagen deposition. Complexity analysis of respiratory dynamics revealed a dramatic decrease in irregularity of respiratory rhythm representing less complexity in asthmatic guinea pigs. Inhibition of Rho-kinase reduced the airway remodeling and hyperreponsiveness, but had no significant effect on lung inflammation and complexity of respiratory dynamics in asthmatic animals. It seems that airway hyperresponsiveness and remodeling do not significantly affect the complexity of respiratory dynamics. Our results suggest that inflammation might be the probable cause of shift in the respiratory dynamics away from the normal fluctuation in asthma. PMID:29088265

Genomic, proteomic, and biochemical analysis of the organohalide respiratory pathway in Desulfitobacterium dehalogenans.

PubMed

Kruse, Thomas; van de Pas, Bram A; Atteia, Ariane; Krab, Klaas; Hagen, Wilfred R; Goodwin, Lynne; Chain, Patrick; Boeren, Sjef; Maphosa, Farai; Schraa, Gosse; de Vos, Willem M; van der Oost, John; Smidt, Hauke; Stams, Alfons J M

2015-03-01

Desulfitobacterium dehalogenans is able to grow by organohalide respiration using 3-chloro-4-hydroxyphenyl acetate (Cl-OHPA) as an electron acceptor. We used a combination of genome sequencing, biochemical analysis of redox active components, and shotgun proteomics to study elements of the organohalide respiratory electron transport chain. The genome of Desulfitobacterium dehalogenans JW/IU-DC1(T) consists of a single circular chromosome of 4,321,753 bp with a GC content of 44.97%. The genome contains 4,252 genes, including six rRNA operons and six predicted reductive dehalogenases. One of the reductive dehalogenases, CprA, is encoded by a well-characterized cprTKZEBACD gene cluster. Redox active components were identified in concentrated suspensions of cells grown on formate and Cl-OHPA or formate and fumarate, using electron paramagnetic resonance (EPR), visible spectroscopy, and high-performance liquid chromatography (HPLC) analysis of membrane extracts. In cell suspensions, these components were reduced upon addition of formate and oxidized after addition of Cl-OHPA, indicating involvement in organohalide respiration. Genome analysis revealed genes that likely encode the identified components of the electron transport chain from formate to fumarate or Cl-OHPA. Data presented here suggest that the first part of the electron transport chain from formate to fumarate or Cl-OHPA is shared. Electrons are channeled from an outward-facing formate dehydrogenase via menaquinones to a fumarate reductase located at the cytoplasmic face of the membrane. When Cl-OHPA is the terminal electron acceptor, electrons are transferred from menaquinones to outward-facing CprA, via an as-yet-unidentified membrane complex, and potentially an extracellular flavoprotein acting as an electron shuttle between the quinol dehydrogenase membrane complex and CprA. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Genomic, Proteomic, and Biochemical Analysis of the Organohalide Respiratory Pathway in Desulfitobacterium dehalogenans

PubMed Central

van de Pas, Bram A.; Atteia, Ariane; Krab, Klaas; Hagen, Wilfred R.; Goodwin, Lynne; Chain, Patrick; Boeren, Sjef; Maphosa, Farai; Schraa, Gosse; de Vos, Willem M.; van der Oost, John; Smidt, Hauke

2014-01-01

Desulfitobacterium dehalogenans is able to grow by organohalide respiration using 3-chloro-4-hydroxyphenyl acetate (Cl-OHPA) as an electron acceptor. We used a combination of genome sequencing, biochemical analysis of redox active components, and shotgun proteomics to study elements of the organohalide respiratory electron transport chain. The genome of Desulfitobacterium dehalogenans JW/IU-DC1T consists of a single circular chromosome of 4,321,753 bp with a GC content of 44.97%. The genome contains 4,252 genes, including six rRNA operons and six predicted reductive dehalogenases. One of the reductive dehalogenases, CprA, is encoded by a well-characterized cprTKZEBACD gene cluster. Redox active components were identified in concentrated suspensions of cells grown on formate and Cl-OHPA or formate and fumarate, using electron paramagnetic resonance (EPR), visible spectroscopy, and high-performance liquid chromatography (HPLC) analysis of membrane extracts. In cell suspensions, these components were reduced upon addition of formate and oxidized after addition of Cl-OHPA, indicating involvement in organohalide respiration. Genome analysis revealed genes that likely encode the identified components of the electron transport chain from formate to fumarate or Cl-OHPA. Data presented here suggest that the first part of the electron transport chain from formate to fumarate or Cl-OHPA is shared. Electrons are channeled from an outward-facing formate dehydrogenase via menaquinones to a fumarate reductase located at the cytoplasmic face of the membrane. When Cl-OHPA is the terminal electron acceptor, electrons are transferred from menaquinones to outward-facing CprA, via an as-yet-unidentified membrane complex, and potentially an extracellular flavoprotein acting as an electron shuttle between the quinol dehydrogenase membrane complex and CprA. PMID:25512312

The National Environmental Respiratory Center (NERC) experiment in multi-pollutant air quality health research: III. Components of diesel and gasoline engine exhausts, hardwood smoke and simulated downwind coal emissions driving non-cancer biological responses in rodents.

PubMed

Mauderly, Joe L; Seilkop, Steven K

2014-09-01

An approach to identify causal components of complex air pollution mixtures was explored. Rats and mice were exposed by inhalation 6 h daily for 1 week or 6 months to dilutions of simulated downwind coal emissions, diesel and gasoline exhausts and wood smoke. Organ weights, hematology, serum chemistry, bronchoalveolar lavage, central vascular and respiratory allergic responses were measured. Multiple additive regression tree (MART) analysis of the combined database ranked 45 exposure (predictor) variables for importance to models best fitting 47 significant responses. Single-predictor concentration-response data were examined for evidence of single response functions across all exposure groups. Replication of the responses by the combined influences of the two most important predictors was tested. Statistical power was limited by inclusion of only four mixtures, albeit in multiple concentrations each and with particles removed for some groups. Results gave suggestive or strong evidence of causation of 19 of the 47 responses. The top two predictors of the 19 responses included only 12 organic and 6 inorganic species or classes. An increase in red blood cell count of rats by ammonia and pro-atherosclerotic vascular responses of mice by inorganic gases yielded the strongest evidence for causation and the best opportunity for confirmation. The former was a novel finding; the latter was consistent with other results. The results demonstrated the plausibility of identifying putative causal components of highly complex mixtures, given a database in which the ratios of the components are varied sufficiently and exposures and response measurements are conducted using a consistent protocol.

Neural network for photoplethysmographic respiratory rate monitoring

NASA Astrophysics Data System (ADS)

Johansson, Anders

2001-10-01

The photoplethysmographic signal (PPG) includes respiratory components seen as frequency modulation of the heart rate (respiratory sinus arrhythmia, RSA), amplitude modulation of the cardiac pulse, and respiratory induced intensity variations (RIIV) in the PPG baseline. The aim of this study was to evaluate the accuracy of these components in determining respiratory rate, and to combine the components in a neural network for improved accuracy. The primary goal is to design a PPG ventilation monitoring system. PPG signals were recorded from 15 healthy subjects. From these signals, the systolic waveform, diastolic waveform, respiratory sinus arrhythmia, pulse amplitude and RIIV were extracted. By using simple algorithms, the rates of false positive and false negative detection of breaths were calculated for each of the five components in a separate analysis. Furthermore, a simple neural network (NN) was tried out in a combined pattern recognition approach. In the separate analysis, the error rates (sum of false positives and false negatives) ranged from 9.7% (pulse amplitude) to 14.5% (systolic waveform). The corresponding value of the NN analysis was 9.5-9.6%.

Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus.

PubMed

Rincheval, Vincent; Lelek, Mickael; Gault, Elyanne; Bouillier, Camille; Sitterlin, Delphine; Blouquit-Laye, Sabine; Galloux, Marie; Zimmer, Christophe; Eleouet, Jean-François; Rameix-Welti, Marie-Anne

2017-09-15

Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term "IB-associated granules" (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.

A needs assessment to determine the need for respiratory therapy in complex continuing care: A methods paper.

PubMed

Nickerson, Jason W

2015-01-01

There is an emerging demand for complex continuing care for patients who are too ill to safely return home, but for whom hospitalization in an acute care environment is unnecessary or inappropriate. Despite the need and medical complexity of these patients, few respiratory therapists are practising in this environment, and little evidence exists to guide the implementation of respiratory therapy services in this setting. In response to a perceived need for greater respiratory services at Saint Vincent Hospital (Ottawa, Ontario), a needs assessment was undertaken to assess the prevalence of respiratory diseases and for increased respiratory therapist coverage at this complex continuing care hospital. An initial literature review was conducted to guide the assessment, and identified only one tool of relevance, which was obtained and formed the basis of the further development of tools for collecting data at the hospital level and on patient care units at the facility. This needs assessment tool was expanded to include priority areas of relevance that fall within the scope of practice of respiratory therapists, and was supplemented by the analysis of administrative databases and qualitative data gathered through unit walkthroughs and unstructured key informant interviews. A health systems framework was used to structure recommendations for the development of interventions and programs for this patient population. The burden of respiratory disease was significant, and included a high prevalence of inhaled medication and oxygen use, and a significant workload that could be attributed to addressing the respiratory needs of patients. A range of tools and methods are needed to conduct needs assessments for respiratory therapy in complex continuing care. Using multiple data sources, a significant burden of respiratory diseases was present at the Saint Vincent Hospital; further studies in other complex continuing care hospitals are needed to understand the significance of these findings among this patient population more generally.

Effect of hexavalent chromium on electron leakage of respiratory chain in mitochondria isolated from rat liver.

PubMed

Xie, Ying; Zhong, Caigao; Zeng, Ming; Guan, Lan; Luo, Lei

2013-01-01

In the present study, we explored reactive axygen species (ROS) production in mitochondria, the mechanism of hexavalent chromium (Cr(VI)) hepatotoxicity, and the role of protection by GSH. Intact mitochondria were isolated from rat liver tissues and mitochondrial basal respiratory rates of NADH and FADH2 respiratory chains were determined. Mitochondria were treated with Cr(VI), GSH and several complex inhibitors. Mitochondria energized by glutamate/malate were separately or jointly treated with Rotenone (Rot), diphenyleneiodonium (DPI) and antimycinA (Ant), while mitochondria energized by succinate were separately or jointly treated with Rot, DPI ' thenoyltrifluoroacetone (TTFA) and Ant. Cr(VI) concentration-dependently induced ROS production in the NADH and FADH2 respiratory chain in liver mitochondria. Basal respiratory rate of the mitochondrial FADH2 respiratory chain was significantly higher than that of NADH respiratory chain. Hepatic mitochondrial electron leakage induced by Cr(VI) from NADH respiratory chain were mainly from ubiquinone binding sites of complex I and complex III. Treatment with 50µM Cr(VI) enhances forward movement of electrons through FADH2 respiratory chain and leaking through the ubiquinone binding site of complex III. Moreover, the protective effect of GSH on liver mitochondria electron leakage is through removing excess H2O2 and reducing total ROS. Copyright © 2013 S. Karger AG, Basel.

A robust approach for ECG-based analysis of cardiopulmonary coupling.

PubMed

Zheng, Jiewen; Wang, Weidong; Zhang, Zhengbo; Wu, Dalei; Wu, Hao; Peng, Chung-Kang

2016-07-01

Deriving respiratory signal from a surface electrocardiogram (ECG) measurement has advantage of simultaneously monitoring of cardiac and respiratory activities. ECG-based cardiopulmonary coupling (CPC) analysis estimated by heart period variability and ECG-derived respiration (EDR) shows promising applications in medical field. The aim of this paper is to provide a quantitative analysis of the ECG-based CPC, and further improve its performance. Two conventional strategies were tested to obtain EDR signal: R-S wave amplitude and area of the QRS complex. An adaptive filter was utilized to extract the common component of inter-beat interval (RRI) and EDR, generating enhanced versions of EDR signal. CPC is assessed through probing the nonlinear phase interactions between RRI series and respiratory signal. Respiratory oscillations presented in both RRI series and respiratory signals were extracted by ensemble empirical mode decomposition for coupling analysis via phase synchronization index. The results demonstrated that CPC estimated from conventional EDR series exhibits constant and proportional biases, while that estimated from enhanced EDR series is more reliable. Adaptive filtering can improve the accuracy of the ECG-based CPC estimation significantly and achieve robust CPC analysis. The improved ECG-based CPC estimation may provide additional prognostic information for both sleep medicine and autonomic function analysis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

The RNA synthesis machinery of negative-stranded RNA viruses

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

Ortín, Juan, E-mail: jortin@cnb.csic.es; Martín-Benito, Jaime, E-mail: jmartinb@cnb.csic.es

The group of Negative-Stranded RNA Viruses (NSVs) includes many human pathogens, like the influenza, measles, mumps, respiratory syncytial or Ebola viruses, which produce frequent epidemics of disease and occasional, high mortality outbreaks by transmission from animal reservoirs. The genome of NSVs consists of one to several single-stranded, negative-polarity RNA molecules that are always assembled into mega Dalton-sized complexes by association to many nucleoprotein monomers. These RNA-protein complexes or ribonucleoproteins function as templates for transcription and replication by action of the viral RNA polymerase and accessory proteins. Here we review our knowledge on these large RNA-synthesis machines, including the structure ofmore » their components, the interactions among them and their enzymatic activities, and we discuss models showing how they perform the virus transcription and replication programmes. - Highlights: • Overall organisation of NSV RNA synthesis machines. • Structure and function of the ribonucleoprotein components: Atomic structure of the RNA polymerase complex. • Commonalities and differences between segmented- and non-segmented NSVs. • Transcription versus replication programmes.« less

Complexity measures of the central respiratory networks during wakefulness and sleep

NASA Astrophysics Data System (ADS)

Dragomir, Andrei; Akay, Yasemin; Curran, Aidan K.; Akay, Metin

2008-06-01

Since sleep is known to influence respiratory activity we studied whether the sleep state would affect the complexity value of the respiratory network output. Specifically, we tested the hypothesis that the complexity values of the diaphragm EMG (EMGdia) activity would be lower during REM compared to NREM. Furthermore, since REM is primarily generated by a homogeneous population of neurons in the medulla, the possibility that REM-related respiratory output would be less complex than that of the awake state was also considered. Additionally, in order to examine the influence of neuron vulnerabilities within the rostral ventral medulla (RVM) on the complexity of the respiratory network output, we inhibited respiratory neurons in the RVM by microdialysis of GABAA receptor agonist muscimol. Diaphragm EMG, nuchal EMG, EEG, EOG as well as other physiological signals (tracheal pressure, blood pressure and respiratory volume) were recorded from five unanesthetized chronically instrumented intact piglets (3-10 days old). Complexity of the diaphragm EMG (EMGdia) signal during wakefulness, NREM and REM was evaluated using the approximate entropy method (ApEn). ApEn values of the EMGdia during NREM and REM sleep were found significantly (p < 0.05 and p < 0.001, respectively) lower than those of awake EMGdia after muscimol inhibition. In the absence of muscimol, only the differences between REM and wakefulness ApEn values were found to be significantly different.

Glucose Modulates Respiratory Complex I Activity in Response to Acute Mitochondrial Dysfunction

PubMed Central

Cannino, Giuseppe; El-Khoury, Riyad; Pirinen, Marja; Hutz, Bettina; Rustin, Pierre; Jacobs, Howard T.; Dufour, Eric

2012-01-01

Proper coordination between glycolysis and respiration is essential, yet the regulatory mechanisms involved in sensing respiratory chain defects and modifying mitochondrial functions accordingly are unclear. To investigate the nature of this regulation, we introduced respiratory bypass enzymes into cultured human (HEK293T) cells and studied mitochondrial responses to respiratory chain inhibition. In the absence of respiratory chain inhibitors, the expression of alternative respiratory enzymes did not detectably alter cell physiology or mitochondrial function. However, in permeabilized cells NDI1 (alternative NADH dehydrogenase) bypassed complex I inhibition, whereas alternative oxidase (AOX) bypassed complex III or IV inhibition. In contrast, in intact cells the effects of the AOX bypass were suppressed by growth on glucose, whereas those produced by NDI1 were unaffected. Moreover, NDI1 abolished the glucose suppression of AOX-driven respiration, implicating complex I as the target of this regulation. Rapid Complex I down-regulation was partly released upon prolonged respiratory inhibition, suggesting that it provides an “emergency shutdown” system to regulate metabolism in response to dysfunctions of the oxidative phosphorylation. This system was independent of HIF1, mitochondrial superoxide, or ATP synthase regulation. Our findings reveal a novel pathway for adaptation to mitochondrial dysfunction and could provide new opportunities for combatting diseases. PMID:23007390

SIRPα controls the activity of the phagocyte NADPH oxidase by restricting the expression of gp91(phox).

PubMed

van Beek, Ellen M; Zarate, Julian Alvarez; van Bruggen, Robin; Schornagel, Karin; Tool, Anton T J; Matozaki, Takashi; Kraal, Georg; Roos, Dirk; van den Berg, Timo K

2012-10-25

The phagocyte NADPH oxidase mediates oxidative microbial killing in granulocytes and macrophages. However, because the reactive oxygen species produced by the NADPH oxidase can also be toxic to the host, it is essential to control its activity. Little is known about the endogenous mechanism(s) that limits NADPH oxidase activity. Here, we demonstrate that the myeloid-inhibitory receptor SIRPα acts as a negative regulator of the phagocyte NADPH oxidase. Phagocytes isolated from SIRPα mutant mice were shown to have an enhanced respiratory burst. Furthermore, overexpression of SIRPα in human myeloid cells prevented respiratory burst activation. The inhibitory effect required interactions between SIRPα and its natural ligand, CD47, as well as signaling through the SIRPα cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. Suppression of the respiratory burst by SIRPα was caused by a selective repression of gp91(phox) expression, the catalytic component of the phagocyte NADPH oxidase complex. Thus, SIRPα can limit gp91(phox) expression during myeloid development, thereby controlling the magnitude of the respiratory burst in phagocytes. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

Rényi entropy and Lempel-Ziv complexity of mechanomyographic recordings of diaphragm muscle as indexes of respiratory effort.

PubMed

Torres, Abel; Fiz, Jose A; Jane, Raimon; Laciar, Eric; Galdiz, Juan B; Gea, Joaquim; Morera, Josep

2008-01-01

The study of the mechanomyographic (MMG) signals of respiratory muscles is a promising technique in order to evaluate the respiratory muscles effort. A new approach for quantifying the relationship between respiratory MMG signals and respiratory effort is presented by analyzing the spatio-temporal patterns in the MMG signal using two non-linear methods: Rényi entropy and Lempel-Ziv (LZ) complexity analysis. Both methods are well suited to the analysis of non-stationary biomedical signals of short length. In this study, MMG signals of the diaphragm muscle acquired by means of a capacitive accelerometer applied on the costal wall were analyzed. The method was tested on an animal model (dogs), and the diaphragmatic MMG signal was recorded continuously while two non anesthetized mongrel dogs performed a spontaneous ventilation protocol with an incremental inspiratory load. The performance in discriminating high and low respiratory effort levels with these two methods was analyzed with the evaluation of the Pearson correlation coefficient between the MMG parameters and respiratory effort parameters extracted from the inspiratory pressure signal. The results obtained show an increase of the MMG signal Rényi entropy and LZ complexity values with the increase of the respiratory effort. Compared with other parameters analyzed in previous works, both Rényi entropy and LZ complexity indexes demonstrates better performance in all the signals analyzed. Our results suggest that these non-linear techniques are useful to detect and quantify changes in the respiratory effort by analyzing MMG respiratory signals.

Four-dimensional computed tomography based respiratory-gated radiotherapy with respiratory guidance system: analysis of respiratory signals and dosimetric comparison.

PubMed

Lee, Jung Ae; Kim, Chul Yong; Yang, Dae Sik; Yoon, Won Sup; Park, Young Je; Lee, Suk; Kim, Young Bum

2014-01-01

To investigate the effectiveness of respiratory guidance system in 4-dimensional computed tomography (4 DCT) based respiratory-gated radiation therapy (RGRT) by comparing respiratory signals and dosimetric analysis of treatment plans. The respiratory amplitude and period of the free, the audio device-guided, and the complex system-guided breathing were evaluated in eleven patients with lung or liver cancers. The dosimetric parameters were assessed by comparing free breathing CT plan and 4 DCT-based 30-70% maximal intensity projection (MIP) plan. The use of complex system-guided breathing showed significantly less variation in respiratory amplitude and period compared to the free or audio-guided breathing regarding the root mean square errors (RMSE) of full inspiration (P = 0.031), full expiration (P = 0.007), and period (P = 0.007). The dosimetric parameters including V(5 Gy), V(10 Gy), V(20 Gy), V(30 Gy), V(40 Gy), and V(50 Gy) of normal liver or lung in 4 DCT MIP plan were superior over free breathing CT plan. The reproducibility and regularity of respiratory amplitude and period were significantly improved with the complex system-guided breathing compared to the free or the audio-guided breathing. In addition, the treatment plan based on the 4D CT-based MIP images acquired with the complex system guided breathing showed better normal tissue sparing than that on the free breathing CT.

[Detection of respiratory tract diseases among rural population during the team-work mass screening].

PubMed

Abramson, E Z; Galkin, V B; Stepanova, G Ia

1990-01-01

A screening complex for the examination of the rural population has been worked out to detect bronchopulmonary pathology and form groups of risk for respiratory diseases. The complex of methods included compulsory questionnaires and ++fluoro-functional examination, spirometry if indicated and bacterial tests. Out of 1, 131 persons examined, 328 were found to have respiratory diseases. Chronic non-specific respiratory diseases were detected in 103 subjects, including 62 of them having obstructive bronchitis. A risk group developing chronic non-specific respiratory diseases, including 202 persons with disturbed ventilation activity of the lungs, post-tuberculous inadequate changes and other pathology. Pulmonary tuberculosis was registered in 7 subjects. The given data indicate the necessity of a complex examination of the population.

Acute effects on cardiovascular oscillations during controlled slow yogic breathing.

PubMed

Bhagat, Om Lata; Kharya, Chhaya; Jaryal, Ashok; Deepak, Kishore Kumar

2017-04-01

Breathing exercises are believed to modulate the cardiovascular oscillations in the body. To assess the validity of the assumption and understand the underlying mechanism, the key autonomic regulatory parameters such as heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were recorded during controlled slow yogic breathing. Alternate nostril breathing (ANB) was selected as the yogic manoeuvre. Twelve healthy volunteers (age 30±3.8 yr) participated in the study. ANB was performed at a breathing frequency of 5 breaths per minute (bpm). In each participant, the electrocardiogram, respiratory movements, beat-to-beat BP and end-tidal carbon dioxide were recorded for five minutes each: before, during and after ANB. The records were analyzed for HRV, BPV and BRS. During ANB, HRV analysis showed significant increase in the standard deviation of all NN intervals, low-frequency (LF) component, LF/HF (low frequency/high frequency) ratio and significant decrease in the HF component. BPV analysis showed a significant increase in total power in systolic BPV (SBPV), diastolic BPV (DBPV) and mean BPV. BRS analysis showed a significant increase in the total number of sequences in SBPV and DBPV and significant augmentation of α-LF and reduction in α-HF. The power spectrum showed a dominant peak in HRV at 0.08 Hz (LF component) similar to the respiratory frequency. The acute short-term change in circulatory control system declined immediately after the cessation of slow yogic breathing (ANB) and remained elevated in post-ANB stage as compared to the pre-ANB. Significant increase in cardiovascular oscillations and baroreflex recruitments during-ANB suggested a dynamic interaction between respiratory and cardiovascular system. Enhanced phasic relationship with some delay indicated the complexity of the system. It indicated that respiratory and cardiovascular oscillations were coupled through multiple regulatory mechanisms, such as mechanical coupling, baroreflex and central cardiovascular control.

Analysis of a dielectric EAP as smart component for a neonatal respiratory simulator.

PubMed

Tognarelli, S; Deri, L; Cecchi, F; Scaramuzzo, R; Cuttano, A; Laschi, C; Menciassi, A; Dario, P

2013-01-01

Nowadays, respiratory syndrome represents the most common neonatal pathology. Nevertheless, being respiratory assistance in newborns a great challenge for neonatologists and nurses, use of simulation-based training is quickly becoming a valid meaning of clinical education for an optimal therapy outcome. Commercially available simulators, are, however, not able to represent complex breathing patterns and to evaluate specific alterations. The purpose of this work has been to develop a smart, lightweight, compliant system with variable rigidity able to replicate the anatomical behavior of the neonatal lung, with the final aim to integrate such system into an innovative mechatronic simulator device. A smart material based-system has been proposed and validated: Dielectric Electro Active Polymers (DEAP), coupled to a purposely shaped silicone camera, has been investigated as active element for a compliance change simulator able to replicate both physiological and pathological lung properties. Two different tests have been performed by using a bi-components camera (silicone shape coupled to PolyPower film) both as an isolated system and connected to an infant ventilator. By means of a pressure sensor held on the silicon structure, pressure values have been collected and compared for active and passive PolyPower working configuration. The obtained results confirm a slight pressure decrease in active configuration, that is in agreement with the film stiffness reduction under activation and demonstrates the real potentiality of DEAP for active volume changing of the proposed system.

Effect of Age on Complexity and Causality of the Cardiovascular Control: Comparison between Model-Based and Model-Free Approaches

PubMed Central

Porta, Alberto; Faes, Luca; Bari, Vlasta; Marchi, Andrea; Bassani, Tito; Nollo, Giandomenico; Perseguini, Natália Maria; Milan, Juliana; Minatel, Vinícius; Borghi-Silva, Audrey; Takahashi, Anielle C. M.; Catai, Aparecida M.

2014-01-01

The proposed approach evaluates complexity of the cardiovascular control and causality among cardiovascular regulatory mechanisms from spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and respiration (RESP). It relies on construction of a multivariate embedding space, optimization of the embedding dimension and a procedure allowing the selection of the components most suitable to form the multivariate embedding space. Moreover, it allows the comparison between linear model-based (MB) and nonlinear model-free (MF) techniques and between MF approaches exploiting local predictability (LP) and conditional entropy (CE). The framework was applied to study age-related modifications of complexity and causality in healthy humans in supine resting (REST) and during standing (STAND). We found that: 1) MF approaches are more efficient than the MB method when nonlinear components are present, while the reverse situation holds in presence of high dimensional embedding spaces; 2) the CE method is the least powerful in detecting age-related trends; 3) the association of HP complexity on age suggests an impairment of cardiac regulation and response to STAND; 4) the relation of SAP complexity on age indicates a gradual increase of sympathetic activity and a reduced responsiveness of vasomotor control to STAND; 5) the association from SAP to HP on age during STAND reveals a progressive inefficiency of baroreflex; 6) the reduced connection from HP to SAP with age might be linked to the progressive exploitation of Frank-Starling mechanism at REST and to the progressive increase of peripheral resistances during STAND; 7) at REST the diminished association from RESP to HP with age suggests a vagal withdrawal and a gradual uncoupling between respiratory activity and heart; 8) the weakened connection from RESP to SAP with age might be related to the progressive increase of left ventricular thickness and vascular stiffness and to the gradual decrease of respiratory sinus arrhythmia. PMID:24586796

Neurokinin receptor modulation of respiratory activity in the rabbit.

PubMed

Bongianni, Fulvia; Mutolo, Donatella; Cinelli, Elenia; Pantaleo, Tito

2008-06-01

The respiratory role of neurokinin (NK) receptors was investigated in alpha-chloralose-urethane-anaesthetized, vagotomized, paralysed and artificially ventilated rabbits by using bilateral microinjections (30-50 nL) of NK receptor agonists and antagonists. Microinjections were performed in a region located just caudal to the rostral expiratory neurons. This region displayed features similar to those of the pre-Bötzinger complex (pre-BötC) of adult cats and rats, and proved to produce excitatory respiratory effects in response to microinjections of D,L-homocysteic acid. We used as agonists (0.1, 0.5 and 5 mM) substance P (SP), the NK1 receptor agonists [Sar(9), Met(O2)(11)]-SP and GR 73632, the NK2 receptor agonist NKA, the NK3 receptor agonist senktide, and as antagonists (5 mM) the NK1 receptor antagonist CP-99,994 and the NK2 receptor antagonist MEN 10376. SP always increased respiratory frequency, but NK1 receptor agonists did not change respiratory variables. NKA and senktide at 5 mm increased respiratory frequency. CP-99,994 caused increases in respiratory frequency and did not antagonize the effects of SP. MEN 10376 prevented the respiratory responses induced by NKA and reduced those provoked by SP. SP or the NK1 receptor agonists (5 mM) injected (1 microL) into the IV ventricle caused marked excitatory effects on respiration. The results suggest that NK2 and NK3, but not NK1, receptors are involved in the excitatory modulation of inspiratory activity within the investigated region and are consistent with the notion that the pre-BötC neurons are important components of the inspiratory rhythm-generating mechanisms.

Multistate Lempel-Ziv (MLZ) index interpretation as a measure of amplitude and complexity changes.

PubMed

Sarlabous, Leonardo; Torres, Abel; Fiz, Jose A; Gea, Joaquim; Galdiz, Juan B; Jane, Raimon

2009-01-01

The Lempel-Ziv complexity (LZ) has been widely used to evaluate the randomness of finite sequences. In general, the LZ complexity has been used to determine the complexity grade present in biomedical signals. The LZ complexity is not able to discern between signals with different amplitude variations and similar random components. On the other hand, amplitude parameters, as the root mean square (RMS), are not able to discern between signals with similar power distributions and different random components. In this work, we present a novel method to quantify amplitude and complexity variations in biomedical signals by means of the computation of the LZ coefficient using more than two quantification states, and with thresholds fixed and independent of the dynamic range or standard deviation of the analyzed signal: the Multistate Lempel-Ziv (MLZ) index. Our results indicate that MLZ index with few quantification levels only evaluate the complexity changes of the signal, with high number of levels, the amplitude variations, and with an intermediate number of levels informs about both amplitude and complexity variations. The study performed in diaphragmatic mechanomyographic signals shows that the amplitude variations of this signal are more correlated with the respiratory effort than the complexity variations. Furthermore, it has been observed that the MLZ index with high number of levels practically is not affected by the existence of impulsive, sinusoidal, constant and Gaussian noises compared with the RMS amplitude parameter.

The bacterial flagellar switch complex is getting more complex

PubMed Central

Cohen-Ben-Lulu, Galit N; Francis, Noreen R; Shimoni, Eyal; Noy, Dror; Davidov, Yaacov; Prasad, Krishna; Sagi, Yael; Cecchini, Gary; Johnstone, Rose M; Eisenbach, Michael

2008-01-01

The mechanism of function of the bacterial flagellar switch, which determines the direction of flagellar rotation and is essential for chemotaxis, has remained an enigma for many years. Here we show that the switch complex associates with the membrane-bound respiratory protein fumarate reductase (FRD). We provide evidence that FRD binds to preparations of isolated switch complexes, forms a 1:1 complex with the switch protein FliG, and that this interaction is required for both flagellar assembly and switching the direction of flagellar rotation. We further show that fumarate, known to be a clockwise/switch factor, affects the direction of flagellar rotation through FRD. These results not only uncover a new component important for switching and flagellar assembly, but they also reveal that FRD, an enzyme known to be primarily expressed and functional under anaerobic conditions in Escherichia coli, nonetheless, has important, unexpected functions under aerobic conditions. PMID:18337747

NADH-ubiquinone oxidoreductase activity in the kinetoplasts of the plant trypanosomatid Phytomonas serpens.

PubMed

González-Halphen, Diego; Maslov, Dmitri A

2004-03-01

NADH-ubiquinone oxidoreductase activity is present in mitochondrial lysates of Phytomonas serpens. Rotenone at 2-10 microM inhibited the activity 50-75%, indicating that it belongs to respiratory complex I. The activity was also inhibited 50-60% in the presence of 10-30 nM atovaquone suggesting that inhibition of complex I represents a likely mechanism of the known antileishmanial activity of this drug. The complex was partially purified by chromatography on DEAE-Sepharose CL-6B and gel-filtration on Sepharose CL-2B. The NADH:ubiquinone oxidoreductase activity in this preparation was completely inactivated by 20 nM atovaquone. The partially purified complex was present in a low amount and its subunits could not be discerned by staining with Coomassie. However, one of its components, a homologue of the 39 kDa subunit of the bovine complex I, was identified immunochemically in the original lysate and in the partially purified material.

A nonlinear circuit architecture for magnetoencephalographic signal analysis.

PubMed

Bucolo, M; Fortuna, L; Frasca, M; La Rosa, M; Virzì, M C; Shannahoff-Khalsa, D

2004-01-01

The objective of this paper was to face the complex spatio-temporal dynamics shown by Magnetoencephalography (MEG) data by applying a nonlinear distributed approach for the Blind Sources Separation. The effort was to characterize and differ-entiate the phases of a yogic respiratory exercise used in the treatment of obsessive compulsive disorders. The patient performed a precise respiratory protocol, at one breath per minute for 31 minutes, with 10 minutes resting phase before and after. The two steps of classical Independent Component Approach have been performed by using a Cellular Neural Network with two sets of templates. The choice of the couple of suitable templates has been carried out using genetic algorithm optimization techniques. Performing BSS with a nonlinear distributed approach, the outputs of the CNN have been compared to the ICA ones. In all the protocol phases, the main components founded with CNN have similar trends compared with that ones obtained with ICA. Moreover, using this distributed approach, a spatial location has been associated to each component. To underline the spatio-temporal and the nonlinearly of the neural process a distributed nonlinear architecture has been proposed. This strategy has been designed in order to overcome the hypothesis of linear combination among the sources signals, that is characteristic of the ICA approach, taking advantage of the spatial information.

Mitochondrial respiratory chain complexes as sources and targets of thiol-based redox-regulation.

PubMed

Dröse, Stefan; Brandt, Ulrich; Wittig, Ilka

2014-08-01

The respiratory chain of the inner mitochondrial membrane is a unique assembly of protein complexes that transfers the electrons of reducing equivalents extracted from foodstuff to molecular oxygen to generate a proton-motive force as the primary energy source for cellular ATP-synthesis. Recent evidence indicates that redox reactions are also involved in regulating mitochondrial function via redox-modification of specific cysteine-thiol groups in subunits of respiratory chain complexes. Vice versa the generation of reactive oxygen species (ROS) by respiratory chain complexes may have an impact on the mitochondrial redox balance through reversible and irreversible thiol-modification of specific target proteins involved in redox signaling, but also pathophysiological processes. Recent evidence indicates that thiol-based redox regulation of the respiratory chain activity and especially S-nitrosylation of complex I could be a strategy to prevent elevated ROS production, oxidative damage and tissue necrosis during ischemia-reperfusion injury. This review focuses on the thiol-based redox processes involving the respiratory chain as a source as well as a target, including a general overview on mitochondria as highly compartmentalized redox organelles and on methods to investigate the redox state of mitochondrial proteins. This article is part of a Special Issue entitled: Thiol-Based Redox Processes. Copyright © 2014 Elsevier B.V. All rights reserved.

Self-Reported Mental Health Predicts Acute Respiratory Infection.

PubMed

Maxwell, Lizzie; Barrett, Bruce; Chase, Joseph; Brown, Roger; Ewers, Tola

2015-06-01

Poor mental health conditions, including stress and depression, have been recognized as a risk factor for the development of acute respiratory infection. Very few studies have considered the role of general mental health in acute respiratory infection occurrence. The aim of this analysis is to determine if overall mental health, as assessed by the mental component of the Short Form 12 Health Survey, predicts incidence, duration, or severity of acute respiratory infection. Data utilized for this analysis came from the National Institute of Health-funded Meditation or Exercise for Preventing Acute Respiratory Infection (MEPARI) and MEPARI-2 randomized controlled trials examining the effects of meditation or exercise on acute respiratory infection among adults aged > 30 years in Madison, Wisconsin. A Kendall tau rank correlation compared the Short Form 12 mental component, completed by participants at baseline, with acute respiratory infection incidence, duration, and area-under-the-curve (global) severity, as assessed by the Wisconsin Upper Respiratory Symptom Survey. Participants were recruited from Madison, Wis, using advertisements in local media. Short Form 12 mental health scores significantly predicted incidence (P = 0.037) of acute respiratory infection, but not duration (P = 0.077) or severity (P = 0.073). The Positive and Negative Affect Schedule (PANAS) negative emotion measure significantly predicted global severity (P = 0.036), but not incidence (P = 0.081) or duration (P = 0.125). Mindful Attention Awareness Scale scores significantly predicted incidence of acute respiratory infection (P = 0.040), but not duration (P = 0.053) or severity (P = 0.70). The PHQ-9, PSS-10, and PANAS positive measures did not show significant predictive associations with any of the acute respiratory infection outcomes. Self-reported overall mental health, as measured by the mental component of Short Form 12, predicts acute respiratory infection incidence.

Myoglobin and the regulation of mitochondrial respiratory chain complex IV.

PubMed

Yamada, Tatsuya; Takakura, Hisashi; Jue, Thomas; Hashimoto, Takeshi; Ishizawa, Rie; Furuichi, Yasuro; Kato, Yukio; Iwanaka, Nobumasa; Masuda, Kazumi

2016-01-15

Mitochondrial respiration is regulated by multiple elaborate mechanisms. It has been shown that muscle specific O2 binding protein, Myoglobin (Mb), is localized in mitochondria and interacts with respiratory chain complex IV, suggesting that Mb could be a factor that regulates mitochondrial respiration. Here, we demonstrate that muscle mitochondrial respiration is improved by Mb overexpression via up-regulation of complex IV activity in cultured myoblasts; in contrast, suppression of Mb expression induces a decrease in complex IV activity and mitochondrial respiration compared with the overexpression model. The present data are the first to show the biological significance of mitochondrial Mb as a potential modulator of mitochondrial respiratory capacity. Mitochondria are important organelles for metabolism, and their respiratory capacity is a primary factor in the regulation of energy expenditure. Deficiencies of cytochrome c oxidase complex IV, which reduces O2 in mitochondria, are linked to several diseases, such as mitochondrial myopathy. Moreover, mitochondrial respiration in skeletal muscle tissue tends to be susceptible to complex IV activity. Recently, we showed that the muscle-specific protein myoglobin (Mb) interacts with complex IV. The precise roles of mitochondrial Mb remain unclear. Here, we demonstrate that Mb facilitates mitochondrial respiratory capacity in skeletal muscles. Although mitochondrial DNA copy numbers were not altered in Mb-overexpressing myotubes, O2 consumption was greater in these myotubes than that in mock cells (Mock vs. Mb-Flag::GFP: state 4, 1.00 ± 0.09 vs. 1.77 ± 0.34; state 3, 1.00 ± 0.29; Mock: 1.60 ± 0.53; complex 2-3-4: 1.00 ± 0.30 vs. 1.50 ± 0.44; complex IV: 1.00 ± 0.14 vs. 1.87 ± 0.27). This improvement in respiratory capacity could be because of the activation of enzymatic activity of respiratory complexes. Moreover, mitochondrial respiration was up-regulated in myoblasts transiently overexpressing Mb; complex IV activity was solely activated in Mb-overexpressing myoblasts, and complex IV activity was decreased in the myoblasts in which Mb expression was suppressed by Mb-siRNA transfection (Mb vector transfected vs. Mb vector, control siRNA transfected vs. Mb vector, Mb siRNA transfected: 0.15 vs. 0.15 vs. 0.06). Therefore, Mb enhances the enzymatic activity of complex IV to ameliorate mitochondrial respiratory capacity, and could play a pivotal role in skeletal muscle metabolism. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS)

PubMed Central

Mahdavinia, Mahboobeh; Keshavarzian, Ali; Tobin, Mary C; Landay, Alan; Schleimer, Robert P.

2015-01-01

Chronic rhinosinusitis (CRS) has been known as a disease with strong infectious and inflammatory components for decades. The recent advancement in methods identifying microbes has helped implicate the airway microbiome in inflammatory respiratory diseases such as asthma and COPD. Such studies support a role of resident microbes in both health and disease of host tissue, especially in the case of inflammatory mucosal diseases. Identifying interactive events between microbes and elements of the immune system can help us to uncover the pathogenic mechanisms underlying chronic rhinosinusitis. Here we provide a review of the findings on the complex upper respiratory microbiome in CRS in comparison to healthy controls. Furthermore, we have reviewed the defects and alterations of the host immune system that interact with microbes and could be associated with dysbiosis in CRS. PMID:26510171

A synthetic computational environment: To control the spread of respiratory infections in a virtual university

NASA Astrophysics Data System (ADS)

Ge, Yuanzheng; Chen, Bin; liu, Liang; Qiu, Xiaogang; Song, Hongbin; Wang, Yong

2018-02-01

Individual-based computational environment provides an effective solution to study complex social events by reconstructing scenarios. Challenges remain in reconstructing the virtual scenarios and reproducing the complex evolution. In this paper, we propose a framework to reconstruct a synthetic computational environment, reproduce the epidemic outbreak, and evaluate management interventions in a virtual university. The reconstructed computational environment includes 4 fundamental components: the synthetic population, behavior algorithms, multiple social networks, and geographic campus environment. In the virtual university, influenza H1N1 transmission experiments are conducted, and gradually enhanced interventions are evaluated and compared quantitatively. The experiment results indicate that the reconstructed virtual environment provides a solution to reproduce complex emergencies and evaluate policies to be executed in the real world.

Is there a genetic solution to bovine respiratory disease complex?

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a complex multi-factor disease, which increases costs and reduces revenue from feedlot cattle. Multiple stressors and pathogens (viral and bacterial) have been implicated in the etiology of BRDC, therefore multiple approaches will be needed to evaluate a...

Proteomic and computational analysis of bronchoalveolar proteins during the course of the acute respiratory distress syndrome.

PubMed

Chang, Dong W; Hayashi, Shinichi; Gharib, Sina A; Vaisar, Tomas; King, S Trevor; Tsuchiya, Mitsuhiro; Ruzinski, John T; Park, David R; Matute-Bello, Gustavo; Wurfel, Mark M; Bumgarner, Roger; Heinecke, Jay W; Martin, Thomas R

2008-10-01

Acute lung injury causes complex changes in protein expression in the lungs. Whereas most prior studies focused on single proteins, newer methods allowing the simultaneous study of many proteins could lead to a better understanding of pathogenesis and new targets for treatment. The purpose of this study was to examine the changes in protein expression in the bronchoalveolar lavage fluid (BALF) of patients during the course of the acute respiratory distress syndrome (ARDS). Using two-dimensional difference gel electrophoresis (DIGE), the expression of proteins in the BALF from patients on Days 1 (n = 7), 3 (n = 8), and 7 (n = 5) of ARDS were compared with findings in normal volunteers (n = 9). The patterns of protein expression were analyzed using principal component analysis (PCA). Biological processes that were enriched in the BALF proteins of patients with ARDS were identified using Gene Ontology (GO) analysis. Protein networks that model the protein interactions in the BALF were generated using Ingenuity Pathway Analysis. An average of 991 protein spots were detected using DIGE. Of these, 80 protein spots, representing 37 unique proteins in all of the fluids, were identified using mass spectrometry. PCA confirmed important differences between the proteins in the ARDS and normal samples. GO analysis showed that these differences are due to the enrichment of proteins involved in inflammation, infection, and injury. The protein network analysis showed that the protein interactions in ARDS are complex and redundant, and revealed unexpected central components in the protein networks. Proteomics and protein network analysis reveals the complex nature of lung protein interactions in ARDS. The results provide new insights about protein networks in injured lungs, and identify novel mediators that are likely to be involved in the pathogenesis and progression of acute lung injury.

Crystallization of Mitochondrial Respiratory Complex II from Chicken Heart: a Membrane Protein Complex Diffracting to 2.0 Å.

PubMed Central

Huang, Li-shar; Borders, Toni M.; Shen, John T.; Wang, Chung-Jen; Berry, Edward

2006-01-01

Synopsis A multi-subunit mitochondrial membrane protein complex involved in the Krebs Cycle and respiratory chain has been crystallized in a form suitable for near-atomic resolution structure determination. A procedure is presented for preparation of diffraction-quality crystals of a vertebrate mitochondrial respiratory Complex II. The crystals have the potential to diffract to at least 2.0 Å with optimization of post-crystal-growth treatment and cryoprotection. This should allow determination of the structure of this important and medically relevant membrane protein complex at near-atomic resolution and provide great detail of the mode of binding of substrates and inhibitors at the two substrate-binding sites. PMID:15805592

Instantaneous Respiratory Estimation from Thoracic Impedance by Empirical Mode Decomposition.

PubMed

Wang, Fu-Tai; Chan, Hsiao-Lung; Wang, Chun-Li; Jian, Hung-Ming; Lin, Sheng-Hsiung

2015-07-07

Impedance plethysmography provides a way to measure respiratory activity by sensing the change of thoracic impedance caused by inspiration and expiration. This measurement imposes little pressure on the body and uses the human body as the sensor, thereby reducing the need for adjustments as body position changes and making it suitable for long-term or ambulatory monitoring. The empirical mode decomposition (EMD) can decompose a signal into several intrinsic mode functions (IMFs) that disclose nonstationary components as well as stationary components and, similarly, capture respiratory episodes from thoracic impedance. However, upper-body movements usually produce motion artifacts that are not easily removed by digital filtering. Moreover, large motion artifacts disable the EMD to decompose respiratory components. In this paper, motion artifacts are detected and replaced by the data mirrored from the prior and the posterior before EMD processing. A novel intrinsic respiratory reconstruction index that considers both global and local properties of IMFs is proposed to define respiration-related IMFs for respiration reconstruction and instantaneous respiratory estimation. Based on the experiments performing a series of static and dynamic physical activates, our results showed the proposed method had higher cross correlations between respiratory frequencies estimated from thoracic impedance and those from oronasal airflow based on small window size compared to the Fourier transform-based method.

Instantaneous Respiratory Estimation from Thoracic Impedance by Empirical Mode Decomposition

PubMed Central

Wang, Fu-Tai; Chan, Hsiao-Lung; Wang, Chun-Li; Jian, Hung-Ming; Lin, Sheng-Hsiung

2015-01-01

Impedance plethysmography provides a way to measure respiratory activity by sensing the change of thoracic impedance caused by inspiration and expiration. This measurement imposes little pressure on the body and uses the human body as the sensor, thereby reducing the need for adjustments as body position changes and making it suitable for long-term or ambulatory monitoring. The empirical mode decomposition (EMD) can decompose a signal into several intrinsic mode functions (IMFs) that disclose nonstationary components as well as stationary components and, similarly, capture respiratory episodes from thoracic impedance. However, upper-body movements usually produce motion artifacts that are not easily removed by digital filtering. Moreover, large motion artifacts disable the EMD to decompose respiratory components. In this paper, motion artifacts are detected and replaced by the data mirrored from the prior and the posterior before EMD processing. A novel intrinsic respiratory reconstruction index that considers both global and local properties of IMFs is proposed to define respiration-related IMFs for respiration reconstruction and instantaneous respiratory estimation. Based on the experiments performing a series of static and dynamic physical activates, our results showed the proposed method had higher cross correlations between respiratory frequencies estimated from thoracic impedance and those from oronasal airflow based on small window size compared to the Fourier transform-based method. PMID:26198231

Respiratory mechanics in infants with severe bronchiolitis on controlled mechanical ventilation.

PubMed

Cruces, Pablo; González-Dambrauskas, Sebastián; Quilodrán, Julio; Valenzuela, Jorge; Martínez, Javier; Rivero, Natalia; Arias, Pablo; Díaz, Franco

2017-10-06

Analysis of respiratory mechanics during mechanical ventilation (MV) is able to estimate resistive, elastic and inertial components of the working pressure of the respiratory system. Our aim was to discriminate the components of the working pressure of the respiratory system in infants on MV with severe bronchiolitis admitted to two PICU's. Infants younger than 1 year old with acute respiratory failure caused by severe bronchiolitis underwent neuromuscular blockade, tracheal intubation and volume controlled MV. Shortly after intubation studies of pulmonary mechanics were performed using inspiratory and expiratory breath hold. The maximum inspiratory and expiratory flow (QI and QE) as well as peak inspiratory (PIP), plateau (PPL) and total expiratory pressures (tPEEP) were measured. Inspiratory and expiratory resistances (RawI and RawE) and Time Constants (K TI and K TE ) were calculated. We included 16 patients, of median age 2.5 (1-5.8) months. Bronchiolitis due to respiratory syncytial virus was the main etiology (93.8%) and 31.3% had comorbidities. Measured respiratory pressures were PIP 29 (26-31), PPL 24 (20-26), tPEEP 9 [8-11] cmH2O. Elastic component of the working pressure was significantly higher than resistive and both higher than threshold (tPEEP - PEEP) (P < 0.01). QI was significantly lower than QE [5 (4.27-6.75) v/s 16.5 (12-23.8) L/min. RawI and RawE were 38.8 (32-53) and 40.5 (22-55) cmH2O/L/s; K TI and K TE [0.18 (0.12-0.30) v/s 0.18 (0.13-0.22) s], and K TI :K TE ratio was 1:1.04 (1:0.59-1.42). Analysis of respiratory mechanics of infants with severe bronchiolitis receiving MV shows that the elastic component of the working pressure of the respiratory system is the most important. The elastic and resistive components in conjunction with flow profile are characteristic of restrictive diseases. A better understanding of lung mechanics in this group of patients may lead to change the traditional ventilatory approach to severe bronchiolitis.

Components of Diesel Exhaust Particles Diversely Enhance a Variety of Respiratory Diseases Related to Infection or Allergy: Extracted Organic Chemicals and the Residual Particles after Extraction Differently Affect Respiratory Diseases

PubMed Central

Takano, Hirohisa; Yanagisawa, Rie; Inoue, Ken-ichiro

2007-01-01

Experimental and epidemiological studies have reported that diesel exhaust particles (DEP) can aggravate a variety of respiratory diseases including infection or allergy. However, the responsible components in DEP for the enhancement have not been identified. The present review demonstrates the different effects of the components of DEP on the respiratory diseases related to infection or allergy. We exposed mice to the organic chemicals (DEP-OC) and the residual carbonaceous nuclei (washed DEP) derived from DEP in the presence or absence of bacterial endotoxin (lipopolysaccharide: LPS) or allergen. In our first series of experiments, washed DEP combined with LPS synergistically exacerbated lung injury, which was concomitant with the enhanced lung expression of proinflammatory cytokines and chemokines, whereas DEP-OC combined with LPS did not. In contrast, our second series of experiments showed that DEP-OC, rather than washed DEP, enhanced allergen-related eosinophilic inflammation and proliferation of goblet cells in the airway epithelium, which was paralleled by the enhanced lung expression of eotaxin and interleukin-5. However, washed DEP with ovalbmin showed less change and increased the lung expression of interferon-γ. It is suggested that DEP components diversely affect various types of respiratory diseases, while the combination of organic chemicals and carbonaceous nuclei (whole DEP) mostly aggravate respiratory diseases. PMID:18188411

The Epidemiology of Transfusion-related Acute Lung Injury Varies According to the Applied Definition of Lung Injury Onset Time.

PubMed

Vande Vusse, Lisa K; Caldwell, Ellen; Tran, Edward; Hogl, Laurie; Dinwiddie, Steven; López, José A; Maier, Ronald V; Watkins, Timothy R

2015-09-01

Research that applies an unreliable definition for transfusion-related acute lung injury (TRALI) may draw false conclusions about its risk factors and biology. The effectiveness of preventive strategies may decrease as a consequence. However, the reliability of the consensus TRALI definition is unknown. To prospectively study the effect of applying two plausible definitions of acute respiratory distress syndrome onset time on TRALI epidemiology. We studied 316 adults admitted to the intensive care unit and transfused red blood cells within 24 hours of blunt trauma. We identified patients with acute respiratory distress syndrome, and defined acute respiratory distress syndrome onset time two ways: (1) the time at which the first radiographic or oxygenation criterion was met, and (2) the time both criteria were met. We categorized two corresponding groups of TRALI cases transfused in the 6 hours before acute respiratory distress syndrome onset. We used Cohen's kappa to measure agreement between the TRALI cases and implicated blood components identified by the two acute respiratory distress syndrome onset time definitions. In a nested case-control study, we examined potential risk factors for each group of TRALI cases, including demographics, injury severity, and characteristics of blood components transfused in the 6 hours before acute respiratory distress syndrome onset. Forty-two of 113 patients with acute respiratory distress syndrome were TRALI cases per the first acute respiratory distress syndrome onset time definition and 63 per the second definition. There was slight agreement between the two groups of TRALI cases (κ = 0.16; 95% confidence interval, -0.01 to 0.33) and between the implicated blood components (κ = 0.15, 95% confidence interval, 0.11-0.20). Age, Injury Severity Score, high plasma-volume components, and transfused plasma volume were risk factors for TRALI when applying the second acute respiratory distress syndrome onset time definition but not when applying the first definition. The epidemiology of TRALI varies when applying two plausible definitions of acute respiratory distress syndrome onset time to severely injured trauma patients. A TRALI definition that standardizes acute respiratory distress syndrome onset time might improve reliability and align efforts to understand epidemiology, biology, and prevention.

Crystal structure of mitochondrial respiratory membrane protein complex II.

PubMed

Sun, Fei; Huo, Xia; Zhai, Yujia; Wang, Aojin; Xu, Jianxing; Su, Dan; Bartlam, Mark; Rao, Zihe

2005-07-01

The mitochondrial respiratory Complex II or succinate:ubiquinone oxidoreductase (SQR) is an integral membrane protein complex in both the tricarboxylic acid cycle and aerobic respiration. Here we report the first crystal structure of Complex II from porcine heart at 2.4 A resolution and its complex structure with inhibitors 3-nitropropionate and 2-thenoyltrifluoroacetone (TTFA) at 3.5 A resolution. Complex II is comprised of two hydrophilic proteins, flavoprotein (Fp) and iron-sulfur protein (Ip), and two transmembrane proteins (CybL and CybS), as well as prosthetic groups required for electron transfer from succinate to ubiquinone. The structure correlates the protein environments around prosthetic groups with their unique midpoint redox potentials. Two ubiquinone binding sites are discussed and elucidated by TTFA binding. The Complex II structure provides a bona fide model for study of the mitochondrial respiratory system and human mitochondrial diseases related to mutations in this complex.

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…

Chemicals or mutations that target mitochondrial translation can rescue the respiratory deficiency of yeast bcs1 mutants.

PubMed

Panozzo, C; Laleve, A; Tribouillard-Tanvier, D; Ostojić, J; Sellem, C H; Friocourt, G; Bourand-Plantefol, A; Burg, A; Delahodde, A; Blondel, M; Dujardin, G

2017-12-01

Bcs1p is a chaperone that is required for the incorporation of the Rieske subunit within complex III of the mitochondrial respiratory chain. Mutations in the human gene BCS1L (BCS1-like) are the most frequent nuclear mutations resulting in complex III-related pathologies. In yeast, the mimicking of some pathogenic mutations causes a respiratory deficiency. We have screened chemical libraries and found that two antibiotics, pentamidine and clarithromycin, can compensate two bcs1 point mutations in yeast, one of which is the equivalent of a mutation found in a human patient. As both antibiotics target the large mtrRNA of the mitoribosome, we focused our analysis on mitochondrial translation. We found that the absence of non-essential translation factors Rrf1 or Mif3, which act at the recycling/initiation steps, also compensates for the respiratory deficiency of yeast bcs1 mutations. At compensating concentrations, both antibiotics, as well as the absence of Rrf1, cause an imbalanced synthesis of respiratory subunits which impairs the assembly of the respiratory complexes and especially that of complex IV. Finally, we show that pentamidine also decreases the assembly of complex I in nematode mitochondria. It is well known that complexes III and IV exist within the mitochondrial inner membrane as supramolecular complexes III 2 /IV in yeast or I/III 2 /IV in higher eukaryotes. Therefore, we propose that the changes in mitochondrial translation caused by the drugs or by the absence of translation factors, can compensate for bcs1 mutations by modifying the equilibrium between illegitimate, and thus inactive, and active supercomplexes. Copyright © 2017. Published by Elsevier B.V.

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine.

PubMed

Hartl, Dominik; Tirouvanziam, Rabindra; Laval, Julie; Greene, Catherine M; Habiel, David; Sharma, Lokesh; Yildirim, Ali Önder; Dela Cruz, Charles S; Hogaboam, Cory M

2018-02-13

The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract. © 2018 S. Karger AG, Basel.

[Autogenic training (AT)--respiratory feedback (RFB); similarities and limits in general practice oriented differential indications].

PubMed

Barolin, G S

1988-04-15

Autogenic Training (AT) is not merely a "relaxation exercise". We quote five dimensions of AT that should by clearly differentiated: 1) concentration, 2) relaxation, 3) vegetative switch toward the hypnoid state, 4) dynamising reprise exercise. 5) holistic inclusion in a complex psychotherapeutical concept. We consider the self induced hypnoid state plus dynamising reprise exercise as the main components for the beneficial effect of AT. The hynoid state has its neurophysiological definition as a third human state of consciousness. The reprise exercise is more than making it abolish, but has its own therapeutical values: dynamisation. Respiratory feedback (RBF - a special kind of biofeedback) has the factors relaxation and vegetative switch towards hypnoid in common with autogenic training. Where these components are specially requested, RFB proves valuable in therapy. In other indications however AT is of much better use. Namely: where the educational value of mutation, self-concentration and the therapeutic context is of predominant importance. AT as well as RFB may be considered "misused" in having them replace the therapeutical and understanding conversation between doctor and patients, in a mechanistic way. As a slogan it may be said: AT goes deeper, RFB goes quicker.

Marker-less respiratory motion modeling using the Microsoft Kinect for Windows

NASA Astrophysics Data System (ADS)

Tahavori, F.; Alnowami, M.; Wells, K.

2014-03-01

Patient respiratory motion is a major problem during external beam radiotherapy of the thoracic and abdominal regions due to the associated organ and target motion. In addition, such motion introduces uncertainty in both radiotherapy planning and delivery and may potentially vary between the planning and delivery sessions. The aim of this work is to examine subject-specific external respiratory motion and its associated drift from an assumed average cycle which is the basis for many respiratory motion compensated applications including radiotherapy treatment planning and delivery. External respiratory motion data were acquired from a group of 20 volunteers using a marker-less 3D depth camera, Kinect for Windows. The anterior surface encompassing thoracic and abdominal regions were subject to principal component analysis (PCA) to investigate dominant variations. The first principal component typically describes more than 70% of the motion data variance in the thoracic and abdominal surfaces. Across all of the subjects used in this study, 58% of subjects demonstrate largely abdominal breathing and 33% exhibited largely thoracic dominated breathing. In most cases there is observable drift in respiratory motion during the 300s capture period, which is visually demonstrated using Kernel Density Estimation. This study demonstrates that for this cohort of apparently healthy volunteers, there is significant respiratory motion drift in most cases, in terms of amplitude and relative displacement between the thoracic and abdominal respiratory components. This has implications for the development of effective motion compensation methodology.

Mitochondrial respiratory chain enzyme assay and DNA analysis in peripheral blood leukocytes for the etiological study of Chinese children with Leigh syndrome due to complex I deficiency.

PubMed

Ma, Yan Yan; Wu, Tong Fei; Liu, Yu Peng; Wang, Qiao; Li, Xi Yuan; Zhang, Yao; Song, Jin Qing; Wang, Yu Jie; Yang, Yan Ling

2013-02-01

Mitochondrial respiratory chain complex I enzyme deficiency is the most commonly seen mitochondrial respiratory chain disorder. Although screening and diagnostic methods are available overseas, clinically feasible diagnostic methods have not yet been established in China. In this study, four Chinese boys with Leigh syndrome due to complex I deficiency were diagnosed by mitochondrial respiratory chain enzyme assay and DNA analysis using peripheral blood leukocytes. Four patients were admitted at the age of 5-14 years because of unexplained progressive neuromuscular symptoms, including motor developmental delay or regression, weakness, and seizures. Their cranial magnetic resonance imaging revealed typical finding as Leigh syndrome. Peripheral leukocyte mitochondrial respiratory chain complex I activities were found decreased to 9.6-33.1 nmol/min/mg mitochondrial protein(control 44.0 ± 5.4 nmol/min/mg). The ratios of complex I to citrate synthase activity were also decreased (8.9-19.8% in patients vs. control 48 ± 11%). Three mtDNA mutations were identified from three out of four patients, supporting the diagnosis of complex I deficiency. Point mutations m.10191T>C in mitochondrial ND3 gene, m.13513G>A in ND5 gene and m.14,453G>A in ND6 gene were detected in three patients.

The respiratory-vocal system of songbirds: anatomy, physiology, and neural control.

PubMed

Schmidt, Marc F; Martin Wild, J

2014-01-01

This wide-ranging review presents an overview of the respiratory-vocal system in songbirds, which are the only other vertebrate group known to display a degree of respiratory control during song rivalling that of humans during speech; this despite the fact that the peripheral components of both the respiratory and vocal systems differ substantially in the two groups. We first provide a brief description of these peripheral components in songbirds (lungs, air sacs and respiratory muscles, vocal organ (syrinx), upper vocal tract) and then proceed to a review of the organization of central respiratory-related neurons in the spinal cord and brainstem, the latter having an organization fundamentally similar to that of the ventral respiratory group of mammals. The second half of the review describes the nature of the motor commands generated in a specialized "cortical" song control circuit and how these might engage brainstem respiratory networks to shape the temporal structure of song. We also discuss a bilaterally projecting "respiratory-thalamic" pathway that links the respiratory system to "cortical" song control nuclei. This necessary pathway for song originates in the brainstem's primary inspiratory center and is hypothesized to play a vital role in synchronizing song motor commands both within and across hemispheres. © 2014 Elsevier B.V. All rights reserved.

The respiratory-vocal system of songbirds: Anatomy, physiology, and neural control

PubMed Central

Schmidt, Marc F.; Wild, J. Martin

2015-01-01

This wide-ranging review presents an overview of the respiratory-vocal system in songbirds, which are the only other vertebrate group known to display a degree of respiratory control during song rivalling that of humans during speech; this despite the fact that the peripheral components of both the respiratory and vocal systems differ substantially in the two groups. We first provide a brief description of these peripheral components in songbirds (lungs, air sacs and respiratory muscles, vocal organ (syrinx), upper vocal tract) and then proceed to a review of the organization of central respiratory-related neurons in the spinal cord and brainstem, the latter having an organization fundamentally similar to that of the ventral respiratory group of mammals. The second half of the review describes the nature of the motor commands generated in a specialized “cortical” song control circuit and how these might engage brainstem respiratory networks to shape the temporal structure of song. We also discuss a bilaterally projecting “respiratory-thalamic” pathway that links the respiratory system to “cortical” song control nuclei. This necessary pathway for song originates in the brainstem’s primary inspiratory center and is hypothesized to play a vital role in synchronizing song motor commands both within and across hemispheres. PMID:25194204

The clinical maze of mitochondrial neurology

PubMed Central

DiMauro, Salvatore; Schon, Eric A.; Carelli, Valerio; Hirano, Michio

2014-01-01

Mitochondrial diseases involve the respiratory chain, which is under the dual control of nuclear and mitochondrial DNA (mtDNA). The complexity of mitochondrial genetics provides one explanation for the clinical heterogeneity of mitochondrial diseases, but our understanding of disease pathogenesis remains limited. Classification of Mendelian mitochondrial encephalomyopathies has been laborious, but whole-exome sequencing studies have revealed unexpected molecular aetiologies for both typical and atypical mitochondrial disease phenotypes. Mendelian mitochondrial defects can affect five components of mitochondrial biology: subunits of respiratory chain complexes (direct hits); mitochondrial assembly proteins; mtDNA translation; phospholipid composition of the inner mitochondrial membrane; or mitochondrial dynamics. A sixth category—defects of mtDNA maintenance—combines features of Mendelian and mitochondrial genetics. Genetic defects in mitochondrial dynamics are especially important in neurology as they cause optic atrophy, hereditary spastic paraplegia, and Charcot–Marie–Tooth disease. Therapy is inadequate and mostly palliative, but promising new avenues are being identified. Here, we review current knowledge on the genetics and pathogenesis of the six categories of mitochondrial disorders outlined above, focusing on their salient clinical manifestations and highlighting novel clinical entities. An outline of diagnostic clues for the various forms of mitochondrial disease, as well as potential therapeutic strategies, is also discussed. PMID:23835535

UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction.

PubMed

Kazak, Lawrence; Chouchani, Edward T; Stavrovskaya, Irina G; Lu, Gina Z; Jedrychowski, Mark P; Egan, Daniel F; Kumari, Manju; Kong, Xingxing; Erickson, Brian K; Szpyt, John; Rosen, Evan D; Murphy, Michael P; Kristal, Bruce S; Gygi, Steven P; Spiegelman, Bruce M

2017-07-25

Brown adipose tissue (BAT) mitochondria exhibit high oxidative capacity and abundant expression of both electron transport chain components and uncoupling protein 1 (UCP1). UCP1 dissipates the mitochondrial proton motive force (Δp) generated by the respiratory chain and increases thermogenesis. Here we find that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT. Moreover, global proteomic analysis reveals that this cascade induced by UCP1 deletion is associated with a dramatic reduction in electron transport chain abundance. UCP1-deficient BAT mitochondria exhibit reduced mitochondrial calcium buffering capacity and are highly sensitive to mitochondrial permeability transition induced by reactive oxygen species (ROS) and calcium overload. This dysfunction depends on ROS production by reverse electron transport through mitochondrial complex I, and can be rescued by inhibition of electron transfer through complex I or pharmacologic depletion of ROS levels. Our findings indicate that the interscapular BAT of Ucp1 knockout mice exhibits mitochondrial disruptions that extend well beyond the deletion of UCP1 itself. This finding should be carefully considered when using this mouse model to examine the role of UCP1 in physiology.

Evaluation of respiratory muscles activity by means of cross mutual information function at different levels of ventilatory effort.

PubMed

Alonso, Joan Francesc; Mañanas, Miguel A; Hoyer, Dirk; Topor, Zbigniew L; Bruce, Eugene N

2007-09-01

Analysis of respiratory muscles activity is an effective technique for the study of pulmonary diseases such as obstructive sleep apnea syndrome (OSAS). Respiratory diseases, especially those associated with changes in the mechanical properties of the respiratory apparatus, are often associated with disruptions of the normally highly coordinated contractions of respiratory muscles. Due to the complexity of the respiratory control, the assessment of OSAS related dysfunctions by linear methods are not sufficient. Therefore, the objective of this study was the detection of diagnostically relevant nonlinear complex respiratory mechanisms. Two aims of this work were: (1) to assess coordination of respiratory muscles contractions through evaluation of interactions between respiratory signals and myographic signals through nonlinear analysis by means of cross mutual information function (CMIF); (2) to differentiate between functioning of respiratory muscles in patients with OSAS and in normal subjects. Electromyographic (EMG) and mechanomyographic (MMG) signals were recorded from three respiratory muscles: genioglossus, sternomastoid and diaphragm. Inspiratory pressure and flow were also acquired. All signals were measured in eight patients with OSAS and eight healthy subjects during an increased respiratory effort while awake. Several variables were defined and calculated from CMIF in order to describe correlation between signals. The results indicate different nonlinear couplings of respiratory muscles in both populations. This effect is progressively more evident at higher levels of respiratory effort.

A closed-loop model of the respiratory system: focus on hypercapnia and active expiration.

PubMed

Molkov, Yaroslav I; Shevtsova, Natalia A; Park, Choongseok; Ben-Tal, Alona; Smith, Jeffrey C; Rubin, Jonathan E; Rybak, Ilya A

2014-01-01

Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. During quiet breathing, pumping air from the lungs is mostly performed by contraction of the diaphragm during inspiration, and muscle contraction during expiration does not play a significant role in ventilation. In contrast, during intense exercise or severe hypercapnia forced or active expiration occurs in which the abdominal "expiratory" muscles become actively involved in breathing. The mechanisms of this transition remain unknown. To study these mechanisms, we developed a computational model of the closed-loop respiratory system that describes the brainstem respiratory network controlling the pulmonary subsystem representing lung biomechanics and gas (O2 and CO2) exchange and transport. The lung subsystem provides two types of feedback to the neural subsystem: a mechanical one from pulmonary stretch receptors and a chemical one from central chemoreceptors. The neural component of the model simulates the respiratory network that includes several interacting respiratory neuron types within the Bötzinger and pre-Bötzinger complexes, as well as the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) representing the central chemoreception module targeted by chemical feedback. The RTN/pFRG compartment contains an independent neural generator that is activated at an increased CO2 level and controls the abdominal motor output. The lung volume is controlled by two pumps, a major one driven by the diaphragm and an additional one activated by abdominal muscles and involved in active expiration. The model represents the first attempt to model the transition from quiet breathing to breathing with active expiration. The model suggests that the closed-loop respiratory control system switches to active expiration via a quantal acceleration of expiratory activity, when increases in breathing rate and phrenic amplitude no longer provide sufficient ventilation. The model can be used for simulation of closed-loop control of breathing under different conditions including respiratory disorders.

Association between respiratory impedance measured by forced oscillation technique and exacerbations in patients with COPD.

PubMed

Yamagami, Hitomi; Tanaka, Akihiko; Kishino, Yasunari; Mikuni, Hatsuko; Kawahara, Tomoko; Ohta, Shin; Yamamoto, Mayumi; Suzuki, Shintaro; Ohnishi, Tsukasa; Sagara, Hironori

2018-01-01

It is well known that increased airflow limitation as measured by spirometry is associated with the risk of exacerbation in patients with COPD. The forced oscillation technique (FOT) is a noninvasive method used to assess respiratory impedance (resistance and reactance) with minimal patient cooperation required. The clinical utility of the FOT in assessing the risk of exacerbations of COPD is yet to be determined. We examined the relationship between respiratory impedance as measured by FOT and exacerbations in patients with COPD. Among 310 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stages I-IV) who presented at the outpatient clinic of the Showa University Hospital from September 2014 through January 2015, 119 were collected and assigned into 2 groups according to their history of exacerbation: exacerbators and nonexacerbators. Respiratory resistance components and respiratory reactance components, as measured by FOT, were compared between the two groups. Exacerbators were significantly older and had a higher white blood cell count than nonexacerbators. Resistance at 20 Hz, reactance at 5 Hz (X5), resonant frequency (Fres), and area of low reactance (ALX) differed significantly between the two groups. In addition, among patients with stage II COPD, there were significant differences in X5, Fres, and ALX between the two groups despite no significant differences in respiratory function as assessed by spirometry. Finally, receiver operating characteristic curve analysis revealed that the reactance components rather than the resistance components were associated with the risk of exacerbation. There were significant differences in respiratory impedance between exacerbators and nonexacerbators in patients with moderate COPD. FOT is a promising tool for assessing future exacerbations in patients with COPD.

MOUSE SKIN TUMORS AND HUMAN LUNG CANCER: RELATIONSHIPS WITH COMPLEX ENVIRONMENTAL EMISSIONS

EPA Science Inventory

Historically, mouse skin tumorigenesis has been used to evaluate the tumorigenic effects of complex mixtures including human respiratory carcinogens. his study examines the quantitative relationships between tumor induction in SENCAR mouse skin and the induction of respiratory ca...

The Assembly Pathway of Mitochondrial Respiratory Chain Complex I.

PubMed

Guerrero-Castillo, Sergio; Baertling, Fabian; Kownatzki, Daniel; Wessels, Hans J; Arnold, Susanne; Brandt, Ulrich; Nijtmans, Leo

2017-01-10

Mitochondrial complex I is the largest integral membrane enzyme of the respiratory chain and consists of 44 different subunits encoded in the mitochondrial and nuclear genome. Its biosynthesis is a highly complicated and multifaceted process involving at least 14 additional assembly factors. How these subunits assemble into a functional complex I and where the assembly factors come into play is largely unknown. Here, we applied a dynamic complexome profiling approach to elucidate the assembly of human mitochondrial complex I and its further incorporation into respiratory chain supercomplexes. We delineate the stepwise incorporation of all but one subunit into a series of distinct assembly intermediates and their association with known and putative assembly factors, which had not been implicated in this process before. The resulting detailed and comprehensive model of complex I assembly is fully consistent with recent structural data and the remarkable modular architecture of this multiprotein complex. Copyright © 2017 Elsevier Inc. All rights reserved.

Critical-thinking ability in respiratory care students and its correlation with age, educational background, and performance on national board examinations.

PubMed

Wettstein, Richard B; Wilkins, Robert L; Gardner, Donna D; Restrepo, Ruben D

2011-03-01

Critical thinking is an important characteristic to develop in respiratory care students. We used the short-form Watson-Glaser Critical Thinking Appraisal instrument to measure critical-thinking ability in 55 senior respiratory care students in a baccalaureate respiratory care program. We calculated the Pearson correlation coefficient to assess the relationships between critical-thinking score, age, and student performance on the clinical-simulation component of the national respiratory care boards examination. We used chi-square analysis to assess the association between critical-thinking score and educational background. There was no significant relationship between critical-thinking score and age, or between critical-thinking score and student performance on the clinical-simulation component. There was a significant (P = .04) positive association between a strong science-course background and critical-thinking score, which might be useful in predicting a student's ability to perform in areas where critical thinking is of paramount importance, such as clinical competencies, and to guide candidate-selection for respiratory care programs.

Sulphate respiration from hydrogen in Desulfovibrio bacteria: a structural biology overview.

PubMed

Matias, Pedro M; Pereira, Inês A C; Soares, Cláudio M; Carrondo, Maria Arménia

2005-11-01

Sulphate-reducing organisms are widespread in anaerobic enviroments, including the gastrointestinal tract of man and other animals. The study of these bacteria has attracted much attention over the years, due also to the fact that they can have important implications in industry (in biocorrosion and souring of oil and gas deposits), health (in inflamatory bowel diseases) and the environment (bioremediation). The characterization of the various components of the electron transport chain associated with the hydrogen metabolism in Desulfovibrio has generated a large and comprehensive list of studies. This review summarizes the more relevant aspects of the current information available on the structural data of various molecules associated with hydrogen metabolism, namely hydrogenases and cytochromes. The transmembrane redox complexes known to date are also described and discussed. Redox-Bohr and cooperativity effects, observed in a few cytochromes, and believed to be important for their functional role, are discussed. Kinetic studies performed with these redox proteins, showing clues to their functional inter-relationship, are also addressed. These provide the groundwork for the application of a variety of molecular modelling approaches to understanding electron transfer and protein interactions among redox partners, leading to the characterization of several transient periplasmic complexes. In contrast to the detailed understanding of the periplasmic hydrogen oxidation process, very little is known about the cytoplasmic side of the respiratory electron transfer chain, in terms of molecular components (with exception of the terminal reductases), their structure and the protein-protein interactions involved in sulphate reduction. Therefore, a thorough understanding of the sulphate respiratory chain in Desulfovibrio remains a challenging task.

Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease

PubMed Central

Kong, Su-Kang; Soo Kim, Byung; Gi Uhm, Tae; Soo Chang, Hun; Sook Park, Jong; Woo Park, Sung; Park, Choon-Sik; Chung, Il Yup

2016-01-01

Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin. Aspirin induced IL-4 expression and activated the IL-4 promoter in a report assay. The capacity of aspirin to induce IL-4 expression correlated with its activity to activate mitogen-activated protein kinases, to form DNA–protein complexes on P elements in the IL-4 promoter and to synthesize nuclear factor of activated T cells, critical transcription factors for IL-4 transcription. Of clinical importance, aspirin upregulated IL-4 production twice as much in PBMCs from patients with AERD compared with PBMCs from patients with ATA. Our results suggest that IL-4 is an inflammatory component mediating intolerance reactions to aspirin, and thus is crucial for AERD pathogenesis. PMID:27534531

Control of electron transport routes through redox-regulated redistribution of respiratory complexes

PubMed Central

Liu, Lu-Ning; Bryan, Samantha J.; Huang, Fang; Yu, Jianfeng; Nixon, Peter J.; Rich, Peter R.; Mullineaux, Conrad W.

2012-01-01

In cyanobacteria, respiratory electron transport takes place in close proximity to photosynthetic electron transport, because the complexes required for both processes are located within the thylakoid membranes. The balance of electron transport routes is crucial for cell physiology, yet the factors that control the predominance of particular pathways are poorly understood. Here we use a combination of tagging with green fluorescent protein and confocal fluorescence microscopy in live cells of the cyanobacterium Synechococcus elongatus PCC 7942 to investigate the distribution on submicron scales of two key respiratory electron donors, type-I NAD(P)H dehydrogenase (NDH-1) and succinate dehydrogenase (SDH). When cells are grown under low light, both complexes are concentrated in discrete patches in the thylakoid membranes, about 100–300 nm in diameter and containing tens to hundreds of complexes. Exposure to moderate light leads to redistribution of both NDH-1 and SDH such that they become evenly distributed within the thylakoid membranes. The effects of electron transport inhibitors indicate that redistribution of respiratory complexes is triggered by changes in the redox state of an electron carrier close to plastoquinone. Redistribution does not depend on de novo protein synthesis, and it is accompanied by a major increase in the probability that respiratory electrons are transferred to photosystem I rather than to a terminal oxidase. These results indicate that the distribution of complexes on the scale of 100–300 nm controls the partitioning of reducing power and that redistribution of electron transport complexes on these scales is a physiological mechanism to regulate the pathways of electron flow. PMID:22733774

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone.

PubMed

Wijnhoven, Hanneke J H; Ennen, Leo; Rodenburg, Richard J T; Dekhuijzen, P N Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model.

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone

PubMed Central

Wijnhoven, Hanneke JH; Ennen, Leo; Rodenburg, Richard JT; Dekhuijzen, PN Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model. PMID:18046906

[Impacts of airborne particulate matter and its components on respiratory system health].

PubMed

Cao, L M; Zhou, Y; Zhang, Z; Sun, W W; Mu, G; Chen, W H

2016-12-06

Nowadays, particulate air pollution has been a global environmental problem. Numerous studies has shown that long-term exposure to high level of airborne particulate matter (PM) can damage human health. Respiratory system, as a direct portal to contact with particulate matter, can be more susceptible to airborne particulates. Summarizing latest five-year epidemiological research, the present review is focused on the effects of PM on respiratory system health in different age groups. In detail, we investigated the harmful effect of PM, or its components on three common respiratory diseases, including lung function decline, chronic obstructive pulmonary disease (COPD) and asthma. The result showed that, to a certain degree, PM could induce the decline of lung function, the development and the exacerbation of COPD and asthma by oxidative stress and inflammatory reaction. And it may prompt that exposure to PM can be an improtant risk factor for the respiratory system health.

[Lysozyme in the treatment of juvenile laryngeal papillomatosis. A new concept in its etiopathogenesis].

PubMed

Altamar-Ríos, J

1990-01-01

The A. inform about the results achieved with lysozyme chlorhydrate in the treatment of 15 patients with juvenile laryngeal papillomatosis. The lysozyme is an electropositive enzyme which synthesis is related to the degree of proteins and vitamin B complex ingestion. Lysozyme is a component of the immunitary inespecific system, serving to prevent against HPV-DNA at the level of the secretory film of the mucociliary apparatus of the respiratory mucous membrane. Furthermore, lysozyme hydrolyzes the mucopolysaccharide of the connective tissue and inhibits the virus-DNA replication. 100-300 mgr daily during 30-60 days simultaneously with hyperproteic diet and vitamin B complex (after correction of the nutrimental deficiencies) brought about the evanishment of papillomatosis. The A. suggest that the predisposition to infection by virus DNA is primarily of immunitary origin, because of lysozyme deficiency, and secondary due to a low intake of proteins and vitamin B complex.

Respiratory and metabolic acidosis differentially affect the respiratory neuronal network in the ventral medulla of neonatal rats.

PubMed

Okada, Yasumasa; Masumiya, Haruko; Tamura, Yoshiyasu; Oku, Yoshitaka

2007-11-01

Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.

SU-E-J-261: Statistical Analysis and Chaotic Dynamics of Respiratory Signal of Patients in BodyFix

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

Michalski, D; Huq, M; Bednarz, G

Purpose: To quantify respiratory signal of patients in BodyFix undergoing 4DCT scan with and without immobilization cover. Methods: 20 pairs of respiratory tracks recorded with RPM system during 4DCT scan were analyzed. Descriptive statistic was applied to selected parameters of exhale-inhale decomposition. Standardized signals were used with the delay method to build orbits in embedded space. Nonlinear behavior was tested with surrogate data. Sample entropy SE, Lempel-Ziv complexity LZC and the largest Lyapunov exponents LLE were compared. Results: Statistical tests show difference between scans for inspiration time and its variability, which is bigger for scans without cover. The same ismore » for variability of the end of exhalation and inhalation. Other parameters fail to show the difference. For both scans respiratory signals show determinism and nonlinear stationarity. Statistical test on surrogate data reveals their nonlinearity. LLEs show signals chaotic nature and its correlation with breathing period and its embedding delay time. SE, LZC and LLE measure respiratory signal complexity. Nonlinear characteristics do not differ between scans. Conclusion: Contrary to expectation cover applied to patients in BodyFix appears to have limited effect on signal parameters. Analysis based on trajectories of delay vectors shows respiratory system nonlinear character and its sensitive dependence on initial conditions. Reproducibility of respiratory signal can be evaluated with measures of signal complexity and its predictability window. Longer respiratory period is conducive for signal reproducibility as shown by these gauges. Statistical independence of the exhale and inhale times is also supported by the magnitude of LLE. The nonlinear parameters seem more appropriate to gauge respiratory signal complexity since its deterministic chaotic nature. It contrasts with measures based on harmonic analysis that are blind for nonlinear features. Dynamics of breathing, so crucial for 4D-based clinical technologies, can be better controlled if nonlinear-based methodology, which reflects respiration characteristic, is applied. Funding provided by Varian Medical Systems via Investigator Initiated Research Project.« less

Respiratory chain complex III deficiency in patients with tRNA-leu mutation.

PubMed

Jiang, J; Wang, X L; Ma, Y Y

2015-12-29

The aim of this study was to investigate the clinical and genetic profiles of mitochondrial disease resulting from deficiencies in the respiratory chain complex III. Three patients, aged between 8 months and 12 years, were recruited for this study. The activities of mitochondrial respiratory chain complexes in the peripheral leucocytes were spectrophotometrically measured. The entire mitochondrial DNA (mtDNA) sequence was analyzed. Samples obtained from the three patients and their families were subjected to restriction fragment length polymorphism and gene sequencing analyses. mtDNA copy numbers of all patients and their mothers were analyzed. The patients displayed nervous system impairment, including motor and mental developmental delay, hypotonia, and motor regression. Two patients also suffered from Leigh syndrome. Assay of the mitochondrial respiratory chain enzymes revealed an isolated complex III deficiency in the three patients. The m.3243 A>G mutation was detected in all patients and their mothers. The mutation loads were 48.3, 57.2, and 45.5% in the patients, and 20.5, 16.4, and 23.6% in their respective mothers. The leukocyte mtDNA copy numbers of the patients and their mothers were within the control range. The clinical manifestation and genetics were observed to be very heterogeneous. Patient carrying an m.3243 A>G mutation may biochemically display a deficiency in the mitochondrial respiratory chain complex III.

Phenyl-alpha-tert-butyl nitrone reverses mitochondrial decay in acute Chagas' disease.

PubMed

Wen, Jian-Jun; Bhatia, Vandanajay; Popov, Vsevolod L; Garg, Nisha Jain

2006-12-01

In this study, we investigated the mechanism(s) of mitochondrial functional decline in acute Chagas' disease. Our data show a substantial decline in respiratory complex activities (39 to 58%) and ATP (38%) content in Trypanosoma cruzi-infected murine hearts compared with normal controls. These metabolic alterations were associated with an approximately fivefold increase in mitochondrial reactive oxygen species production rate, substantial oxidative insult of mitochondrial membranes and respiratory complex subunits, and >60% inhibition of mtDNA-encoded transcripts for respiratory complex subunits in infected myocardium. The antioxidant phenyl-alpha-tert-butyl nitrone (PBN) arrested the oxidative damage-mediated loss in mitochondrial membrane integrity, preserved redox potential-coupled mitochondrial gene expression, and improved respiratory complex activities (47 to 95% increase) and cardiac ATP level (>or=40% increase) in infected myocardium. Importantly, PBN resulted twofold decline in mitochondrial reactive oxygen species production rate in infected myocardium. Taken together, our data demonstrate the pathological significance of oxidative stress in metabolic decay and energy homeostasis in acute chagasic myocarditis and further suggest that oxidative injuries affecting mitochondrial integrity-dependent expression and activity of the respiratory complexes initiate a feedback cycle of electron transport chain inefficiency, increased reactive oxygen species production, and energy homeostasis in acute chagasic hearts. PBN and other mitochondria-targeted antioxidants may be useful in altering mitochondrial decay and oxidative pathology in Chagas' disease.

[The clinical economic analysis of application of immune correcting preparations to prevent respiratory infections and their complications in frequently ill children of early school age].

PubMed

Maiorov, R V; Derbenov, D P

2014-01-01

The article presents the results of clinical economic analysis of effect of different immune correcting preparations on rate of respiratory infections in 548 frequently ill children of early school age. It is established that preventive immune correction with lysates of bacteria or glucosaminyl muramyl dipeptide in aggregate with vitamin mineral complex results in statistically significant decreasing of rate of respiratory infections and dramatic decreasing of direct and indirect costs of treatment of infectious diseases of respiratory ways. The preventive application of juice of cone-flower herb or interferon in aggregate with vitamnin mineral complex statistically significantly decreases rate of respiratory infections and negligibly decreases direct and indirect costs of their treatment.

Complexity of intracranial pressure correlates with outcome after traumatic brain injury

PubMed Central

Lu, Cheng-Wei; Czosnyka, Marek; Shieh, Jiann-Shing; Smielewska, Anna; Pickard, John D.

2012-01-01

This study applied multiscale entropy analysis to investigate the correlation between the complexity of intracranial pressure waveform and outcome after traumatic brain injury. Intracranial pressure and arterial blood pressure waveforms were low-pass filtered to remove the respiratory and pulse components and then processed using a multiscale entropy algorithm to produce a complexity index. We identified significant differences across groups classified by the Glasgow Outcome Scale in intracranial pressure, pressure-reactivity index and complexity index of intracranial pressure (P < 0.0001; P = 0.001; P < 0.0001, respectively). Outcome was dichotomized as survival/death and also as favourable/unfavourable. The complexity index of intracranial pressure achieved the strongest statistical significance (F = 28.7; P < 0.0001 and F = 17.21; P < 0.0001, respectively) and was identified as a significant independent predictor of mortality and favourable outcome in a multivariable logistic regression model (P < 0.0001). The results of this study suggest that complexity of intracranial pressure assessed by multiscale entropy was significantly associated with outcome in patients with brain injury. PMID:22734128

A Characterization of the Oral Microbiome in Allogeneic Stem Cell Transplant Patients

PubMed Central

Ames, Nancy J.; Sulima, Pawel; Ngo, Thoi; Barb, Jennifer; Munson, Peter J.; Paster, Bruce J.; Hart, Thomas C.

2012-01-01

Background The mouth is a complex biological structure inhabited by diverse bacterial communities. The purpose of this study is to describe the effects of allogeneic stem cell transplantation on the oral microbiota and to examine differences among those patients who acquired respiratory complications after transplantation. Methodology/Principal Findings All patients were consented at the National Institutes of Health, Clinical Center. Bacterial DNA was analyzed from patients' oral specimens using the Human Oral Microbe Identification Microarray. The specimens were collected from four oral sites in 45 allogeneic transplantation patients. Specimens were collected at baseline prior to transplantation, after transplantation at the nadir of the neutrophil count and after myeloid engraftment. If respiratory signs and symptoms developed, additional specimens were obtained. Patients were followed for 100 days post transplantation. Eleven patients' specimens were subjected to further statistical analysis. Many common bacterial genera, such as Streptococcus, Veillonella, Gemella, Granulicatella and Camplyobacter were identified as being present before and after transplantation. Five of 11 patients developed respiratory complications following transplantation and there was preliminary evidence that the oral microbiome changed in their oral specimens. Cluster analysis and principal component analysis revealed this change in the oral microbiota. Conclusions/Significance After allogeneic transplantation, the oral bacterial community's response to a new immune system was not apparent and many of the most common core oral taxa remained unaffected. However, the oral microbiome was affected in patients who developed respiratory signs and symptoms after transplantation. The association related to the change in the oral microbiota and respiratory complications after transplantation will be validated by future studies using high throughput molecular methods. PMID:23144704

Bovine coronavirus antibody titers at weaning negatively correlate with incidence of bovine respiratory disease in the feed yard

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a multifactorial disease caused by complex interactions among viral and bacterial pathogens, stressful management practices and host genetic variability. Although vaccines and antibiotic treatments are readily available to prevent and treat infection caus...

Closed genomes of seven histophilus somni isolates from beef calves with bovine respiratory disease complex

USDA-ARS?s Scientific Manuscript database

Histophilus somni is a fastidious gram-negative opportunistic pathogenic Pasteurellacea that affects multiple organ systems and is one of the principle bacterial species contributing to bovine respiratory disease complex (BRDC) in feed yard cattle. Here we present seven closed genomes isolated from...

Closed genomes and phenotypes of seven Histophilus somni isolates from beef calves with bovine respiratory disease complex

USDA-ARS?s Scientific Manuscript database

Background: Histophilus somni is a fastidious gram-negative opportunistic pathogenic Pasteurellacea that affects multiple organ systems and is one of three principle bacterial species contributing to bovine respiratory disease complex (BRDC) in North American feed yard cattle. BRDC outbreaks accoun...

Small non-coding RNAs (sncRNA) regulate gene silencing and modify homeostatic status in animals faced with porcine reproductive and respiratory syndrome virus (PRRSV)

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration.

PubMed

Fišar, Z; Hroudová, J; Singh, N; Kopřivová, A; Macečková, D

2016-01-01

Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 μM for Complex I-linked respiration, IC50 = 31.3 μM for Complex II-linked respiration, and IC50 = 42.9 μM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 μM for Complex I-linked respiration, IC50 = 564 μM for Complex II-linked respiration, and IC50 = 1454 μM for Complex IV-linked respiration). Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

The mitochondrial disulfide relay system protein GFER is mutated in autosomal-recessive myopathy with cataract and combined respiratory-chain deficiency.

PubMed

Di Fonzo, Alessio; Ronchi, Dario; Lodi, Tiziana; Fassone, Elisa; Tigano, Marco; Lamperti, Costanza; Corti, Stefania; Bordoni, Andreina; Fortunato, Francesco; Nizzardo, Monica; Napoli, Laura; Donadoni, Chiara; Salani, Sabrina; Saladino, Francesca; Moggio, Maurizio; Bresolin, Nereo; Ferrero, Iliana; Comi, Giacomo P

2009-05-01

A disulfide relay system (DRS) was recently identified in the yeast mitochondrial intermembrane space (IMS) that consists of two essential components: the sulfhydryl oxidase Erv1 and the redox-regulated import receptor Mia40. The DRS drives the import of cysteine-rich proteins into the IMS via an oxidative folding mechanism. Erv1p is reoxidized within this system, transferring its electrons to molecular oxygen through interactions with cytochrome c and cytochrome c oxidase (COX), thereby linking the DRS to the respiratory chain. The role of the human Erv1 ortholog, GFER, in the DRS has been poorly explored. Using homozygosity mapping, we discovered that a mutation in the GFER gene causes an infantile mitochondrial disorder. Three children born to healthy consanguineous parents presented with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. The consequences of the mutation at the level of the patient's muscle tissue and fibroblasts were 1) a reduction in complex I, II, and IV activity; 2) a lower cysteine-rich protein content; 3) abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and 4) accelerated time-dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces cerevisiae erv1(R182H) mutant strain reproduced the complex IV activity defect and exhibited genetic instability of the mtDNA and mitochondrial morphological defects. These findings shed light on the mechanisms of mitochondrial biogenesis, establish the role of GFER in the human DRS, and promote an understanding of the pathogenesis of a new mitochondrial disease.

The patient with a complex chronic respiratory disease: a specialist of his own life?

PubMed

Houben-Wilke, Sarah; Augustin, Ingrid Ml; Wouters, Birgit Bref; Stevens, Rosita Ah; Janssen, Daisy Ja; Spruit, Martijn A; Vanfleteren, Lowie Egw; Franssen, Frits Me; Wouters, Emiel Fm

2017-12-01

The independent and central role of the patient with a complex chronic respiratory disease in targeted, personalized disease management strategies is becoming increasingly important. Patients are the ones living with the disease and are finally responsible for their lives underlining their role as essential members of the interdisciplinary treatment team. Areas covered: The present paper narratively reviews existing research and discusses the special, as well as specialized, role of the patient with a complex chronic respiratory disease in the healthcare system and highlights fundamental elements of the (future) relationship between patient and healthcare professionals. Expert commentary: Since the chronic respiratory disease at hand is part of the patient's entire life, we need holistic, personalized approaches optimizing patients' quality of life by not only treating the disease but considering the patients' whole environment and where healthcare professionals and patients are co-creating value care.

Respiratory protective device design using control system techniques

NASA Technical Reports Server (NTRS)

Burgess, W. A.; Yankovich, D.

1972-01-01

The feasibility of a control system analysis approach to provide a design base for respiratory protective devices is considered. A system design approach requires that all functions and components of the system be mathematically identified in a model of the RPD. The mathematical notations describe the operation of the components as closely as possible. The individual component mathematical descriptions are then combined to describe the complete RPD. Finally, analysis of the mathematical notation by control system theory is used to derive compensating component values that force the system to operate in a stable and predictable manner.

The effect of acute exposure to hyperbaric oxygen on respiratory system mechanics in the rat.

PubMed

Rubini, Alessandro; Porzionato, Andrea; Zara, Susi; Cataldi, Amelia; Garetto, Giacomo; Bosco, Gerardo

2013-10-01

This study was designed to investigate the possible effects of acute hyperbaric hyperoxia on respiratory mechanics of anaesthetised, positive-pressure ventilated rats. We measured respiratory mechanics by the end-inflation occlusion method in nine rats previously acutely exposed to hyperbaric hyperoxia in a standard fashion. The method allows the measurements of respiratory system elastance and of both the "ohmic" and of the viscoelastic components of airway resistance, which respectively depend on the newtonian pressure dissipation due to the ohmic airway resistance to air flow, and on the viscoelastic pressure dissipation caused by respiratory system tissues stress-relaxation. The activities of inducible and endothelial NO-synthase in the lung's tissues (iNOS and eNOS respectively) also were investigated. Data were compared with those obtained in control animals. We found that the exposure to hyperbaric hyperoxia increased respiratory system elastance and both the "ohmic" and viscoelastic components of inspiratory resistances. These changes were accompanied by increased iNOS but not eNOS activities. Hyperbaric hyperoxia was shown to acutely induce detrimental effects on respiratory mechanics. A possible causative role was suggested for increased nitrogen reactive species production because of increased iNOS activity.

Mitoregulin: A lncRNA-Encoded Microprotein that Supports Mitochondrial Supercomplexes and Respiratory Efficiency.

PubMed

Stein, Colleen S; Jadiya, Pooja; Zhang, Xiaoming; McLendon, Jared M; Abouassaly, Gabrielle M; Witmer, Nathan H; Anderson, Ethan J; Elrod, John W; Boudreau, Ryan L

2018-06-26

Mitochondria are composed of many small proteins that control protein synthesis, complex assembly, metabolism, and ion and reactive oxygen species (ROS) handling. We show that a skeletal muscle- and heart-enriched long non-coding RNA, LINC00116, encodes a highly conserved 56-amino-acid microprotein that we named mitoregulin (Mtln). Mtln localizes to the inner mitochondrial membrane, where it binds cardiolipin and influences protein complex assembly. In cultured cells, Mtln overexpression increases mitochondrial membrane potential, respiration rates, and Ca 2+ retention capacity while decreasing mitochondrial ROS and matrix-free Ca 2+ . Mtln-knockout mice display perturbations in mitochondrial respiratory (super)complex formation and activity, fatty acid oxidation, tricarboxylic acid (TCA) cycle enzymes, and Ca 2+ retention capacity. Blue-native gel electrophoresis revealed that Mtln co-migrates alongside several complexes, including the complex I assembly module, complex V, and supercomplexes. Under denaturing conditions, Mtln remains in high-molecular-weight complexes, supporting its role as a sticky molecular tether that enhances respiratory efficiency by bolstering protein complex assembly and/or stability. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Epidemiologic evidence for asthma and exposure to air toxics: linkages between occupational, indoor, and community air pollution research.

PubMed Central

Delfino, Ralph J

2002-01-01

Outdoor ambient air pollutant exposures in communities are relevant to the acute exacerbation and possibly the onset of asthma. However, the complexity of pollutant mixtures and etiologic heterogeneity of asthma has made it difficult to identify causal components in those mixtures. Occupational exposures associated with asthma may yield clues to causal components in ambient air pollution because such exposures are often identifiable as single-chemical agents (e.g., metal compounds). However, translating occupational to community exposure-response relationships is limited. Of the air toxics found to cause occupational asthma, only formaldehyde has been frequently investigated in epidemiologic studies of allergic respiratory responses to indoor air, where general consistency can be shown despite lower ambient exposures. The specific volatile organic compounds (VOCs) identified in association with occupational asthma are generally not the same as those in studies showing respiratory effects of VOC mixtures on nonoccupational adult and pediatric asthma. In addition, experimental evidence indicates that airborne polycyclic aromatic hydrocarbon (PAH) exposures linked to diesel exhaust particles (DEPs) have proinflammatory effects on airways, but there is insufficient supporting evidence from the occupational literature of effects of DEPs on asthma or lung function. In contrast, nonoccupational epidemiologic studies have frequently shown associations between allergic responses or asthma with exposures to ambient air pollutant mixtures with PAH components, including black smoke, high home or school traffic density (particularly truck traffic), and environmental tobacco smoke. Other particle-phase and gaseous co-pollutants are likely causal in these associations as well. Epidemiologic research on the relationship of both asthma onset and exacerbation to air pollution is needed to disentangle effects of air toxics from monitored criteria air pollutants such as particle mass. Community studies should focus on air toxics expected to have adverse respiratory effects based on biological mechanisms, particularly irritant and immunological pathways to asthma onset and exacerbation. PMID:12194890

Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

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

Simarro, Maria; Gimenez-Cassina, Alfredo; Kedersha, Nancy

2010-10-22

Research highlights: {yields} Five members of the FAST kinase domain-containing proteins are localized to mitochondria in mammalian cells. {yields} The FASTKD3 interactome includes proteins involved in various aspects of mitochondrial metabolism. {yields} Targeted knockdown of FASTKD3 significantly reduces basal and maximal mitochondrial oxygen consumption. -- Abstract: Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated withmore » reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.« less

Respiratory chain inhibition: one more feature to propose MPTP intoxication as a Leigh syndrome model.

PubMed

Da Costa, Barbara; Dumon, Elodie; Le Moigno, Laurence; Bodard, Sylvie; Castelnau, Pierre; Letellier, Thierry; Rocher, Christophe

2016-10-01

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice have been widely used to model the loss of dopaminergic neurons. As this treatment leads to basal ganglia degeneration, it was proposed that MPTP mice could be used as a model of Leigh syndrome. However, this mitochondrial pathology is biochemically characterized by a respiratory chain dysfunction. To determine if MPTP can affect in vivo mitochondria function, we measured the activities of mitochondrial respiratory chain complexes in several tissues. Our results show that MPTP affects mainly mitochondrial respiratory chain complex IV, as found in Leigh Syndrome, confirming that acute MPTP intoxicated mice are a good model of Leigh Syndrome.

Modulation of Respiratory Frequency by Peptidergic Input to Rhythmogenic Neurons in the PreBötzinger Complex

PubMed Central

Gray, Paul A.; Rekling, Jens C.; Bocchiaro, Christopher M.; Feldman, Jack L.

2010-01-01

Neurokinin-1 receptor (NK1R) and μ-opioid receptor (μOR) agonists affected respiratory rhythm when injected directly into the preBötzinger Complex (preBötC), the hypothesized site for respiratory rhythmogenesis in mammals. These effects were mediated by actions on preBötC rhythmogenic neurons. The distribution of NK1R+ neurons anatomically defined the preBötC. Type 1 neurons in the preBötC, which have rhythmogenic properties, expressed both NK1Rs and μORs, whereas type 2 neurons expressed only NK1Rs. These findings suggest that the preBötC is a definable anatomic structure with unique physiological function and that a subpopulation of neurons expressing both NK1Rs and μORs generate respiratory rhythm and modulate respiratory frequency. PMID:10567264

Tissuelike 3D Assemblies of Human Broncho-Epithelial Cells

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.

2010-01-01

Three-dimensional (3D) tissuelike assemblies (TLAs) of human broncho-epithelial (HBE) cells have been developed for use in in vitro research on infection of humans by respiratory viruses. The 2D monolayer HBE cell cultures heretofore used in such research lack the complex cell structures and interactions characteristic of in vivo tissues and, consequently, do not adequately emulate the infection dynamics of in-vivo microbial adhesion and invasion. In contrast, the 3D HBE TLAs are characterized by more-realistic reproductions of the geometrical and functional complexity, differentiation of cells, cell-to-cell interactions, and cell-to-matrix interactions characteristic of human respiratory epithelia. Hence, the 3D HBE TLAs are expected to make it possible to perform at least some of the research in vitro under more-realistic conditions, without need to infect human subjects. The TLAs are grown on collagen-coated cyclodextran microbeads under controlled conditions in a nutrient liquid in the simulated microgravitational environment of a bioreactor of the rotating- wall-vessel type. Primary human mesenchymal bronchial-tracheal cells are used as a foundation matrix, while adult human bronchial epithelial immortalized cells are used as the overlying component. The beads become coated with cells, and cells on adjacent beads coalesce into 3D masses. The resulting TLAs have been found to share significant characteristics with in vivo human respiratory epithelia including polarization, tight junctions, desmosomes, and microvilli. The differentiation of the cells in these TLAs into tissues functionally similar to in vivo tissues is confirmed by the presence of compounds, including villin, keratins, and specific lung epithelium marker compounds, and by the production of tissue mucin. In a series of initial infection tests, TLA cultures were inoculated with human respiratory syncytial viruses and parainfluenza type 3 viruses. Infection was confirmed by photomicrographs that showed signs of damage by viruses and virus titers (see figure) that indicated large increases in the populations of viruses during the days following inoculation.

Respiratory Chain Complexes in Dynamic Mitochondria Display a Patchy Distribution in Life Cells

PubMed Central

Muster, Britta; Kohl, Wladislaw; Wittig, Ilka; Strecker, Valentina; Joos, Friederike; Haase, Winfried; Bereiter-Hahn, Jürgen; Busch, Karin

2010-01-01

Background Mitochondria, the main suppliers of cellular energy, are dynamic organelles that fuse and divide frequently. Constraining these processes impairs mitochondrial is closely linked to certain neurodegenerative diseases. It is proposed that functional mitochondrial dynamics allows the exchange of compounds thereby providing a rescue mechanism. Methodology/Principal Findings The question discussed in this paper is whether fusion and fission of mitochondria in different cell lines result in re-localization of respiratory chain (RC) complexes and of the ATP synthase. This was addressed by fusing cells containing mitochondria with respiratory complexes labelled with different fluorescent proteins and resolving their time dependent re-localization in living cells. We found a complete reshuffling of RC complexes throughout the entire chondriome in single HeLa cells within 2–3 h by organelle fusion and fission. Polykaryons of fused cells completely re-mixed their RC complexes in 10–24 h in a progressive way. In contrast to the recently described homogeneous mixing of matrix-targeted proteins or outer membrane proteins, the distribution of RC complexes and ATP synthase in fused hybrid mitochondria, however, was not homogeneous but patterned. Thus, complete equilibration of respiratory chain complexes as integral inner mitochondrial membrane complexes is a slow process compared with matrix proteins probably limited by complete fusion. In co-expressing cells, complex II is more homogenously distributed than complex I and V, resp. Indeed, this result argues for higher mobility and less integration in supercomplexes. Conclusion/Significance Our results clearly demonstrate that mitochondrial fusion and fission dynamics favours the re-mixing of all RC complexes within the chondriome. This permanent mixing avoids a static situation with a fixed composition of RC complexes per mitochondrion. PMID:20689601

Calculation of genomic predicted transmitting abilities for bovine respiratory disease complex in Holsteins

USDA-ARS?s Scientific Manuscript database

Bovine Respiratory Disease Complex is a disease that is very costly to the dairy industry. Genomic selection may be an effective tool to improve host resistance to the pathogens that cause this disease. Use of genomic predicted transmitting abilities (GPTA) for selection has had a dramatic effect on...

Mycobacterium chimaera pulmonary infection complicating cystic fibrosis: a case report.

PubMed

Cohen-Bacrie, Stéphan; David, Marion; Stremler, Nathalie; Dubus, Jean-Christophe; Rolain, Jean-Marc; Drancourt, Michel

2011-09-22

Mycobacterium chimaera is a recently described species within the Mycobacterium avium complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection. An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a Mycobacterium avium complex organism further identified as M. chimaera. Using sequencing-based methods of identification, we observed that M. chimaera organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with M. avium subsp. hominissuis isolates. We believe that M. chimaera should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.

[Monitorization of respiratory mechanics in the ventilated patient].

PubMed

García-Prieto, E; Amado-Rodríguez, L; Albaiceta, G M

2014-01-01

Monitoring during mechanical ventilation allows the measurement of different parameters of respiratory mechanics. Accurate interpretation of these data can be useful for characterizing the situation of the different components of the respiratory system, and for guiding ventilator settings. In this review, we describe the basic concepts of respiratory mechanics, their interpretation, and their potential use in fine-tuning mechanical ventilation. Copyright © 2013 Elsevier España, S.L. y SEMICYUC. All rights reserved.

UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction

PubMed Central

Kazak, Lawrence; Chouchani, Edward T.; Stavrovskaya, Irina G.; Lu, Gina Z.; Jedrychowski, Mark P.; Egan, Daniel F.; Kumari, Manju; Kong, Xingxing; Erickson, Brian K.; Szpyt, John; Rosen, Evan D.; Murphy, Michael P.; Kristal, Bruce S.; Gygi, Steven P.; Spiegelman, Bruce M.

2017-01-01

Brown adipose tissue (BAT) mitochondria exhibit high oxidative capacity and abundant expression of both electron transport chain components and uncoupling protein 1 (UCP1). UCP1 dissipates the mitochondrial proton motive force (Δp) generated by the respiratory chain and increases thermogenesis. Here we find that in mice genetically lacking UCP1, cold-induced activation of metabolism triggers innate immune signaling and markers of cell death in BAT. Moreover, global proteomic analysis reveals that this cascade induced by UCP1 deletion is associated with a dramatic reduction in electron transport chain abundance. UCP1-deficient BAT mitochondria exhibit reduced mitochondrial calcium buffering capacity and are highly sensitive to mitochondrial permeability transition induced by reactive oxygen species (ROS) and calcium overload. This dysfunction depends on ROS production by reverse electron transport through mitochondrial complex I, and can be rescued by inhibition of electron transfer through complex I or pharmacologic depletion of ROS levels. Our findings indicate that the interscapular BAT of Ucp1 knockout mice exhibits mitochondrial disruptions that extend well beyond the deletion of UCP1 itself. This finding should be carefully considered when using this mouse model to examine the role of UCP1 in physiology. PMID:28630339

The epidemiology of bovine respiratory disease: What is the evidence for predisposing factors?

PubMed Central

Taylor, Jared D.; Fulton, Robert W.; Lehenbauer, Terry W.; Step, Douglas L.; Confer, Anthony W.

2010-01-01

Bovine respiratory disease (BRD) is the most costly disease of beef cattle in North America. It is multi-factorial, with a variety of physical and physiological stressors combining to predispose cattle to pneumonia. However, efforts to discern which factors are most important have frequently failed to establish definitive answers. Calves are at highest risk shortly after transport. Risk factors include purchasing from sale barns and commingling. It is unclear whether or not these practices increase susceptibility, increase exposure, or are proxies for poor management. Lighter-weight calves appear to be at greater risk, although this has not been consistent. Persistent infection (PI) with bovine virus diarrhea virus increases BRD occurrence, but it is unclear if PI calves affect other cattle in the feedlot. The complexity of BRD has made it difficult to define involvement of individual factors. Stressors may play a role as “necessary but not sufficient” components, requiring additive effects to cause disease. PMID:21197200

Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity

PubMed Central

Thomas, David C.; Clare, Simon; Sowerby, John M.; Juss, Jatinder K.; Goulding, David A.; van der Weyden, Louise; Prakash, Ananth; Harcourt, Katherine; Mukhopadhyay, Subhankar; Antrobus, Robin; Bateman, Alex

2017-01-01

The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91phox and p22phox subunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse gene bc017643, and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91phox and p22phox. Consequently, Eros-deficient mice quickly succumb to infection. Eros also contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases. Eros is an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense. PMID:28351984

A new mitochondrial point mutation in the transfer RNA(Lys) gene associated with progressive external ophthalmoplegia with impaired respiratory regulation.

PubMed

Wolf, Joachim; Obermaier-Kusser, Bert; Jacobs, Martina; Milles, Cornelia; Mörl, Mario; von Pein, Harald D; Grau, Armin J; Bauer, Matthias F

2012-05-15

We report a novel heteroplasmic point mutation G8299A in the gene for mitochondrial tRNA(Lys) in a patient with progressive external ophthalmoplegia complicated by recurrent respiratory insufficiency. Biochemical analysis of respiratory chain complexes in muscle homogenate showed a combined complex I and IV deficiency. The transition does not represent a known neutral polymorphism and affects a position in the tRNA acceptor stem which is conserved in primates, leading to a destabilization of this functionally important domain. In vitro analysis of an essential maturation step of the tRNA transcript indicates the probable pathogenicity of this mutation. We hypothesize that there is a causal relationship between the novel G8299A transition and progressive external ophthalmoplegia with recurrent respiratory failure due to a depressed respiratory drive. Copyright © 2012 Elsevier B.V. All rights reserved.

Equation Discovery for Model Identification in Respiratory Mechanics of the Mechanically Ventilated Human Lung

NASA Astrophysics Data System (ADS)

Ganzert, Steven; Guttmann, Josef; Steinmann, Daniel; Kramer, Stefan

Lung protective ventilation strategies reduce the risk of ventilator associated lung injury. To develop such strategies, knowledge about mechanical properties of the mechanically ventilated human lung is essential. This study was designed to develop an equation discovery system to identify mathematical models of the respiratory system in time-series data obtained from mechanically ventilated patients. Two techniques were combined: (i) the usage of declarative bias to reduce search space complexity and inherently providing the processing of background knowledge. (ii) A newly developed heuristic for traversing the hypothesis space with a greedy, randomized strategy analogical to the GSAT algorithm. In 96.8% of all runs the applied equation discovery system was capable to detect the well-established equation of motion model of the respiratory system in the provided data. We see the potential of this semi-automatic approach to detect more complex mathematical descriptions of the respiratory system from respiratory data.

Closed Genome Sequences of Seven Histophilus somni Isolates from Beef Calves with Bovine Respiratory Disease Complex.

PubMed

Harhay, Gregory P; Harhay, Dayna M; Bono, James L; Smith, Timothy P L; Capik, Sarah F; DeDonder, Keith D; Apley, Michael D; Lubbers, Brian V; White, Bradley J; Larson, Robert L

2017-10-05

Histophilus somni is a fastidious Gram-negative opportunistic pathogenic Pasteurellaceae that affects multiple organ systems and is one of the principal bacterial species contributing to bovine respiratory disease complex (BRDC) in feed yard cattle. Here, we present seven closed genome sequences isolated from three beef calves showing sign of BRDC.

Evaluating the metagenome of two sampling locations in the nasal cavity of cattle with bovine respiratory disease complex

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a multi-factor disease, and disease incidence may be associated with an animal’s commensal microbiota (metagenome). Evaluation of the animal’s resident microbiota in the nasal cavity may help us to understand the impact of the metagenome on incidence of ...

Evaluating the microbiome of two sampling locations in the nasal cavity of cattle with bovine respiratory disease complex (BRDC)

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is a multi-factor disease, and disease incidence may be associated with an animal’s commensal microbiota (metagenome). Evaluation of the animal’s resident microbiota in the nasal cavity may help us to understand the impact of the metagenome on incidence of ...

Real-time optical studies of respiratory Complex I turnover.

PubMed

Belevich, Nikolai; Belevich, Galina; Verkhovskaya, Marina

2014-12-01

Reduction of Complex l (NADH:ubiquinone oxidoreductase l) from Escherichia coli by NADH was investigated optically by means of an ultrafast stopped-flow approach. A locally designed microfluidic stopped-flow apparatus with a low volume (0.21Jl) but a long optical path (10 mm) cuvette allowed measurements in the time range from 270 ).IS to seconds. The data acquisition system collected spectra in the visible range every 50 )JS. Analysis of the obtained time-resolved spectral changes upon the reaction of Complex I with NADH revealed three kinetic components with characteristic times of <270 ).IS, 0.45-0.9 ms and 3-6 ms, reflecting reduction of different FeS clusters and FMN. The rate of the major ( T = 0.45-0.9 ms) component was slower than predicted by electron transfer theory for the reduction of all FeS clusters in the intraprotein redox chain. This delay of the reaction was explained by retention of NAD+ in the catalytic site. The fast optical changes in the time range of 0.27- 1.5 ms were not altered significantly in the presence of 1 0-fold excess of NAD+ over NADH. The data obtained on the NuoF E95Q variant of Complex I shows that the single amino acid replacement in the catalytic site caused a strong decrease of NADH binding and/or the hydride transfer from bound NADH to FMN.

Loss of protohaem IX farnesyltransferase in mature dentate granule cells impairs short-term facilitation at mossy fibre to CA3 pyramidal cell synapses.

PubMed

Booker, Sam A; Campbell, Graham R; Mysiak, Karolina S; Brophy, Peter J; Kind, Peter C; Mahad, Don J; Wyllie, David J A

2017-03-15

Neurodegenerative disorders can exhibit dysfunctional mitochondrial respiratory chain complex IV activity. Conditional deletion of cytochrome c oxidase, the terminal enzyme in the respiratory electron transport chain of mitochondria, from hippocampal dentate granule cells in mice does not affect low-frequency dentate to CA3 glutamatergic synaptic transmission. High-frequency dentate to CA3 glutamatergic synaptic transmission and feedforward inhibition are significantly attenuated in cytochrome c oxidase-deficient mice. Intact presynaptic mitochondrial function is critical for the short-term dynamics of mossy fibre to CA3 synaptic function. Neurodegenerative disorders are characterized by peripheral and central symptoms including cognitive impairments which have been associated with reduced mitochondrial function, in particular mitochondrial respiratory chain complex IV or cytochrome c oxidase activity. In the present study we conditionally removed a key component of complex IV, protohaem IX farnesyltransferase encoded by the COX10 gene, in granule cells of the adult dentate gyrus. Utilizing whole-cell patch-clamp recordings from morphologically identified CA3 pyramidal cells from control and complex IV-deficient mice, we found that reduced mitochondrial function did not result in overt deficits in basal glutamatergic synaptic transmission at the mossy-fibre synapse because the amplitude, input-output relationship and 50 ms paired-pulse facilitation were unchanged following COX10 removal from dentate granule cells. However, trains of stimuli given at high frequency (> 20 Hz) resulted in dramatic reductions in short-term facilitation and, at the highest frequencies (> 50 Hz), also reduced paired-pulse facilitation, suggesting a requirement for adequate mitochondrial function to maintain glutamate release during physiologically relevant activity patterns. Interestingly, local inhibition was reduced, suggesting the effect observed was not restricted to synapses with CA3 pyramidal cells via large mossy-fibre boutons, but rather to all synapses formed by dentate granule cells. Therefore, presynaptic mitochondrial function is critical for the short-term dynamics of synapse function, which may contribute to the cognitive deficits observed in pathological mitochondrial dysfunction. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Exercise training improves vascular mitochondrial function

PubMed Central

Park, Song-Young; Rossman, Matthew J.; Gifford, Jayson R.; Bharath, Leena P.; Bauersachs, Johann; Richardson, Russell S.; Abel, E. Dale; Symons, J. David

2016-01-01

Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels of peroxisome proliferative activated receptor-γ coactivator-1α and the downstream targets cytochrome c oxidase subunit IV isoform 1, isocitrate dehydrogenase (Idh) 2, and Idh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser1177), and suppressed reactive oxygen species generation (all P < 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function. PMID:26825520

Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta

PubMed Central

Samara, Ziyad; Fiamma, Marie-Noëlle; Bautin, Nathalie; Ranohavimparany, Anja; Le Coz, Patrick; Golmard, Jean-Louis; Darré, Pierre; Zelter, Marc; Poon, Chi-Sang; Similowski, Thomas

2011-01-01

Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [Rana (Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- (n = 8) and postmetamorphic tadpoles (n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development (P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only (P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 (P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 (P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals. PMID:21325645

Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta.

PubMed

Straus, Christian; Samara, Ziyad; Fiamma, Marie-Noëlle; Bautin, Nathalie; Ranohavimparany, Anja; Le Coz, Patrick; Golmard, Jean-Louis; Darré, Pierre; Zelter, Marc; Poon, Chi-Sang; Similowski, Thomas

2011-05-01

Human ventilation at rest exhibits mathematical chaos-like complexity that can be described as long-term unpredictability mediated (in whole or in part) by some low-dimensional nonlinear deterministic process. Although various physiological and pathological situations can affect respiratory complexity, the underlying mechanisms remain incompletely elucidated. If such chaos-like complexity is an intrinsic property of central respiratory generators, it should appear or increase when these structures mature or are stimulated. To test this hypothesis, we employed the isolated tadpole brainstem model [Rana (Pelophylax) esculenta] and recorded the neural respiratory output (buccal and lung rhythms) of pre- (n = 8) and postmetamorphic tadpoles (n = 8), at physiologic (7.8) and acidic pH (7.4). We analyzed the root mean square of the cranial nerve V or VII neurograms. Development and acidosis had no effect on buccal period. Lung frequency increased with development (P < 0.0001). It also increased with acidosis, but in postmetamorphic tadpoles only (P < 0.05). The noise-titration technique evidenced low-dimensional nonlinearities in all the postmetamorphic brainstems, at both pH. Chaos-like complexity, assessed through the noise limit, increased from pH 7.8 to pH 7.4 (P < 0.01). In contrast, linear models best fitted the ventilatory rhythm in all but one of the premetamorphic preparations at pH 7.8 (P < 0.005 vs. postmetamorphic) and in four at pH 7.4 (not significant vs. postmetamorphic). Therefore, in a lower vertebrate model, the brainstem respiratory central rhythm generator accounts for ventilatory chaos-like complexity, especially in the postmetamorphic stage and at low pH. According to the ventilatory generators homology theory, this may also be the case in mammals.

Growth of functional cranial components in rats submitted to intergenerational undernutrition

PubMed Central

Cesani, María F; Orden, Alicia B; Oyhenart, Evelia E; Zucchi, Mariel; Muñe, María C; Pucciarelli, Héctor M

2006-01-01

The aim of the present study was to discover how intergenerational undernutrition affects the growth of major and minor functional cranial components in two generations of rats. Control animals constituted the parental generation (P). The undernourished generations (F1 and F2) were fed 75% of the control diet. Animals were X-rayed every 10 days from 20 to 100 days of age. The length, width and height of the major (neurocranium and splanchnocranium) and minor (anterior-neural, middle-neural, posterior-neural, otic, respiratory, masticatory and alveolar) cranial components were measured on each radiograph. Volumetric indices were calculated to estimate size variations of these components. Data were processed using the Kruskal–Wallis and Kolmogorov–Smirnov tests for two samples. Impairment in splanchnocranial and neurocranial growth was found, the latter being more affected than the former in F1. Comparison between F2 and F1 animals showed cumulative effects of undernutrition in both major and minor components (anterior-neural, respiratory, masticatory and alveolar in males, and middle-neural and respiratory in females). Such differential effects on minor components may reflect a residual mechanical strain resulting from the linkage between components. This phenomenon was clearly observed in the neurocranium and could be understood as an adaptive response to the demands of the associated functional matrices. PMID:16879595

The use of facemasks to prevent respiratory infection: a literature review in the context of the Health Belief Model

PubMed Central

Sim, Shin Wei; Moey, Kirm Seng Peter; Tan, Ngiap Chuan

2014-01-01

INTRODUCTION Acute respiratory infections are prevalent and pose a constant threat to society. While the use of facemasks has proven to be an effective barrier to curb the aerosol spread of such diseases, its use in the local community is uncommon, resulting in doubts being cast on its effectiveness in preventing airborne infections during epidemics. We thus aimed to conduct a literature review to determine the factors that influence the use of facemasks as a primary preventive health measure in the community. METHODS A search for publications relating to facemask usage was performed on Medline, PubMed, Google, World Health Organization and Singapore government agencies’ websites, using search terms such as ‘facemask’, ‘mask’, ‘influenza’, ‘respiratory infection’, ‘personal protective equipment’, ‘disease prevention’, ‘compliance’ and ‘adherence’. Findings were framed under five components of the Health Belief Model perceived susceptibility, perceived benefits, perceived severity, perceived barriers and cues to action. RESULTS We found that individuals are more likely to wear facemasks due to the perceived susceptibility and perceived severity of being afflicted with life-threatening diseases. Although perceived susceptibility appeared to be the most significant factor determining compliance, perceived benefits of mask-wearing was found to have significant effects on mask-wearing compliance as well. Perceived barriers include experience or perception of personal discomfort and sense of embarrassment. Media blitz and public health promotion activities supported by government agencies provide cues to increase the public’s usage of facemasks. CONCLUSION Complex interventions that use multipronged approaches targeting the five components of the Health Belief Model, especially perceived susceptibility, are needed to increase the use of facemasks in the community. Further studies are required to evaluate the effectiveness of implemented interventions. PMID:24664384

Effective deployment of technology-supported management of chronic respiratory conditions: a call for stakeholder engagement.

PubMed

Costello, Richard W; Dima, Alexandra L; Ryan, Dermot; McIvor, R Andrew; Boycott, Kay; Chisholm, Alison; Price, David; Blakey, John D

2017-01-01

Healthcare systems are under increasing strain, predominantly due to chronic non-communicable diseases. Connected healthcare technologies are becoming ever more capable and their components cheaper. These innovations could facilitate both self-management and more efficient use of healthcare resources for common respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, newer technologies can only facilitate major changes in practice, and cannot accomplish them in isolation. There are now large numbers of devices and software offerings available. However, the potential of such technologies is not being realised due to limited engagement with the public, clinicians and providers, and a relative paucity of evidence describing elements of best practice in this complex and evolving environment. Indeed, there are clear examples of wasted resources and potential harm. We therefore call on interested parties to work collaboratively to begin to realize the potential benefits and reduce the risks of connected technologies through change in practice. We highlight key areas where such partnership can facilitate the effective and safe use of technology in chronic respiratory care: developing data standards and fostering inter-operability, making collaborative testing facilities available at scale for small to medium enterprises, developing and promoting new adaptive trial designs, developing robust health economic models, agreeing expedited approval pathways, and detailed planning of dissemination to use. The increasing capability and availability of connected technologies in respiratory care offers great opportunities and significant risks. A co-ordinated collaborative approach is needed to realize these benefits at scale. Using newer technologies to revolutionize practice relies on widespread engagement and cannot be delivered by a minority of interested specialists. Failure to engage risks a costly and inefficient chapter in respiratory care.

Effective deployment of technology-supported management of chronic respiratory conditions: a call for stakeholder engagement

PubMed Central

Costello, Richard W; Dima, Alexandra L; Ryan, Dermot; McIvor, R Andrew; Boycott, Kay; Chisholm, Alison; Price, David; Blakey, John D

2017-01-01

Background Healthcare systems are under increasing strain, predominantly due to chronic non-communicable diseases. Connected healthcare technologies are becoming ever more capable and their components cheaper. These innovations could facilitate both self-management and more efficient use of healthcare resources for common respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, newer technologies can only facilitate major changes in practice, and cannot accomplish them in isolation. Focus of review There are now large numbers of devices and software offerings available. However, the potential of such technologies is not being realised due to limited engagement with the public, clinicians and providers, and a relative paucity of evidence describing elements of best practice in this complex and evolving environment. Indeed, there are clear examples of wasted resources and potential harm. We therefore call on interested parties to work collaboratively to begin to realize the potential benefits and reduce the risks of connected technologies through change in practice. We highlight key areas where such partnership can facilitate the effective and safe use of technology in chronic respiratory care: developing data standards and fostering inter-operability, making collaborative testing facilities available at scale for small to medium enterprises, developing and promoting new adaptive trial designs, developing robust health economic models, agreeing expedited approval pathways, and detailed planning of dissemination to use. Conclusion The increasing capability and availability of connected technologies in respiratory care offers great opportunities and significant risks. A co-ordinated collaborative approach is needed to realize these benefits at scale. Using newer technologies to revolutionize practice relies on widespread engagement and cannot be delivered by a minority of interested specialists. Failure to engage risks a costly and inefficient chapter in respiratory care. PMID:28740444

Identification of a multi-protein reductive dehalogenase complex in Dehalococcoides mccartyi strain CBDB1 suggests a protein-dependent respiratory electron transport chain obviating quinone involvement.

PubMed

Kublik, Anja; Deobald, Darja; Hartwig, Stefanie; Schiffmann, Christian L; Andrades, Adarelys; von Bergen, Martin; Sawers, R Gary; Adrian, Lorenz

2016-09-01

Dehalococcoides mccartyi strain CBDB1 is an obligate organohalide-respiring bacterium using only hydrogen as electron donor and halogenated organics as electron acceptor. Here, we studied proteins involved in the respiratory chain under non-denaturing conditions. Using blue native gel electrophoresis (BN-PAGE), gel filtration and ultrafiltration an active dehalogenating protein complex with a molecular mass of 250-270 kDa was identified. The active subunit of reductive dehalogenase (RdhA) colocalised with a complex iron-sulfur molybdoenzyme (CISM) subunit (CbdbA195) and an iron-sulfur cluster containing subunit (CbdbA131) of the hydrogen uptake hydrogenase (Hup). No colocalisation between the catalytically active subunits of hydrogenase and reductive dehalogenase was found. By two-dimensional BN/SDS-PAGE the stability of the complex towards detergents was assessed, demonstrating stepwise disintegration with increasing detergent concentrations. Chemical cross-linking confirmed the presence of a higher molecular mass reductive dehalogenase protein complex composed of RdhA, CISM I and Hup hydrogenase and proved to be a potential tool for stabilising protein-protein interactions of the dehalogenating complex prior to membrane solubilisation. Taken together, the identification of the respiratory dehalogenase protein complex and the absence of indications for quinone participation in the respiration suggest a quinone-independent protein-based respiratory electron transfer chain in D. mccartyi. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Indigenous knowledge of pastoralists on respiratory diseases of camels in northern Kenya.

PubMed

Wako, D D; Younan, M; Tessema, T S; Glücks, I V; Baumann, M P O

2016-08-01

The camel disease terminology of pastoralists in northern Kenya differentiates between two respiratory disease complexes of camels. Participatory epidemiology data were collected in 2011 in three camel keeping communities (Gabra, Garri, and Somali) and analysed to assess the validity of this differentiation. Further queries assessed recurrence of the disease in the same animal, most affected age group, relative frequency of occurrence, morbidity rates, mortality rates and response to antibiotic treatment. Based on matrix scoring the cardinal symptom nasal discharge was significantly correlated with Respiratory Disease Complex 1 (RDC1; Somali Hergeb, Gabra & Garri Furri) while cough was correlated with Respiratory Disease Complex 2 (RDC2; Somali Dhuguta, Gabra Qufa, Garri Dhugud). RDC1 appears to occur regularly every year and does not respond to antibiotic treatments while outbreaks of RDC2 are only observed at intervals of several years and treated cases do generally respond to antibiotics. While RDC1 is more severe in calves, RDC 2 is mostly associated with respiratory disease in adults. Elements of this differentiation appear to be in agreement with other authors who differentiate between camel influenza (PI3 virus) and bacterial camel pneumonia, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Advanced Respiratory Motion Compensation for Coronary MR Angiography

PubMed Central

Henningsson, Markus; Botnar, Rene M.

2013-01-01

Despite technical advances, respiratory motion remains a major impediment in a substantial amount of patients undergoing coronary magnetic resonance angiography (CMRA). Traditionally, respiratory motion compensation has been performed with a one-dimensional respiratory navigator positioned on the right hemi-diaphragm, using a motion model to estimate and correct for the bulk respiratory motion of the heart. Recent technical advancements has allowed for direct respiratory motion estimation of the heart, with improved motion compensation performance. Some of these new methods, particularly using image-based navigators or respiratory binning, allow for more advanced motion correction which enables CMRA data acquisition throughout most or all of the respiratory cycle, thereby significantly reducing scan time. This review describes the three components typically involved in most motion compensation strategies for CMRA, including respiratory motion estimation, gating and correction, and how these processes can be utilized to perform advanced respiratory motion compensation. PMID:23708271

Structural basis for energy transduction by respiratory alternative complex III.

PubMed

Sousa, Joana S; Calisto, Filipa; Langer, Julian D; Mills, Deryck J; Refojo, Patrícia N; Teixeira, Miguel; Kühlbrandt, Werner; Vonck, Janet; Pereira, Manuela M

2018-04-30

Electron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell. Prokaryotes can use a wide range of electron donors and acceptors and may have alternative complexes performing the same catalytic reactions as the mitochondrial complexes. This is the case for the alternative complex III (ACIII), a quinol:cytochrome c/HiPIP oxidoreductase. In order to understand the catalytic mechanism of this respiratory enzyme, we determined the structure of ACIII from Rhodothermus marinus at 3.9 Å resolution by single-particle cryo-electron microscopy. ACIII presents a so-far unique structure, for which we establish the arrangement of the cofactors (four iron-sulfur clusters and six c-type hemes) and propose the location of the quinol-binding site and the presence of two putative proton pathways in the membrane. Altogether, this structure provides insights into a mechanism for energy transduction and introduces ACIII as a redox-driven proton pump.

A high-throughput screen for single gene activities: isolation of apoptosis inducers.

PubMed

Albayrak, Timur; Grimm, Stefan

2003-05-16

We describe a novel genetic screen that is performed by transfecting every individual clone of an expression library into a separate population of cells in a high-throughput mode. The screen allows one to achieve a hitherto unattained sensitivity in expression cloning which was exploited in a first read-out to clone apoptosis-inducing genes. This led to the isolation of several genes whose proteins induce distinct phenotypes of apoptosis in 293T cells. One of the isolated genes is the tumor suppressor cytochrome b(L) (cybL), a component of the respiratory chain complex II, that diminishes the activity of this complex for apoptosis induction. This gene is more efficient and specific for causing cell death than a drug with the same activity. These results suggest further applications, both of the isolated genes and the screen.

[Pathophysiology of respiratory muscle weakness].

PubMed

Windisch, W

2008-03-01

The respiratory system consists of two parts which can be impaired independently from each other, the lungs and the respiratory pump. The latter is a complex system covering different anatomic structures: the breathing centre, the peripheral nervous system, the respiratory muscles, and the thorax. According to this complexity several underlying conditions can cause insufficiency of the respiratory pump, i. e. ventilatory failure. Disturbances of the breathing centre, different neuromuscular disorders, impairments of the mechanics, such as thoracic deformities or hyperinflation, and airway obstruction are example conditions responsible for ventilatory failure. Main characteristic of ventilatory failure is the occurrence of hypercapnia which is in contrast to pulmonary failure where diffusion disturbances typically not cause hypercapnia. Both acute and chronic ventilatory failure presenting with hypercapnia can develop. In acute ventilatory failure respiratory acidosis develops, but in chronic respiratory failure pH is normalized as a consequence of metabolic retention of bicarbonate. However, acute on chronic ventilatory failure can present with a combined picture, i. e. elevated bicarbonate levels, acidosis, and often severe hypercapnia. Clinical signs such as tachypnea, features of the underlying disease or hypercapnia are important diagnostic tools in addition to the measurement of pressures generated by the respiratory muscles. Non-invasive and widely available techniques, such as the assessment of the maximal ins- and expiratory mouth pressures (PImax, PEmax), should be used as screening instruments, but the reliability of these measurements is reduced due to the volitional character of the tests and due to the impossibility to define normal values. Inspiratory pressures can be assessed more accurately and independently from the patients' effort: with or without the insertion of oesophageal and gastric balloon catheters. However, this technique is more invasive and very complex. It is therefore restricted to centres with scientific aims.

Respiratory health effects of air pollution: update on biomass smoke and traffic pollution.

PubMed

Laumbach, Robert J; Kipen, Howard M

2012-01-01

Mounting evidence suggests that air pollution contributes to the large global burden of respiratory and allergic diseases, including asthma, chronic obstructive pulmonary disease, pneumonia, and possibly tuberculosis. Although associations between air pollution and respiratory disease are complex, recent epidemiologic studies have led to an increased recognition of the emerging importance of traffic-related air pollution in both developed and less-developed countries, as well as the continued importance of emissions from domestic fires burning biomass fuels, primarily in the less-developed world. Emissions from these sources lead to personal exposures to complex mixtures of air pollutants that change rapidly in space and time because of varying emission rates, distances from source, ventilation rates, and other factors. Although the high degree of variability in personal exposure to pollutants from these sources remains a challenge, newer methods for measuring and modeling these exposures are beginning to unravel complex associations with asthma and other respiratory tract diseases. These studies indicate that air pollution from these sources is a major preventable cause of increased incidence and exacerbation of respiratory disease. Physicians can help to reduce the risk of adverse respiratory effects of exposure to biomass and traffic air pollutants by promoting awareness and supporting individual and community-level interventions. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex.

PubMed

Kishimoto, Mai; Tsuchiaka, Shinobu; Rahpaya, Sayed Samim; Hasebe, Ayako; Otsu, Keiko; Sugimura, Satoshi; Kobayashi, Suguru; Komatsu, Natsumi; Nagai, Makoto; Omatsu, Tsutomu; Naoi, Yuki; Sano, Kaori; Okazaki-Terashima, Sachiko; Oba, Mami; Katayama, Yukie; Sato, Reiichiro; Asai, Tetsuo; Mizutani, Tetsuya

2017-03-18

Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.

The Mitochondrial Disulfide Relay System Protein GFER Is Mutated in Autosomal-Recessive Myopathy with Cataract and Combined Respiratory-Chain Deficiency

PubMed Central

Di Fonzo, Alessio; Ronchi, Dario; Lodi, Tiziana; Fassone, Elisa; Tigano, Marco; Lamperti, Costanza; Corti, Stefania; Bordoni, Andreina; Fortunato, Francesco; Nizzardo, Monica; Napoli, Laura; Donadoni, Chiara; Salani, Sabrina; Saladino, Francesca; Moggio, Maurizio; Bresolin, Nereo; Ferrero, Iliana; Comi, Giacomo P.

2009-01-01

A disulfide relay system (DRS) was recently identified in the yeast mitochondrial intermembrane space (IMS) that consists of two essential components: the sulfhydryl oxidase Erv1 and the redox-regulated import receptor Mia40. The DRS drives the import of cysteine-rich proteins into the IMS via an oxidative folding mechanism. Erv1p is reoxidized within this system, transferring its electrons to molecular oxygen through interactions with cytochrome c and cytochrome c oxidase (COX), thereby linking the DRS to the respiratory chain. The role of the human Erv1 ortholog, GFER, in the DRS has been poorly explored. Using homozygosity mapping, we discovered that a mutation in the GFER gene causes an infantile mitochondrial disorder. Three children born to healthy consanguineous parents presented with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. The consequences of the mutation at the level of the patient's muscle tissue and fibroblasts were 1) a reduction in complex I, II, and IV activity; 2) a lower cysteine-rich protein content; 3) abnormal ultrastructural morphology of the mitochondria, with enlargement of the IMS space; and 4) accelerated time-dependent accumulation of multiple mtDNA deletions. Moreover, the Saccharomyces cerevisiae erv1R182H mutant strain reproduced the complex IV activity defect and exhibited genetic instability of the mtDNA and mitochondrial morphological defects. These findings shed light on the mechanisms of mitochondrial biogenesis, establish the role of GFER in the human DRS, and promote an understanding of the pathogenesis of a new mitochondrial disease. PMID:19409522

Biallelic C1QBP Mutations Cause Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies.

PubMed

Feichtinger, René G; Oláhová, Monika; Kishita, Yoshihito; Garone, Caterina; Kremer, Laura S; Yagi, Mikako; Uchiumi, Takeshi; Jourdain, Alexis A; Thompson, Kyle; D'Souza, Aaron R; Kopajtich, Robert; Alston, Charlotte L; Koch, Johannes; Sperl, Wolfgang; Mastantuono, Elisa; Strom, Tim M; Wortmann, Saskia B; Meitinger, Thomas; Pierre, Germaine; Chinnery, Patrick F; Chrzanowska-Lightowlers, Zofia M; Lightowlers, Robert N; DiMauro, Salvatore; Calvo, Sarah E; Mootha, Vamsi K; Moggio, Maurizio; Sciacco, Monica; Comi, Giacomo P; Ronchi, Dario; Murayama, Kei; Ohtake, Akira; Rebelo-Guiomar, Pedro; Kohda, Masakazu; Kang, Dongchon; Mayr, Johannes A; Taylor, Robert W; Okazaki, Yasushi; Minczuk, Michal; Prokisch, Holger

2017-10-05

Complement component 1 Q subcomponent-binding protein (C1QBP; also known as p32) is a multi-compartmental protein whose precise function remains unknown. It is an evolutionary conserved multifunctional protein localized primarily in the mitochondrial matrix and has roles in inflammation and infection processes, mitochondrial ribosome biogenesis, and regulation of apoptosis and nuclear transcription. It has an N-terminal mitochondrial targeting peptide that is proteolytically processed after import into the mitochondrial matrix, where it forms a homotrimeric complex organized in a doughnut-shaped structure. Although C1QBP has been reported to exert pleiotropic effects on many cellular processes, we report here four individuals from unrelated families where biallelic mutations in C1QBP cause a defect in mitochondrial energy metabolism. Infants presented with cardiomyopathy accompanied by multisystemic involvement (liver, kidney, and brain), and children and adults presented with myopathy and progressive external ophthalmoplegia. Multiple mitochondrial respiratory-chain defects, associated with the accumulation of multiple deletions of mitochondrial DNA in the later-onset myopathic cases, were identified in all affected individuals. Steady-state C1QBP levels were decreased in all individuals' samples, leading to combined respiratory-chain enzyme deficiency of complexes I, III, and IV. C1qbp -/- mouse embryonic fibroblasts (MEFs) resembled the human disease phenotype by showing multiple defects in oxidative phosphorylation (OXPHOS). Complementation with wild-type, but not mutagenized, C1qbp restored OXPHOS protein levels and mitochondrial enzyme activities in C1qbp -/- MEFs. C1QBP deficiency represents an important mitochondrial disorder associated with a clinical spectrum ranging from infantile lactic acidosis to childhood (cardio)myopathy and late-onset progressive external ophthalmoplegia. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Closed Genome Sequences of Seven Histophilus somni Isolates from Beef Calves with Bovine Respiratory Disease Complex

PubMed Central

Harhay, Dayna M.; Bono, James L.; Smith, Timothy P. L.; Capik, Sarah F.; DeDonder, Keith D.; Apley, Michael D.; Lubbers, Brian V.; White, Bradley J.; Larson, Robert L.

2017-01-01

ABSTRACT Histophilus somni is a fastidious Gram-negative opportunistic pathogenic Pasteurellaceae that affects multiple organ systems and is one of the principal bacterial species contributing to bovine respiratory disease complex (BRDC) in feed yard cattle. Here, we present seven closed genome sequences isolated from three beef calves showing sign of BRDC. PMID:28983006

SAGA complex and Gcn5 are necessary for respiration in budding yeast.

PubMed

Canzonetta, Claudia; Leo, Manuela; Guarino, Salvatore Rocco; Montanari, Arianna; Francisci, Silvia; Filetici, Patrizia

2016-12-01

In budding yeast, growth through fermentation and/or respiration is dependent on the type of carbon source present in the medium. SAGA complex is the main acetylation complex and is required, together with Rtg factors, for nucleus-mitochondria communication and transcriptional activation of specific nuclear genes. Even though acetylation is necessary for mitochondria activity and respiratory pathways the direct role of histone acetyltransferases and SAGA complex has never been investigated directly. In this study we demonstrate, for the first time, that Gcn5 and SAGA are needed for respiratory metabolism and oxygen consumption. According to a central role for acetylation in respiration we find that the Gcn5 inhibitor CPTH2 had higher efficacy on cells grown in glycerol containing media. We also demonstrated that the opposing activities of Gcn5 and Hda1 modify selectively H3-AcK18 and are essential for respiration. Taken together our results suggest a novel paradigm coupling acetyltransferase activity to respiratory metabolism. Correspondingly we propose the selective utilization of KAT inhibitor CPTH2, combined to the modulation of the respiratory metabolism of the cell, as a promising novel tool of intervention in cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Genetic and biochemical findings in Chinese children with Leigh syndrome.

PubMed

Ma, Yan-Yan; Wu, Tong-Fei; Liu, Yu-Peng; Wang, Qiao; Song, Jin-Qing; Li, Xi-Yuan; Shi, Xiu-Yu; Zhang, Wei-Na; Zhao, Meng; Hu, Lin-Yan; Yang, Yan-Ling; Zou, Li-Ping

2013-11-01

This study investigated the genetic and enzymological features of Leigh syndrome due to respiratory chain complex deficiency in Chinese patients. The clinical features of 75 patients were recorded. Mitochondrial respiratory chain enzyme activities were determined via spectrophotometry. Mitochondrial gene sequence analysis was performed in 23 patients. Five core pedigrees were investigated via restriction fragment length polymorphism and gene sequencing. Psychomotor retardation (55%), motor regression (20%), weakness (29%), and epilepsy (25%) were the most frequent manifestations. Sixty-four patients (85.3%) had isolated respiratory complex deficiencies: complex I was seen in 28 patients (37.3%); complex II, seven (9.3%); complex III, six (8%); complex IV, ten (13.3%); and complex V, 13 patients (17.3%). Eleven patients (14.7%) had combined complex deficiencies. Mitochondrial DNA mutations were detected in 10 patients. Eight point mutations were found in mitochondrial structural genes: m.4833A>G in ND2, m.10191T>C in ND3, m.12338T>C and m.13513G>A in ND5, m.14502T>C and m.14487T>C in ND6, m.8108A>G in COXII, and m.8993T>G in ATPase6. Three mutations were found in tRNA genes: m.4395A>G in tRNA-Gln, m.10454T>C in tRNA-Arg, and m.5587T>C in tRNA-Ala. One patient and their mother both had the m.12338T>C and m.8993T>C mutations. In conclusion, mitochondrial respiratory chain complex I deficiency and structural gene mutations frequently occur in Chinese Leigh syndrome patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

The obligate respiratory supercomplex from Actinobacteria.

PubMed

Kao, Wei-Chun; Kleinschroth, Thomas; Nitschke, Wolfgang; Baymann, Frauke; Neehaul, Yashvin; Hellwig, Petra; Richers, Sebastian; Vonck, Janet; Bott, Michael; Hunte, Carola

2016-10-01

Actinobacteria are closely linked to human life as industrial producers of bioactive molecules and as human pathogens. Respiratory cytochrome bcc complex and cytochrome aa3 oxidase are key components of their aerobic energy metabolism. They form a supercomplex in the actinobacterial species Corynebacterium glutamicum. With comprehensive bioinformatics and phylogenetic analysis we show that genes for cyt bcc-aa3 supercomplex are characteristic for Actinobacteria (Actinobacteria and Acidimicrobiia, except the anaerobic orders Actinomycetales and Bifidobacteriales). An obligatory supercomplex is likely, due to the lack of genes encoding alternative electron transfer partners such as mono-heme cyt c. Instead, subunit QcrC of bcc complex, here classified as short di-heme cyt c, will provide the exclusive electron transfer link between the complexes as in C. glutamicum. Purified to high homogeneity, the C. glutamicum bcc-aa3 supercomplex contained all subunits and cofactors as analyzed by SDS-PAGE, BN-PAGE, absorption and EPR spectroscopy. Highly uniform supercomplex particles in electron microscopy analysis support a distinct structural composition. The supercomplex possesses a dimeric stoichiometry with a ratio of a-type, b-type and c-type hemes close to 1:1:1. Redox titrations revealed a low potential bcc complex (Em(ISP)=+160mV, Em(bL)=-291mV, Em(bH)=-163mV, Em(cc)=+100mV) fined-tuned for oxidation of menaquinol and a mixed potential aa3 oxidase (Em(CuA)=+150mV, Em(a/a3)=+143/+317mV) mediating between low and high redox potential to accomplish dioxygen reduction. The generated molecular model supports a stable assembled supercomplex with defined architecture which permits energetically efficient coupling of menaquinol oxidation and dioxygen reduction in one supramolecular entity. Copyright © 2016 Elsevier B.V. All rights reserved.

The impact of emotion on respiratory-related evoked potentials

PubMed Central

von Leupoldt, Andreas; Vovk, Andrea; Bradley, Margaret M.; Keil, Andreas; Lang, Peter J.; Davenport, Paul W.

2013-01-01

Emotion influences the perception of respiratory sensations, although the specific mechanism underlying this modulation is not yet clear. We examined the impact of viewing pleasant, neutral, and unpleasant affective pictures on the respiratory-related evoked potential (RREP) elicited by a short inspiratory occlusion in healthy volunteers. Reduced P3 amplitude of the RREP was found for respiratory probes presented when viewing pleasant or unpleasant series, when compared to those presented during the neutral series. Earlier RREP components, such as Nf, P1, N1, and P2, showed no modulation by emotion. The results suggest that emotion impacts the perception of respiratory sensations by reducing the attentional resources available for processing afferent respiratory sensory signals. PMID:20070570

Real-Time External Respiratory Motion Measuring Technique Using an RGB-D Camera and Principal Component Analysis †

PubMed Central

Wijenayake, Udaya; Park, Soon-Yong

2017-01-01

Accurate tracking and modeling of internal and external respiratory motion in the thoracic and abdominal regions of a human body is a highly discussed topic in external beam radiotherapy treatment. Errors in target/normal tissue delineation and dose calculation and the increment of the healthy tissues being exposed to high radiation doses are some of the unsolicited problems caused due to inaccurate tracking of the respiratory motion. Many related works have been introduced for respiratory motion modeling, but a majority of them highly depend on radiography/fluoroscopy imaging, wearable markers or surgical node implanting techniques. We, in this article, propose a new respiratory motion tracking approach by exploiting the advantages of an RGB-D camera. First, we create a patient-specific respiratory motion model using principal component analysis (PCA) removing the spatial and temporal noise of the input depth data. Then, this model is utilized for real-time external respiratory motion measurement with high accuracy. Additionally, we introduce a marker-based depth frame registration technique to limit the measuring area into an anatomically consistent region that helps to handle the patient movements during the treatment. We achieved a 0.97 correlation comparing to a spirometer and 0.53 mm average error considering a laser line scanning result as the ground truth. As future work, we will use this accurate measurement of external respiratory motion to generate a correlated motion model that describes the movements of internal tumors. PMID:28792468

Design and performance of a respiratory amplitude gating device for PET/CT imaging

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

Chang Guoping; Chang Tingting; Clark, John W. Jr.

2010-04-15

Purpose: Recently, the authors proposed a free-breathing amplitude gating (FBAG) technique for PET/CT scanners. The implementation of this technique required specialized hardware and software components that were specifically designed to interface with commercial respiratory gating devices to generate the necessary triggers required for the FBAG technique. The objective of this technical note is to introduce an in-house device that integrates all the necessary hardware and software components as well as tracks the patient's respiratory motion to realize amplitude gating on PET/CT scanners. Methods: The in-house device is composed of a piezoelectric transducer coupled to a data-acquisition system in order tomore » monitor the respiratory waveform. A LABVIEW program was designed to control the data-acquisition device and inject triggers into the PET list stream whenever the detected respiratory amplitude crossed a predetermined amplitude range. A timer was also programmed to stop the scan when the accumulated time within the selected amplitude range reached a user-set interval. This device was tested using a volunteer and a phantom study. Results: The results from the volunteer and phantom studies showed that the in-house device can detect similar respiratory signals as commercially available respiratory gating systems and is able to generate the necessary triggers to suppress respiratory motion artifacts. Conclusions: The proposed in-house device can be used to implement the FBAG technique in current PET/CT scanners.« less

Respiratory Adaptations in Acid-base Disturbances: Role of Cerebral Fluids,

DTIC Science & Technology

1979-06-19

The respiratory and metabolic components of acid-base homeostasis are defined. A quantitative empirical description of the (incomplete) mutual...literature. Respiratory adaptations in steady acid-base disturbances of metabolic origin (hyperventilation with hypocapnia in primary metabolic acidosis, and...hypoventilation with hypercapnia in metabolic alkalosis ) are analyzed as a function of the acidity of the cerebral fluids (cerebrospinal and cerebral interstitial fluid). (Author)

Structure of the alternative complex III in a supercomplex with cytochrome oxidase.

PubMed

Sun, Chang; Benlekbir, Samir; Venkatakrishnan, Padmaja; Wang, Yuhang; Hong, Sangjin; Hosler, Jonathan; Tajkhorshid, Emad; Rubinstein, John L; Gennis, Robert B

2018-05-01

Alternative complex III (ACIII) is a key component of the respiratory and/or photosynthetic electron transport chains of many bacteria 1-3 . Like complex III (also known as the bc 1 complex), ACIII catalyses the oxidation of membrane-bound quinol and the reduction of cytochrome c or an equivalent electron carrier. However, the two complexes have no structural similarity 4-7 . Although ACIII has eluded structural characterization, several of its subunits are known to be homologous to members of the complex iron-sulfur molybdoenzyme (CISM) superfamily 8 , including the proton pump polysulfide reductase 9,10 . We isolated the ACIII from Flavobacterium johnsoniae with native lipids using styrene maleic acid copolymer 11-14 , both as an independent enzyme and as a functional 1:1 supercomplex with an aa 3 -type cytochrome c oxidase (cyt aa 3 ). We determined the structure of ACIII to 3.4 Å resolution by cryo-electron microscopy and constructed an atomic model for its six subunits. The structure, which contains a [3Fe-4S] cluster, a [4Fe-4S] cluster and six haem c units, shows that ACIII uses known elements from other electron transport complexes arranged in a previously unknown manner. Modelling of the cyt aa 3 component of the supercomplex revealed that it is structurally modified to facilitate association with ACIII, illustrating the importance of the supercomplex in this electron transport chain. The structure also resolves two of the subunits of ACIII that are anchored to the lipid bilayer with N-terminal triacylated cysteine residues, an important post-translational modification found in numerous prokaryotic membrane proteins that has not previously been observed structurally in a lipid bilayer.

Increased Degradation Rates in the Components of the Mitochondrial Oxidative Phosphorylation Chain in the Cerebellum of Old Mice

PubMed Central

Popa-Wagner, Aurel; Sandu, Raluca E.; Cristin, Coman; Uzoni, Adriana; Welle, Kevin A.; Hryhorenko, Jennifer R.; Ghaemmaghami, Sina

2018-01-01

Brain structures differ in the magnitude of age-related neuron loss with the cerebellum being more affected. An underlying cause could be an age-related decline in mitochondrial bioenergetics. Successful aging of mitochondria reflects a balanced turnover of proteins involved in mitochondrial biogenesis and mitophagy. Thus, an imbalance in mitochondrial turnover can contribute to the diminution of cellular function seen during aging. Mitochondrial biogenesis and mitophagy are mediated by a set of proteins including MFN1, MFN2, OPA1, DRP1, FIS1 as well as DMN1l and DNM1, all of which are required for mitochondrial fission. Using N15 labeling, we report that the turnover rates for DMN1l and FIS1 go in opposite directions in the cerebellum of 22-month-old C57BL6j mice as compared to 3-month-old mice. Previous studies have reported decreased turnover rates for the mitochondrial respiratory complexes of aged rodents. In contrast, we found increased turnover rates for mitochondrial proteins of the oxidative phosphorylation chain in the aged mice as compared to young mice. Furthermore, the turnover rate of the components that are most affected by aging –complex III components (ubiquinol cytochrome C oxidoreductase) and complex IV components (cytochrome C oxidase)– was significantly increased in the senescent cerebellum. However, the turnover rates of proteins involved in mitophagy (i.e., the proteasomal and lysosomal degradation of damaged mitochondria) were not significantly altered with age. Overall, our results suggest that an age-related imbalance in the turnover rates of proteins involved in mitochondrial biogenesis and mitophagy (DMN1l, FIS1) in conjunction with an age-related imbalance in the turnover rates of proteins of the complexes III and IV of the electron transfer chain, might impair cerebellar mitochondrial bioenergetics in old mice. PMID:29503614

Deficiency of respiratory chain complex I in Hashimoto thyroiditis.

PubMed

Zimmermann, Franz A; Neureiter, Daniel; Feichtinger, René G; Trost, Andrea; Sperl, Wolfgang; Kofler, Barbara; Mayr, Johannes A

2016-01-01

Oncocytic cells (OCs) are characterized by an accumulation of mitochondria and their occurrence in the thyroid gland of patients with Hashimoto thyroiditis (HT) is well known. However, their properties and functional relevance are poorly understood. We investigated OC lesions (n=212) in the thyroid of 12 HT patients. Loss of complex I protein was observed in oncocytic lesions of each of the patients. In addition to isolated complex I deficiency, 25% of oncocytic lesions showed combined deficiency of complex I and IV. Thus, we demonstrate for the first time a defect of respiratory chain complex I in OCs of HT patients. Copyright © 2015 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Respiratory Health Effects of Large Animal Farming Environments

PubMed Central

May, Sara; Romberger, Debra J.; Poole, Jill A.

2014-01-01

With increases in large animal-feeding operations to meet consumer demand, adverse upper and lower respiratory health effects in exposed agriculture workers is a concern. The aim of this study was to review large animal confinement feeding operational exposures associated with respiratory disease with focus on recent advances in the knowledge of causative factors and cellular and immunological mechanisms. A PubMed search was conducted with the following keywords: airway, farm, swine, dairy, horse, cattle inflammation, organic dust, endotoxin, and peptidoglycan that were published between 1980 and current. Articles were selected based on their relevance to environmental exposure and reference to airway diseases. Airway diseases included rhinitis, sinusitis, mucus membrane inflammation syndrome, asthma, chronic bronchitis, chronic obstructive pulmonary disease, hypersensitivity pneumonitis, and organic dust toxic syndrome. There is lower prevalence of IgE-mediated asthma and atopy in farmers and their children, but organic dust worsens existing asthma. Multiple etiologic factors are linked to disease including allergens, organic dusts, endotoxins, peptidoglycans and gases. Large animal confinement feeding operations contain a wide-diversity of microbes with increasing focus on Gram-positive bacteria and archeabacteria as opposed to Gram-negative bacteria in mediating disease. Toll-like receptors (TLR) and nucleotide oligomerization domain (NOD)-like innate immune pathways respond to these exposures. Finally, a chronic inflammatory adaptation, tolerance-like response in chronically exposed workers occurs. Large animal confinement farming exposures produces a wide spectrum of upper and lower respiratory tract diseases due to the complex diversity of organic dust, particulates, microbial cell wall components and gases and resultant activation of various innate immune receptor signaling pathways. PMID:23199220

Networks within networks: The neuronal control of breathing

PubMed Central

Garcia, Alfredo J.; Zanella, Sebastien; Koch, Henner; Doi, Atsushi; Ramirez, Jan-Marino

2013-01-01

Breathing emerges through complex network interactions involving neurons distributed throughout the nervous system. The respiratory rhythm generating network is composed of micro networks functioning within larger networks to generate distinct rhythms and patterns that characterize breathing. The pre-Bötzinger complex, a rhythm generating network located within the ventrolateral medulla assumes a core function without which respiratory rhythm generation and breathing cease altogether. It contains subnetworks with distinct synaptic and intrinsic membrane properties that give rise to different types of respiratory rhythmic activities including eupneic, sigh, and gasping activities. While critical aspects of these rhythmic activities are preserved when isolated in in vitro preparations, the pre-Bötzinger complex functions in the behaving animal as part of a larger network that receives important inputs from areas such as the pons and parafacial nucleus. The respiratory network is also an integrator of modulatory and sensory inputs that imbue the network with the important ability to adapt to changes in the behavioral, metabolic, and developmental conditions of the organism. This review summarizes our current understanding of these interactions and relates the emerging concepts to insights gained in other rhythm generating networks. PMID:21333801

Dynamic subcellular localization of a respiratory complex controls bacterial respiration

PubMed Central

Alberge, François; Espinosa, Leon; Seduk, Farida; Sylvi, Léa; Toci, René; Walburger, Anne; Magalon, Axel

2015-01-01

Respiration, an essential process for most organisms, has to optimally respond to changes in the metabolic demand or the environmental conditions. The branched character of their respiratory chains allows bacteria to do so by providing a great metabolic and regulatory flexibility. Here, we show that the native localization of the nitrate reductase, a major respiratory complex under anaerobiosis in Escherichia coli, is submitted to tight spatiotemporal regulation in response to metabolic conditions via a mechanism using the transmembrane proton gradient as a cue for polar localization. These dynamics are critical for controlling the activity of nitrate reductase, as the formation of polar assemblies potentiates the electron flux through the complex. Thus, dynamic subcellular localization emerges as a critical factor in the control of respiration in bacteria. DOI: http://dx.doi.org/10.7554/eLife.05357.001 PMID:26077726

NET formation induced by Pseudomonas aeruginosa cystic fibrosis isolates measured as release of myeloperoxidase-DNA and neutrophil elastase-DNA complexes.

PubMed

Yoo, Dae-goon; Floyd, Madison; Winn, Matthew; Moskowitz, Samuel M; Rada, Balázs

2014-08-01

Cystic fibrosis (CF) airway disease is characterized by Pseudomonas aeruginosa infection and recruitment of neutrophil granulocytes. Neutrophil granule components (myeloperoxidase (MPO), human neutrophil elastase (HNE)), extracellular DNA and P. aeruginosa can all be found in the CF respiratory tract and have all been associated with worsening CF lung function. Pseudomonas-induced formation of neutrophil extracellular traps (NETs) offers a likely mechanism for release of MPO, HNE and DNA from neutrophils. NETs are composed of a DNA backbone decorated with granule proteins like MPO and HNE. Here we sought to examine whether CF clinical isolates of Pseudomonas are capable of inducing NET release from human neutrophil granulocytes. We used two methods to quantify NETs. We modified a previously employed ELISA that detects MPO-DNA complexes and established a new HNE-DNA ELISA. We show that these methods reliably quantify MPO-DNA and HNE-DNA complexes, measures of NET formation. We have found that CF isolates of P. aeruginosa stimulate robust respiratory burst and NET release in human neutrophils. By comparing paired "early" and "late" bacterial isolates obtained from the same CF patient we have found that early isolates induced significantly more NET release than late isolates. Our data support that Pseudomonas-induced NET release represents an important mechanism for release of neutrophil-derived CF inflammatory mediators, and confirm that decreased induction of NET formation is required for long-term adaptation of P. aeruginosa to CF airways. Copyright © 2014 Elsevier B.V. All rights reserved.

The pleiotropic effects of decanoic acid treatment on mitochondrial function in fibroblasts from patients with complex I deficient Leigh syndrome.

PubMed

Kanabus, Marta; Fassone, Elisa; Hughes, Sean David; Bilooei, Sara Farahi; Rutherford, Tricia; Donnell, Maura O'; Heales, Simon J R; Rahman, Shamima

2016-05-01

There is growing interest in the use of the ketogenic diet (KD) to treat inherited metabolic diseases including mitochondrial disorders. However, neither the mechanism whereby the diet may be working, nor if it could benefit all patients with mitochondrial disease, is known. This study focusses on decanoic acid (C10), a component of the medium chain triglyceride KD, and a ligand for the nuclear receptor PPAR-γ known to be involved in mitochondrial biogenesis. The effects of C10 were investigated in primary fibroblasts from a cohort of patients with Leigh syndrome (LS) caused by nuclear-encoded defects of respiratory chain complex I, using mitochondrial respiratory chain enzyme assays, gene expression microarray, qPCR and flow cytometry. Treatment with C10 increased citrate synthase activity, a marker of cellular mitochondrial content, in 50 % of fibroblasts obtained from individuals diagnosed with LS in a PPAR-γ-mediated manner. Gene expression analysis and qPCR studies suggested that treating cells with C10 supports fatty acid metabolism, through increasing ACADVL and CPT1 expression, whilst downregulating genes involved in glucose metabolism (PDK3, PDK4). PCK2, involved in blocking glucose metabolism, was upregulated, as was CAT, encoding catalase. Moreover, treatment with C10 also decreased oxidative stress in complex I deficient (rotenone treated) cells. However, since not all cells from subjects with LS appeared to respond to C10, prior cellular testing in vitro could be employed as a means for selecting individuals for subsequent clinical studies involving C10 preparations.

Tomato Fruit Chromoplasts Behave as Respiratory Bioenergetic Organelles during Ripening1[W][OPEN

PubMed Central

Renato, Marta; Pateraki, Irini; Boronat, Albert; Azcón-Bieto, Joaquín

2014-01-01

During tomato (Solanum lycopersicum) fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts. It was recently reported that tomato chromoplasts can synthesize ATP through a respiratory process called chromorespiration. Here we show that chromoplast oxygen consumption is stimulated by the electron donors NADH and NADPH and is sensitive to octyl gallate (Ogal), a plastidial terminal oxidase inhibitor. The ATP synthesis rate of isolated chromoplasts was dependent on the supply of NAD(P)H and was fully inhibited by Ogal. It was also inhibited by the proton uncoupler carbonylcyanide m-chlorophenylhydrazone, suggesting the involvement of a chemiosmotic gradient. In addition, ATP synthesis was sensitive to 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, a cytochrome b6f complex inhibitor. The possible participation of this complex in chromorespiration was supported by the detection of one of its components (cytochrome f) in chromoplasts using immunoblot and immunocytochemical techniques. The observed increased expression of cytochrome c6 during ripening suggests that it could act as electron acceptor of the cytochrome b6f complex in chromorespiration. The effects of Ogal on respiration and ATP levels were also studied in tissue samples. Oxygen uptake of mature green fruit and leaf tissues was not affected by Ogal, but was inhibited increasingly in fruit pericarp throughout ripening (up to 26% in red fruit). Similarly, Ogal caused a significant decrease in ATP content of red fruit pericarp. The number of energized mitochondria, as determined by confocal microscopy, strongly decreased in fruit tissue during ripening. Therefore, the contribution of chromoplasts to total fruit respiration appears to increase in late ripening stages. PMID:25125503

Macromolecular organization of ATP synthase and complex I in whole mitochondria

PubMed Central

Davies, Karen M.; Strauss, Mike; Daum, Bertram; Kief, Jan H.; Osiewacz, Heinz D.; Rycovska, Adriana; Zickermann, Volker; Kühlbrandt, Werner

2011-01-01

We used electron cryotomography to study the molecular arrangement of large respiratory chain complexes in mitochondria from bovine heart, potato, and three types of fungi. Long rows of ATP synthase dimers were observed in intact mitochondria and cristae membrane fragments of all species that were examined. The dimer rows were found exclusively on tightly curved cristae edges. The distance between dimers along the rows varied, but within the dimer the distance between F1 heads was constant. The angle between monomers in the dimer was 70° or above. Complex I appeared as L-shaped densities in tomograms of reconstituted proteoliposomes. Similar densities were observed in flat membrane regions of mitochondrial membranes from all species except Saccharomyces cerevisiae and identified as complex I by quantum-dot labeling. The arrangement of respiratory chain proton pumps on flat cristae membranes and ATP synthase dimer rows along cristae edges was conserved in all species investigated. We propose that the supramolecular organization of respiratory chain complexes as proton sources and ATP synthase rows as proton sinks in the mitochondrial cristae ensures optimal conditions for efficient ATP synthesis. PMID:21836051

Differential effects of buffer pH on Ca2+-induced ROS emission with inhibited mitochondrial complexes I and III

PubMed Central

Lindsay, Daniel P.; Camara, Amadou K. S.; Stowe, David F.; Lubbe, Ryan; Aldakkak, Mohammed

2015-01-01

Excessive mitochondrial reactive oxygen species (ROS) emission is a critical component in the etiology of ischemic injury. Complex I and complex III of the electron transport chain are considered the primary sources of ROS emission during cardiac ischemia and reperfusion (IR) injury. Several factors modulate ischemic ROS emission, such as an increase in extra-matrix Ca2+, a decrease in extra-matrix pH, and a change in substrate utilization. Here we examined the combined effects of these factors on ROS emission from respiratory complexes I and III under conditions of simulated IR injury. Guinea pig heart mitochondria were suspended in experimental buffer at a given pH and incubated with or without CaCl2. Mitochondria were then treated with either pyruvate, a complex I substrate, followed by rotenone, a complex I inhibitor, or succinate, a complex II substrate, followed by antimycin A, a complex III inhibitor. H2O2 release rate and matrix volume were compared with and without adding CaCl2 and at pH 7.15, 6.9, or 6.5 with pyruvate + rotenone or succinate + antimycin A to simulate conditions that may occur during in vivo cardiac IR injury. We found a large increase in H2O2 release with high [CaCl2] and pyruvate + rotenone at pH 6.9, but not at pHs 7.15 or 6.5. Large increases in H2O2 release rate also occurred at each pH with high [CaCl2] and succinate + antimycin A, with the highest levels observed at pH 7.15. The increases in H2O2 release were associated with significant mitochondrial swelling, and both H2O2 release and swelling were abolished by cyclosporine A, a desensitizer of the mitochondrial permeability transition pore (mPTP). These results indicate that ROS production by complex I and by complex III is differently affected by buffer pH and Ca2+ loading with mPTP opening. The study suggests that changes in the levels of cytosolic Ca2+ and pH during IR alter the relative amounts of ROS produced at mitochondrial respiratory complex I and complex III. PMID:25805998

Streptococcus agalactiae impairs cerebral bioenergetics in experimentally infected silver catfish.

PubMed

Baldissera, Matheus D; Souza, Carine F; Parmeggiani, Belisa S; Santos, Roberto C V; Leipnitz, Guilhian; Moreira, Karen L S; da Rocha, Maria Izabel U M; da Veiga, Marcelo L; Baldisserotto, Bernardo

2017-10-01

It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish (Rhamdia quelen). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of a novel mitochondrial complex I assembly factor ACDH-12 in Caenorhabditis elegans.

PubMed

Chuaijit, Sirithip; Boonyatistan, Worawit; Boonchuay, Pichsinee; Metheetrairut, Chanatip; Suthammarak, Wichit

2018-03-11

Assembly of complex I of the mitochondrial respiratory chain (MRC) requires not only structural subunits for electron transport, but also assembly factors. In the nematode Caenorhabditis elegans, NUAF-1 and NUAF-3 are the only two assembly factors that have been characterized. In this study, we identify ACDH-12 as an assembly factor of the respiratory complex I. We demonstrate for the first time that a deficiency of ACDH-12 affects the formation and function of complex I. RNAi knockdown of acdh-12 also shortens lifespan and decreases fecundity. Although ACDH-12 has long been recognized as a very long-chain acyl-CoA dehydrogenase (VLCAD), the knockdown nematodes did not exhibit any change in body fat content. We suggested that in Caenorhabditis elegans, ACDH-12 is required for the assembly of the respiratory complex I, but may not be crucial to fatty acid oxidation. Interestingly, sequence analysis shows high homology between ACDH-12 and the human ACAD9, a protein that has initially been identified as a VLCAD, but later found to also be involved in the assembly of complex I in human. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Nonlinear dynamics of cardiovascular ageing

PubMed Central

Shiogai, Y.; Stefanovska, A.; McClintock, P.V.E.

2010-01-01

The application of methods drawn from nonlinear and stochastic dynamics to the analysis of cardiovascular time series is reviewed, with particular reference to the identification of changes associated with ageing. The natural variability of the heart rate (HRV) is considered in detail, including the respiratory sinus arrhythmia (RSA) corresponding to modulation of the instantaneous cardiac frequency by the rhythm of respiration. HRV has been intensively studied using traditional spectral analyses, e.g. by Fourier transform or autoregressive methods, and, because of its complexity, has been used as a paradigm for testing several proposed new methods of complexity analysis. These methods are reviewed. The application of time–frequency methods to HRV is considered, including in particular the wavelet transform which can resolve the time-dependent spectral content of HRV. Attention is focused on the cardio-respiratory interaction by introduction of the respiratory frequency variability signal (RFV), which can be acquired simultaneously with HRV by use of a respiratory effort transducer. Current methods for the analysis of interacting oscillators are reviewed and applied to cardio-respiratory data, including those for the quantification of synchronization and direction of coupling. These reveal the effect of ageing on the cardio-respiratory interaction through changes in the mutual modulation of the instantaneous cardiac and respiratory frequencies. Analyses of blood flow signals recorded with laser Doppler flowmetry are reviewed and related to the current understanding of how endothelial-dependent oscillations evolve with age: the inner lining of the vessels (the endothelium) is shown to be of crucial importance to the emerging picture. It is concluded that analyses of the complex and nonlinear dynamics of the cardiovascular system can illuminate the mechanisms of blood circulation, and that the heart, the lungs and the vascular system function as a single entity in dynamical terms. Clear evidence is found for dynamical ageing. PMID:20396667

Nonlinear dynamics of cardiovascular ageing

NASA Astrophysics Data System (ADS)

Shiogai, Y.; Stefanovska, A.; McClintock, P. V. E.

2010-03-01

The application of methods drawn from nonlinear and stochastic dynamics to the analysis of cardiovascular time series is reviewed, with particular reference to the identification of changes associated with ageing. The natural variability of the heart rate (HRV) is considered in detail, including the respiratory sinus arrhythmia (RSA) corresponding to modulation of the instantaneous cardiac frequency by the rhythm of respiration. HRV has been intensively studied using traditional spectral analyses, e.g. by Fourier transform or autoregressive methods, and, because of its complexity, has been used as a paradigm for testing several proposed new methods of complexity analysis. These methods are reviewed. The application of time-frequency methods to HRV is considered, including in particular the wavelet transform which can resolve the time-dependent spectral content of HRV. Attention is focused on the cardio-respiratory interaction by introduction of the respiratory frequency variability signal (RFV), which can be acquired simultaneously with HRV by use of a respiratory effort transducer. Current methods for the analysis of interacting oscillators are reviewed and applied to cardio-respiratory data, including those for the quantification of synchronization and direction of coupling. These reveal the effect of ageing on the cardio-respiratory interaction through changes in the mutual modulation of the instantaneous cardiac and respiratory frequencies. Analyses of blood flow signals recorded with laser Doppler flowmetry are reviewed and related to the current understanding of how endothelial-dependent oscillations evolve with age: the inner lining of the vessels (the endothelium) is shown to be of crucial importance to the emerging picture. It is concluded that analyses of the complex and nonlinear dynamics of the cardiovascular system can illuminate the mechanisms of blood circulation, and that the heart, the lungs and the vascular system function as a single entity in dynamical terms. Clear evidence is found for dynamical ageing.

21 CFR 522.820 - Erythromycin.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...

21 CFR 522.820 - Erythromycin.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...

21 CFR 522.820 - Erythromycin.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...

21 CFR 522.820 - Erythromycin.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...

21 CFR 522.820 - Erythromycin.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Indications for use. For the treatment of bacterial pneumonia, upper respiratory infections (tonsillitis... for use. For the treatment of bacterial pneumonia, upper respiratory infections (rhinitis, bronchitis... disease (shipping fever complex and bacterial pneumonia) associated with Pasteurella multocida susceptible...

Caveolae provide a specialized membrane environment for respiratory syncytial virus assembly

PubMed Central

Nguyen, Tra Huong; Leong, Daniel; Ravi, Laxmi Iyer; Tan, Boon Huan; Sandin, Sara; Sugrue, Richard J.

2017-01-01

ABSTRACT Respiratory syncytial virus (RSV) is an enveloped virus that assembles into filamentous virus particles on the surface of infected cells. Morphogenesis of RSV is dependent upon cholesterol-rich (lipid raft) membrane microdomains, but the specific role of individual raft molecules in RSV assembly is not well defined. Here, we show that RSV morphogenesis occurs within caveolar membranes and that both caveolin-1 and cavin-1 (also known as PTRF), the two major structural and functional components of caveolae, are actively recruited to and incorporated into the RSV envelope. The recruitment of caveolae occurred just prior to the initiation of RSV filament assembly, and was dependent upon an intact actin network as well as a direct physical interaction between caveolin-1 and the viral G protein. Moreover, cavin-1 protein levels were significantly increased in RSV-infected cells, leading to a virus-induced change in the stoichiometry and biophysical properties of the caveolar coat complex. Our data indicate that RSV exploits caveolae for its assembly, and we propose that the incorporation of caveolae into the virus contributes to defining the biological properties of the RSV envelope. PMID:28154158

Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity.

PubMed

Thomas, David C; Clare, Simon; Sowerby, John M; Pardo, Mercedes; Juss, Jatinder K; Goulding, David A; van der Weyden, Louise; Storisteanu, Daniel; Prakash, Ananth; Espéli, Marion; Flint, Shaun; Lee, James C; Hoenderdos, Kim; Kane, Leanne; Harcourt, Katherine; Mukhopadhyay, Subhankar; Umrania, Yagnesh; Antrobus, Robin; Nathan, James A; Adams, David J; Bateman, Alex; Choudhary, Jyoti S; Lyons, Paul A; Condliffe, Alison M; Chilvers, Edwin R; Dougan, Gordon; Smith, Kenneth G C

2017-04-03

The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91 phox and p22 phox subunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse gene bc017643 , and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91 phox and p22 phox Consequently, Eros -deficient mice quickly succumb to infection. Eros also contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases. Eros is an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense. © 2017 Thomas et al.

Mitochondrial Dysfunction in Schizophrenia: Determination of Mitochondrial Respiratory Activity in a Two-Hit Mouse Model.

PubMed

Monpays, Cécile; Deslauriers, Jessica; Sarret, Philippe; Grignon, Sylvain

2016-08-01

Schizophrenia is a chronic mental illness in which mitochondrial dysfunction has been suggested. Our laboratory recently developed a juvenile murine two-hit model (THM) of schizophrenia based on the combination of gestational inflammation, followed by juvenile restraint stress. We previously reported that relevant behaviors and neurochemical disturbances, including oxidative stress, were reversed by the antioxidant lipoic acid (LA), thereby pointing to the central role played by oxidative abnormalities and prompting us to investigate mitochondrial function. Mitochondrial activity was determined with the MitoXpress® commercial kit in two schizophrenia-relevant regions (prefrontal cortex (PFC) and striatum). Measurements were performed in state 3, with substrates for complex I- and complex II-induced respiratory activity (IRA). We observed an increase in complex I IRA in the PFC and striatum in both sexes but an increase in complex II activity only in males. LA treatment prevented this increase only in complex II IRA in males. Expression levels of the different respiratory chain complexes, as well as fission/fusion proteins and protein carbonylation, were unchanged. In conclusion, our juvenile schizophrenia THM shows an increase in mitochondrial activity reversed by LA, specifically in complex II IRA in males. Further investigations are required to determine the mechanisms of these modifications.

Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene.

PubMed

Martín, Miguel A; Blázquez, Alberto; Gutierrez-Solana, Luis G; Fernández-Moreira, Daniel; Briones, Paz; Andreu, Antoni L; Garesse, Rafael; Campos, Yolanda; Arenas, Joaquín

2005-04-01

Mutations in the nuclear-encoded subunits of complex I of the mitochondrial respiratory chain are a recognized cause of Leigh syndrome (LS). Recently, 6 mutations in the NDUFS1 gene were identified in 3 families. To describe a Spanish family with LS, complex I deficiency in muscle, and a novel mutation in the NDUFS1 gene. Using molecular genetic approaches, we identified the underlying molecular defect in a patient with LS with a complex I defect. The proband was a child who displayed the clinical features of LS. Muscle biochemistry results showed a complex I defect of the mitochondrial respiratory chain. Sequencing analysis of the mitochondrial DNA-encoded ND genes, the nuclear DNA-encoded NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS6, NDUFS7, NDUFS8, and NDUFAB1 genes, and the complex I assembly factor CIA30 gene revealed a novel homozygous L231V mutation (c.691C-->G) in the NDUFS1 gene. The parents were heterozygous carriers of the L231V mutation. Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.

Mitochondrial hepato-encephalopathy due to deficiency of QIL1/MIC13 (C19orf70), a MICOS complex subunit.

PubMed

Zeharia, Avraham; Friedman, Jonathan R; Tobar, Ana; Saada, Ann; Konen, Osnat; Fellig, Yacov; Shaag, Avraham; Nunnari, Jodi; Elpeleg, Orly

2016-12-01

The mitochondrial inner membrane possesses distinct subdomains including cristae, which are lamellar structures invaginated into the mitochondrial matrix and contain the respiratory complexes. Generation of inner membrane domains requires the complex interplay between the respiratory complexes, mitochondrial lipids and the recently identified mitochondrial contact site and cristae organizing system (MICOS) complex. Proper organization of the mitochondrial inner membrane has recently been shown to be important for respiratory function in yeast. Here we aimed at a molecular diagnosis in a brother and sister from a consanguineous family who presented with a neurodegenerative disorder accompanied by hyperlactatemia, 3-methylglutaconic aciduria, disturbed hepatocellular function with abnormal cristae morphology in liver and cerebellar and vermis atrophy, which suggest mitochondrial dysfunction. Using homozygosity mapping and exome sequencing the patients were found to be homozygous for the p.(Gly15Glufs*75) variant in the QIL1/MIC13 (C19orf70) gene. QIL1/MIC13 is a constituent of MICOS, a six subunit complex that helps to form and/or stabilize cristae junctions and determine the placement, distribution and number of cristae within mitochondria. In patient fibroblasts both MICOS subunits QIL1/MIC13 and MIC10 were absent whereas MIC60 was present in a comparable abundance to that of the control. We conclude that QIL1/MIC13 deficiency in human, is associated with disassembly of the MICOS complex, with the associated aberration of cristae morphology and mitochondrial respiratory dysfunction. 3-Methylglutaconic aciduria is associated with variants in genes encoding mitochondrial inner membrane organizing determinants, including TAZ, DNAJC19, SERAC1 and QIL1/MIC13.

Respiratory hospitalizations in association with fine PM and its components in New York State

EPA Science Inventory

Despite observed geographic and temporal variation in particulate matter (PM)-related health morbidities, only a small number of epidemiologic studies have evaluated the relation between PM2.5 chemical constituents and respiratory disease. Most assessments are limited by inadequa...

Immunopathogenesis of Staphylococcus aureus pulmonary infection

PubMed Central

Parker, Dane; Prince, Alice

2013-01-01

Staphylococcus aureus is a common human pathogen highly evolved as both a component of the commensal flora and as a major cause of invasive infection. Severe respiratory infection due to staphylococci has been increasing due to the prevalence of more virulent USA300 CA-MRSA strains in the general population. The ability of S. aureus to adapt to the milieu of the respiratory tract has facilitated its emergence as a respiratory pathogen. Its metabolic versatility, the ability to scavenge iron, coordinate gene expression, and the horizontal acquisition of useful genetic elements have all contributed to its success as a component of the respiratory flora, in hospitalized patients, as a complication of influenza and in normal hosts. The expression of surface adhesins facilitates its persistence in the airways. In addition, the highly sophisticated interactions of the multiple S. aureus virulence factors, particularly the α-hemolysin and protein A, with diverse immune effectors in the lung such as ADAM10, TNFR1, EGFR, immunoglobulin, and complement all contribute to the pathogenesis of staphylococcal pneumonia. PMID:22037948

Evidence-based effectiveness of vaccination against Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in feedlot cattle for mitigating the incidence and effect of bovine respiratory disease complex.

PubMed

Larson, R L; Step, D L

2012-03-01

Bovine respiratory disease complex is the leading cause of morbidity and mortality in feedlot cattle. A number of vaccines against bacterial respiratory pathogens are commercially available and researchers have studied their impact on morbidity, mortality, and other disease outcome measures in feedlot cattle. A systematic review will provide veterinarians with a rigorous and transparent evaluation of the published literature to estimate the extent of vaccine effect. Unfortunately, the published body of evidence does not provide a consistent estimate of the direction and magnitude of effectiveness in feedlot cattle vaccination against Mannheimia haemolytica, Pasteurella multocida, or Histophilus somni.

[The changes of physiological reactivity of cardiorespiratory system to respiratory homeostasis with the use of complex stimulation of special work capacity].

PubMed

Lysenko, O M

2012-01-01

We present the influence of the program of special additional stimulation of work capacity of high-performance athletes on the sensitivity of cardiorespiratory system to hypercapnic and hypoxic shifts in respiratory homeostasis. We found that under the influence of the pre-start complex a decrease in the sensitivity of ventilator responses to CO2-H+ stimuli in combination with a reduction in the thresholds of the reaction take place. This creates conditions for increased mobilization properties of the cardiorespiratory system and economization of its reaction under conditions of changes of respiratory homeostasis characteristic of intense training and competitive loads in the sport.

Performance characteristics of the new Abbott Real Time MTB assay for detection of Mycobacterium tuberculosis complex in respiratory specimens.

PubMed

Vinuesa, Víctor; Navarro, David; Poujois, Sandrine; Zaragoza, Susana; Borrás, Rafael

2016-03-01

The performance of the Abbott Real Time MTB assay for detection of Mycobacterium tuberculosis complex in respiratory specimens was evaluated using a standard culture as the reference. The overall concordance between both methods was 0.95. The assay displayed an excellent sensitivity (100% for smear-positive/92.3% for smear-negative specimens) and specificity (100%). Copyright © 2015 Elsevier Inc. All rights reserved.

Comparative analysis of respiratory chain and oxidative phosphorylation in Leishmania tarentolae, Crithidia fasciculata, Phytomonas serpens and procyclic stage of Trypanosoma brucei.

PubMed

Verner, Zdeněk; Cermáková, Petra; Skodová, Ingrid; Kováčová, Bianka; Lukeš, Julius; Horváth, Anton

2014-01-01

Trypanosomatids are unicellular parasites living in a wide range of host environments, which to large extent shaped their mitochondrial energy metabolism, resulting in quite large differences even among closely related flagellates. In a comparative manner, we analyzed the activities and composition of mitochondrial respiratory complexes in four species (Leishmania tarentolae, Crithidia fasciculata, Phytomonas serpens and Trypanosoma brucei), which represent the main model trypanosomatids. Moreover, we measured the activity of mitochondrial glycerol-3-phosphate dehydrogenase, the overall oxygen consumption and the mitochondrial membrane potential in each species. The comparative analysis suggests an inverse relationship between the activities of respiratory complexes I and II, as well as the overall activity of the canonical complexes and glycerol-3-phosphate dehydrogenase. Our comparative analysis shows that mitochondrial functions are highly variable in these versatile parasites. Copyright © 2014 Elsevier B.V. All rights reserved.

Azoxystrobin, a mitochondrial complex III Qo site inhibitor, exerts beneficial metabolic effects in vivo and in vitro.

PubMed

Gao, An-Hui; Fu, Yan-Yun; Zhang, Kun-Zhi; Zhang, Mei; Jiang, Hao-Wen; Fan, Li-Xia; Nan, Fa-Jun; Yuan, Chong-Gang; Li, Jia; Zhou, Yu-Bo; Li, Jing-Ya

2014-07-01

Several anti-diabetes drugs exert beneficial effects against metabolic syndrome by inhibiting mitochondrial function. Although much progress has been made toward understanding the role of mitochondrial function inhibitors in treating metabolic diseases, the potential effects of these inhibitors on mitochondrial respiratory chain complex III remain unclear. We investigated the metabolic effects of azoxystrobin (AZOX), a Qo inhibitor of complex III, in a high-fat diet-fed mouse model with insulin resistance in order to elucidate the mechanism by which AZOX improves glucose and lipid metabolism at the metabolic cellular level. Acute administration of AZOX in mice increased the respiratory exchange ratio. Chronic treatment with AZOX reduced body weight and significantly improved glucose tolerance and insulin sensitivity in high-fat diet-fed mice. AZOX treatment resulted in decreased triacylglycerol accumulation and down-regulated the expression of genes involved in liver lipogenesis. AZOX increased glucose uptake in L6 myotubes and 3T3-L1 adipocytes and inhibited de novo lipogenesis in HepG2 cells. The findings indicate that AZOX-mediated alterations to lipid and glucose metabolism may depend on AMP-activated protein kinase (AMPK) signaling. AZOX, a Qo inhibitor of mitochondrial respiratory complex III, exerts whole-body beneficial effects on the regulation of glucose and lipid homeostasis in high-fat diet-fed mice. These findings provide evidence that a Qo inhibitor of mitochondrial respiratory complex III could represent a novel approach for the treatment of obesity. Copyright © 2014 Elsevier B.V. All rights reserved.

Analysis of the respiratory component of heart rate variability in the Cururu toad Rhinella schneideri.

PubMed

Zena, Lucas A; Leite, Cléo A C; Longhini, Leonardo S; Dias, Daniel P M; da Silva, Glauber S F; Hartzler, Lynn K; Gargaglioni, Luciane H; Bícego, Kênia C

2017-11-23

Beat-to-beat variation in heart rate (f H ) has been used as a tool for elucidating the balance between sympathetic and parasympathetic modulation of the heart. A portion of the temporal changes in f H is evidenced by a respiratory influence (cardiorespiratory interaction) on heart rate variability (HRV) with heartbeats increasing and decreasing within a respiratory cycle. Nevertheless, little is known about respiratory effects on HRV in lower vertebrates. By using frequency domain analysis, we provide the first evidence of a ventilatory component in HRV similar to mammalian respiratory sinus arrhythmia in an amphibian, the toad Rhinella schneideri. Increases in the heartbeats arose synchronously with each lung inflation cycle, an intermittent breathing pattern comprised of a series of successive lung inflations. A well-marked peak in the HRV signal matching lung inflation cycle was verified in toads whenever lung inflation cycles exhibit a regular rhythm. The cardiac beat-to-beat variation evoked at the moment of lung inflation accounts for both vagal and sympathetic influences. This cardiorespiratory interaction may arise from interactions between central and peripheral feedback mechanisms governing cardiorespiratory control and may underlie important cardiorespiratory adjustments for gas exchange improvement especially under extreme conditions like low oxygen availability.

Respiratory hospitalizations in association with fine PM and its ...

EPA Pesticide Factsheets

Despite observed geographic and temporal variation in particulate matter (PM)-related health morbidities, only a small number of epidemiologic studies have evaluated the relation between PM2.5 chemical constituents and respiratory disease. Most assessments are limited by inadequate spatial and temporal resolution of ambient PM measurements and/or by their approaches to examine the role of specific PM components on health outcomes. In a case-crossover analysis using daily average ambient PM2.5 total mass and species estimates derived from the Community Multiscale Air Quality (CMAQ) model and available observations, we examined the association between the chemical components of PM (including elemental and organic carbon, sulfate, nitrate, ammonium, and other remaining) and respiratory hospitalizations in New York State. We evaluated relationships between levels (low, medium, high) of PM constituent mass fractions, and assessed modification of the PM2.5–hospitalization association via models stratified by mass fractions of both primary and secondary PM components. In our results, average daily PM2.5 concentrations in New York State were generally lower than the 24-hr average National Ambient Air Quality Standard (NAAQS). Year-round analyses showed statistically significant positive associations between respiratory hospitalizations and PM2.5 total mass, sulfate, nitrate, and ammonium concentrations at multiple exposure lags (0.5–2.0% per interquartile range [IQR

Laser ablation of Dbx1 neurons in the pre-Bötzinger complex stops inspiratory rhythm and impairs output in neonatal mice

PubMed Central

Wang, Xueying; Hayes, John A; Revill, Ann L; Song, Hanbing; Kottick, Andrew; Vann, Nikolas C; LaMar, M Drew; Picardo, Maria Cristina D; Akins, Victoria T; Funk, Gregory D; Del Negro, Christopher A

2014-01-01

To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality. Breathing-related interneurons of the brainstem pre-Bötzinger complex (preBötC) that putatively comprise the core respiratory rhythm generator in mammals are derived from Dbx1-expressing precursors. Here, we show that selective photonic destruction of Dbx1 preBötC neurons in neonatal mouse slices impairs respiratory rhythm but surprisingly also the magnitude of motor output; respiratory hypoglossal nerve discharge decreased and its frequency steadily diminished until rhythm stopped irreversibly after 85±20 (mean ± SEM) cellular ablations, which corresponds to ∼15% of the estimated population. These results demonstrate that a single canonical interneuron class generates respiratory rhythm and contributes in a premotor capacity, whereas these functions are normally attributed to discrete populations. We also establish quantitative cellular parameters that govern network viability, which may have ramifications for respiratory pathology in disease states. DOI: http://dx.doi.org/10.7554/eLife.03427.001 PMID:25027440

[Respiratory monitoring of pediatric patients in the Intensive Care Unit].

PubMed

Donoso, Alejandro; Arriagada, Daniela; Contreras, Dina; Ulloa, Daniela; Neumann, Megan

Respiratory monitoring plays an important role in the care of children with acute respiratory failure. Therefore, its proper use and correct interpretation (recognizing which signals and variables should be prioritized) should help to a better understanding of the pathophysiology of the disease and the effects of therapeutic interventions. In addition, ventilated patient monitoring, among other determinations, allows to evaluate various parameters of respiratory mechanics, know the status of the different components of the respiratory system and guide the adjustments of ventilatory therapy. In this update, the usefulness of several techniques of respiratory monitoring including conventional respiratory monitoring and more recent methods are described. Moreover, basic concepts of mechanical ventilation, their interpretation and how the appropriate analysis of the information obtained can cause an impact on the clinical management of the patient are defined. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

Approximate entropy of human respiratory movement during eye-closed waking and different sleep stages.

PubMed

Burioka, Naoto; Cornélissen, Germaine; Halberg, Franz; Kaplan, Daniel T; Suyama, Hisashi; Sako, Takanori; Shimizu, Eiji

2003-01-01

The breath-to-breath variability of respiratory parameters changes with sleep stage. This study investigates any alteration in the approximate entropy (ApEn) of respiratory movement as a gauge of complexity in respiration, by stage of consciousness, in the light of putative brain interactions. Eight healthy men, who were between the ages of 23 and 29 years, were investigated. The signals of chest wall movement and EEG were recorded from 10:30 PM to 6:00 AM. After analog-to-digital conversion, the ApEn of respiratory movement (3 min) and EEG (20 s) were computed. Surrogate data were tested for nonlinearity in the original time series. The most impressive reduction in the ApEn of respiratory movement was associated with stage IV sleep, when the ApEn of the EEG was also statistically significantly decreased. A statistically significant linear relation is found between the ApEn of both variables. Surrogate data indicated that respiratory movement had nonlinear properties during all stages of consciousness that were investigated. Respiratory movement and EEG signals are more regular during stage IV sleep than during other stages of consciousness. The change in complexity described by the ApEn of respiration depends in part on the ApEn of the EEG, suggesting the involvement of nonlinear dynamic processes in the coordination between brain and lungs.

Dembo polymerase chain reaction technique for detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs.

PubMed

Rahpaya, Sayed Samim; Tsuchiaka, Shinobu; Kishimoto, Mai; Oba, Mami; Katayama, Yukie; Nunomura, Yuka; Kokawa, Saki; Kimura, Takashi; Kobayashi, Atsushi; Kirino, Yumi; Okabayashi, Tamaki; Nonaka, Nariaki; Mekata, Hirohisa; Aoki, Hiroshi; Shiokawa, Mai; Umetsu, Moeko; Morita, Tatsushi; Hasebe, Ayako; Otsu, Keiko; Asai, Tetsuo; Yamaguchi, Tomohiro; Makino, Shinji; Murata, Yoshiteru; Abi, Ahmad Jan; Omatsu, Tsutomu; Mizutani, Tetsuya

2018-05-31

Bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds, and rodents. However, experimental data supporting this possibility are scarce. We collected 117 samples and screened them for 44 bovine abortive, diarrheal, and respiratory disease complex pathogens by using Dembo polymerase chain reaction (PCR), which is based on TaqMan real-time PCR. Fifty-seven samples were positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, Salmonella enterica ser. Typhimurium, and Neospora caninum ; some samples were positive for multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus were the most frequently detected pathogens, especially in flies, suggesting an important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggest that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of abortion, diarrhea, and respiratory infectious agents, and that they may transmit more than one pathogen at the same time.

Expression profiles of genes for mitochondrial respiratory energy-dissipating systems and antioxidant enzymes in wheat leaves during de-etiolation.

PubMed

Garmash, Elena V; Velegzhaninov, Ilya O; Grabelnych, Olga I; Borovik, Olga A; Silina, Ekaterina V; Voinikov, Victor K; Golovko, Tamara K

2017-08-01

Mitochondrial respiratory components participate in the maintenance of chloroplast functional activity. This study investigates the effects 48h de-etiolation of spring wheat seedlings (Triticum aestivum L., var. Irgina) on the expression of genes that encode energy-dissipating respiratory components and antioxidant enzymes under continuous light conditions. The expression of AOX1a following the prolonged darkness exhibited a pattern indicating a prominent dependence on light. The expression of other respiratory genes, including NDA2, NDB2, and UCP1b, increased during de-etiolation and dark-to-light transition; however, changes in the expression of these genes occurred later than those in AOX1a expression. A high expression of NDA1 was detected after 12h of de-etiolation. The suppression of AOX1a, NDA2, NDB2, and UCP1b was observed 24h after de-etiolation when the photosynthetic apparatus and its defence systems against excess light were completely developed. The expression patterns of the respiratory genes and several genes encoding antioxidant enzymes (MnSOD, Cu-ZnSOD, t-APX, GR, and GRX) were quite similar. Our data indicate that the induction of nuclear genes encoding respiratory and antioxidant enzymes allow the plants to control reactive oxygen species (ROS) production and avoid oxidative stress during de-etiolation. Copyright © 2017 Elsevier GmbH. All rights reserved.

The translational landscape of Arabidopsis mitochondria.

PubMed

Planchard, Noelya; Bertin, Pierre; Quadrado, Martine; Dargel-Graffin, Céline; Hatin, Isabelle; Namy, Olivier; Mireau, Hakim

2018-06-05

Messenger RNA translation is a complex process that is still poorly understood in eukaryotic organelles like mitochondria. Growing evidence indicates though that mitochondrial translation differs from its bacterial counterpart in many key aspects. In this analysis, we have used ribosome profiling technology to generate a genome-wide snapshot view of mitochondrial translation in Arabidopsis. We show that, unlike in humans, most Arabidopsis mitochondrial ribosome footprints measure 27 and 28 bases. We also reveal that respiratory subunits encoding mRNAs show much higher ribosome association than other mitochondrial mRNAs, implying that they are translated at higher levels. Homogenous ribosome densities were generally detected within each respiratory complex except for complex V, where higher ribosome coverage corroborated with higher requirements for specific subunits. In complex I respiratory mutants, a reorganization of mitochondrial mRNAs ribosome association was detected involving increased ribosome densities for certain ribosomal protein encoding transcripts and a reduction in translation of a few complex V mRNAs. Taken together, our observations reveal that plant mitochondrial translation is a dynamic process and that translational control is important for gene expression in plant mitochondria. This study paves the way for future advances in the understanding translation in higher plant mitochondria.

Chronic exposure to nitric oxide alters the free iron pool in endothelial cells: Role of mitochondrial respiratory complexes and heat shock proteins

PubMed Central

Ramachandran, Anup; Ceaser, Erin; Darley-Usmar, Victor M.

2004-01-01

The mechanisms of nitric oxide (NO) signaling include binding to the iron centers in soluble guanylate cyclase and cytochrome c oxidase and posttranslational modification of proteins by S-nitrosation. Low levels of NO control mitochondrial number in cells, but little is known of the impact of chronic exposure to high levels of NO on mitochondrial function in endothelial cells. The focus of this study is the interaction of NO with mitochondrial respiratory complexes in cell culture and the effect this has on iron homeostasis. We demonstrate that chronic exposure of endothelial cells to NO decreased activity and protein levels of complexes I, II, and IV, whereas citrate synthase and ATP synthase were unaffected. Inhibition of these respiratory complexes was accompanied by an increase in cellular S-nitrosothiol levels, modification of cysteines residues, and an increase in the labile iron pool. The NO-dependent increase in the free iron pool and inhibition of complex II was prevented by inhibition of mitochondrial protein synthesis, consistent with a major contribution of the organelle to iron homeostasis. In addition, inhibition of mitochondrial protein synthesis was associated with an increase in heat shock protein 60 levels, which may be an additional mechanism leading to preservation of complex II activity. PMID:14691259

Tributyltin (TBT) and mitochondrial respiration in mussel digestive gland.

PubMed

Nesci, Salvatore; Ventrella, Vittoria; Trombetti, Fabiana; Pirini, Maurizio; Pagliarani, Alessandra

2011-06-01

The toxicity of organotins and especially tri-n-butyltin (TBT) on mitochondria is well known. However as far as we are aware, effects on mitochondrial respiration are unexplored in mollusks. In this work mitochondria isolated from the digestive gland of Mytilus galloprovincialis and susceptive to the classical respiratory chain inhibitors, were assayed in the presence of micromolar TBT concentrations to investigate mitochondrial respiratory activities. Intact and freeze-thawed mitochondria were used. TBT significantly inhibited oxygen consumption in the presence of glutamate/malate or succinate as substrates. Conversely cytochrome c oxidase activity (complex IV), assayed both polarographically and spectrophotometrically, was unaffected. The addition of 1,4-dithioerythritol (DTE) decreased the TBT-driven inhibition of complexes I and III. The TBT capability of covalent binding to thiol groups of mitochondrial proteins in a dose-dependent manner was confirmed by the aid of Ellman's reagent. Data strongly suggests that TBT may prevent the electron transfer from complexes I and III to downhill respiratory chain complexes by binding to critical SH residues. Copyright © 2011 Elsevier Ltd. All rights reserved.

21 CFR 520.2261b - Sulfamethazine powder.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and bovine respiratory disease complex (shipping fever complex) (Pasteurella spp.), colibacillosis... (F. necrophorum), acute mastitis (Streptococcus spp.), and acute metritis (Streptococcus spp.) (iii...

The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle.

PubMed

Brautbar, Ariel; Wang, Jing; Abdenur, Jose E; Chang, Richard C; Thomas, Janet A; Grebe, Theresa A; Lim, Cynthia; Weng, Shao-Wen; Graham, Brett H; Wong, Lee-Jun

2008-08-01

The mitochondrial 13513G>A (D393N) mutation in the ND5 subunit of the respiratory chain complex I was initially described in association with MELAS syndrome. Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disease. The mutation was found in a total of 5 patients. An additional patient who had clinical presentation consistent with a Leigh-like phenotype but with a normal brain MRI was added to the cohort. None of an additional 88 patients meeting MELAS disease criteria, nor 56 patients with respiratory chain deficiency screened for the 13513G>A were found positive for the mutation. The most frequent clinical manifestations in our patients were hypotonia, ocular and cerebellar involvement. Low mutation heteroplasmy in the range of 20-40% was observed in all 6 patients. This observation is consistent with the previously reported low heteroplasmy of this mutation in some patients with the 13513G>A mutation and complex I deficiency. However, normal complex I activity was observed in two patients in our cohort. As most patients with Leigh-like disease and the 13513G>A mutation have been described with complex I deficiency, this report adds to the previously reported subset of patients with normal respiratory complex function. We conclude that in any patient with Leigh or Leigh-like disease, testing for the 13513G>A mutation is clinically relevant and low mutant loads in blood or muscle may be considered pathogenic, in the presence of normal respiratory chain enzyme activities.

Translation and Assembly of Radiolabeled Mitochondrial DNA-Encoded Protein Subunits from Cultured Cells and Isolated Mitochondria.

PubMed

Formosa, Luke E; Hofer, Annette; Tischner, Christin; Wenz, Tina; Ryan, Michael T

2016-01-01

In higher eukaryotes, the mitochondrial electron transport chain consists of five multi-subunit membrane complexes responsible for the generation of cellular ATP. Of these, four complexes are under dual genetic control as they contain subunits encoded by both the mitochondrial and nuclear genomes, thereby adding another layer of complexity to the puzzle of respiratory complex biogenesis. These subunits must be synthesized and assembled in a coordinated manner in order to ensure correct biogenesis of different respiratory complexes. Here, we describe techniques to (1) specifically radiolabel proteins encoded by mtDNA to monitor the rate of synthesis using pulse labeling methods, and (2) analyze the stability, assembly, and turnover of subunits using pulse-chase methods in cultured cells and isolated mitochondria.

Respiratory syncytial virus infection in cattle.

PubMed

Sacco, R E; McGill, J L; Pillatzki, A E; Palmer, M V; Ackermann, M R

2014-03-01

Bovine respiratory syncytial virus (RSV) is a cause of respiratory disease in cattle worldwide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV infection can predispose calves to secondary bacterial infection by organisms such as Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, resulting in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Even in cases where animals do not succumb to bovine respiratory disease complex, there can be long-term losses in production performance. This includes reductions in feed efficiency and rate of gain in the feedlot, as well as reproductive performance, milk production, and longevity in the breeding herd. As a result, economic costs to the cattle industry from bovine respiratory disease have been estimated to approach $1 billion annually due to death losses, reduced performance, and costs of vaccinations and treatment modalities. Human and bovine RSV are closely related viruses with similarities in histopathologic lesions and mechanisms of immune modulation induced following infection. Therefore, where appropriate, we provide comparisons between RSV infections in humans and cattle. This review article discusses key aspects of RSV infection of cattle, including epidemiology and strain variability, clinical signs and diagnosis, experimental infection, gross and microscopic lesions, innate and adaptive immune responses, and vaccination strategies.

Analyzing non-respiratory movements of the chest: methods and devices

NASA Astrophysics Data System (ADS)

Pariaszewska, Katarzyna; Młyńczak, Marcel; Cybulski, Gerard

2015-09-01

Respiration is the main reason of the chest movements. However, there are also non-respiratory ones, resulting from e.g. snoring, wheezing, stridor, throat clearing or coughing. They may exist sporadically, however should be examined in case when their incidences increase. Detecting non-respiratory movements is very important, because many of them are symptoms of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) or lung cancer. Assessment of the presence of non-respiratory movements could be important element of effective diagnosis. It is also necessary to provide quantitative and objective results for intra-subject studies. Most of these events generate vibroacoustic signals that contain components of sound and vibrations. This work provides the review of the solutions and devices for monitoring of the non-respiratory movements, primarily considering the accuracy of the chest movements' detection and distinguishing.

Raphé neurons stimulate respiratory circuit activity by multiple mechanisms via endogenously released serotonin and substance P

PubMed Central

Ptak, Krzysztof; Yamanishi, Tadashi; Aungst, Jason; Milescu, Lorin S.; Zhang, Ruli; Richerson, George B.; Smith, Jeffrey C.

2010-01-01

Brainstem serotonin (5-HT) neurons modulate activity of many neural circuits in the mammalian brain, but in many cases endogenous mechanisms have not been resolved. Here, we analyzed actions of raphé 5-HT neurons on respiratory network activity including at the level of the pre–Bötzinger complex (pre-BötC) in neonatal rat medullary slices in vitro, and in the more intact nervous system of juvenile rats in arterially perfused brainstem-spinal cord preparations in situ. At basal levels of activity, excitation of the respiratory network via simultaneous release of 5-HT and substance P (SP), acting at 5-HT2A/2C, 5-HT4 and/or neurokinin-1 receptors, was required to maintain inspiratory motor output in both the neonatal and juvenile systems. The midline raphé obscurus contained spontaneously active 5-HT neurons, some of which projected to the pre-BötC and hypoglossal motoneurons, co-localized 5-HT and SP, and received reciprocal excitatory connections from the pre-BötC. Experimentally augmenting raphé obscurus activity increased motor output by simultaneously exciting pre-BötC and motor neurons. Biophysical analyses in vitro demonstrated that 5-HT and SP modulated background cation conductances in pre-BötC and motor neurons, including a non–selective cation leak current that contributed to the resting potential, which explains the neuronal depolarization that augmented motor output. Furthermore, we found that 5-HT, but not SP, can transform the electrophysiological phenotype of some pre-BötC neurons to intrinsic bursters, providing 5-HT with an additional role in promoting rhythm generation. We conclude that raphé 5-HT neurons excite key circuit components required for generation of respiratory motor output. PMID:19321769

The preBötzinger complex as a hub for network activity along the ventral respiratory column in the neonate rat.

PubMed

Gourévitch, Boris; Mellen, Nicholas

2014-09-01

In vertebrates, respiratory control is ascribed to heterogeneous respiration-modulated neurons along the Ventral Respiratory Column (VRC) in medulla, which includes the preBötzinger Complex (preBötC), the putative respiratory rhythm generator. Here, the functional anatomy of the VRC was characterized via optical recordings in the sagittaly sectioned neonate rat hindbrain, at sampling rates permitting coupling estimation between neuron pairs, so that each neuron was described using unitary, neuron-system, and coupling attributes. Structured coupling relations in local networks, significantly oriented coupling in the peri-inspiratory interval detected in pooled data, and significant correlations between firing rate and expiratory duration in subsets of neurons revealed network regulation at multiple timescales. Spatially averaged neuronal attributes, including coupling vectors, revealed a sharp boundary at the rostral margin of the preBötC, as well as other functional anatomical features congruent with identified structures, including the parafacial respiratory group and the nucleus ambiguus. Cluster analysis of attributes identified two spatially compact, homogenous groups: the first overlapped with the preBötC, and was characterized by strong respiratory modulation and dense bidirectional coupling with itself and other groups, consistent with a central role for the preBötC in respiratory control; the second lay between preBötC and the facial nucleus, and was characterized by weak respiratory modulation and weak coupling with other respiratory neurons, which is congruent with cardiovascular regulatory networks that are found in this region. Other groups identified using cluster analysis suggested that networks along VRC regulated expiratory duration, and the transition to and from inspiration, but these groups were heterogeneous and anatomically dispersed. Thus, by recording local networks in parallel, this study found evidence for respiratory regulation at multiple timescales along the VRC, as well as a role for the preBötC in the integration of functionally disparate respiratory neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

Transcriptomic dissection reveals wide spread differential expression in chickpea during early time points of Fusarium oxysporum f. sp. ciceri Race 1 attack

PubMed Central

Ghosh, Amartya

2017-01-01

Plants’ reaction to underground microorganisms is complex as sessile nature of plants compels them to prioritize their responses to diverse microorganisms both pathogenic and symbiotic. Roots of important crops are directly exposed to diverse microorganisms, but investigations involving root pathogens are significantly less. Thus, more studies involving root pathogens and their target crops are necessitated to enrich the understanding of underground interactions. Present study reported the molecular complexities in chickpea during Fusarium oxysporum f. sp. ciceri Race 1 (Foc1) infection. Transcriptomic dissections using RNA-seq showed significantly differential expression of molecular transcripts between infected and control plants of both susceptible and resistant genotypes. Radar plot analyses showed maximum expressional undulations after infection in both susceptible and resistant plants. Gene ontology and functional clustering showed large number of transcripts controlling basic metabolism of plants. Network analyses demonstrated defense components like peptidyl cis/trans isomerase, MAP kinase, beta 1,3 glucanase, serine threonine kinase, patatin like protein, lactolylglutathione lyase, coproporphyrinogen III oxidase, sulfotransferases; reactive oxygen species regulating components like respiratory burst oxidase, superoxide dismutases, cytochrome b5 reductase, glutathione reductase, thioredoxin reductase, ATPase; metabolism regulating components, myo inositol phosphate, carboxylate synthase; transport related gamma tonoplast intrinsic protein, and structural component, ubiquitins to serve as important nodals of defense signaling network. These nodal molecules probably served as hub controllers of defense signaling. Functional characterization of these hub molecules would not only help in developing better understanding of chickpea-Foc1 interaction but also place them as promising candidates for resistance management programs against vascular wilt of legumes. PMID:28542579

Characterization of the pharmacokinetics of gasoline using PBPK modeling with a complex mixtures chemical lumping approach.

PubMed

Dennison, James E; Andersen, Melvin E; Yang, Raymond S H

2003-09-01

Gasoline consists of a few toxicologically significant components and a large number of other hydrocarbons in a complex mixture. By using an integrated, physiologically based pharmacokinetic (PBPK) modeling and lumping approach, we have developed a method for characterizing the pharmacokinetics (PKs) of gasoline in rats. The PBPK model tracks selected target components (benzene, toluene, ethylbenzene, o-xylene [BTEX], and n-hexane) and a lumped chemical group representing all nontarget components, with competitive metabolic inhibition between all target compounds and the lumped chemical. PK data was acquired by performing gas uptake PK studies with male F344 rats in a closed chamber. Chamber air samples were analyzed every 10-20 min by gas chromatography/flame ionization detection and all nontarget chemicals were co-integrated. A four-compartment PBPK model with metabolic interactions was constructed using the BTEX, n-hexane, and lumped chemical data. Target chemical kinetic parameters were refined by studies with either the single chemical alone or with all five chemicals together. o-Xylene, at high concentrations, decreased alveolar ventilation, consistent with respiratory irritation. A six-chemical interaction model with the lumped chemical group was used to estimate lumped chemical partitioning and metabolic parameters for a winter blend of gasoline with methyl t-butyl ether and a summer blend without any oxygenate. Computer simulation results from this model matched well with experimental data from single chemical, five-chemical mixture, and the two blends of gasoline. The PBPK model analysis indicated that metabolism of individual components was inhibited up to 27% during the 6-h gas uptake experiments of gasoline exposures.

Respiratory chain complex II as general sensor for apoptosis.

PubMed

Grimm, Stefan

2013-05-01

I review here the evidence that complex II of the respiratory chain (RC) constitutes a general sensor for apoptosis induction. This concept emerged from work on neurodegenerative diseases and from recent data on metabolic alterations in cancer cells affecting the RC and in particular on mutations of complex II subunits. It is also supported by experiments with many anticancer compounds that compared the apoptosis sensitivities of complex II-deficient versus WT cells. These results are explained by the mechanistic understanding of how complex II mediates the diverse range of apoptosis signals. This protein aggregate is specifically activated for apoptosis by pH change as a common and early feature of dying cells. This leads to the dissociation of its SDHA and SDHB subunits from the remaining membrane-anchored subunits and the consequent block of it enzymatic SQR activity, while its SDH activity, which is contained in the SDHA/SDHB subcomplex, remains intact. The uncontrolled SDH activity then generates excessive amounts of reactive oxygen species for the demise of the cell. Future studies on these mitochondrial processes will help refine this model, unravel the contribution of mutations in complex II subunits as the cause of degenerative neurological diseases and tumorigenesis, and aid in discovering novel interference options. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease. Copyright © 2012 Elsevier B.V. All rights reserved.

Tomato fruit chromoplasts behave as respiratory bioenergetic organelles during ripening.

PubMed

Renato, Marta; Pateraki, Irini; Boronat, Albert; Azcón-Bieto, Joaquín

2014-10-01

During tomato (Solanum lycopersicum) fruit ripening, chloroplasts differentiate into photosynthetically inactive chromoplasts. It was recently reported that tomato chromoplasts can synthesize ATP through a respiratory process called chromorespiration. Here we show that chromoplast oxygen consumption is stimulated by the electron donors NADH and NADPH and is sensitive to octyl gallate (Ogal), a plastidial terminal oxidase inhibitor. The ATP synthesis rate of isolated chromoplasts was dependent on the supply of NAD(P)H and was fully inhibited by Ogal. It was also inhibited by the proton uncoupler carbonylcyanide m-chlorophenylhydrazone, suggesting the involvement of a chemiosmotic gradient. In addition, ATP synthesis was sensitive to 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone, a cytochrome b6f complex inhibitor. The possible participation of this complex in chromorespiration was supported by the detection of one of its components (cytochrome f) in chromoplasts using immunoblot and immunocytochemical techniques. The observed increased expression of cytochrome c6 during ripening suggests that it could act as electron acceptor of the cytochrome b6f complex in chromorespiration. The effects of Ogal on respiration and ATP levels were also studied in tissue samples. Oxygen uptake of mature green fruit and leaf tissues was not affected by Ogal, but was inhibited increasingly in fruit pericarp throughout ripening (up to 26% in red fruit). Similarly, Ogal caused a significant decrease in ATP content of red fruit pericarp. The number of energized mitochondria, as determined by confocal microscopy, strongly decreased in fruit tissue during ripening. Therefore, the contribution of chromoplasts to total fruit respiration appears to increase in late ripening stages. © 2014 American Society of Plant Biologists. All Rights Reserved.

Mitochondrial rhodanese: membrane-bound and complexed activity.

PubMed

Ogata, K; Volini, M

1990-05-15

We have proposed that phosphorylated and dephosphorylated forms of the mitochondrial sulfurtransferase, rhodanese, function as converter enzymes that interact with membrane-bound iron-sulfur centers of the electron transport chain to modulate the rate of mitochondrial respiration (Ogata, K., Dai, X., and Volini, M. (1989) J. Biol. Chem. 204, 2718-2725). In the present studies, we have explored some structural aspects of the mitochondrial rhodanese system. By sequential extraction of lysed mitochondria with phosphate buffer and phosphate buffer containing 20 mM cholate, we have shown that 30% of the rhodanese activity of bovine liver is membrane-bound. Resolution of cholate extracts on Sephadex G-100 indicates that part of the bound rhodanese is complexed with other mitochondrial proteins. Tests with the complex show that it forms iron-sulfur centers when incubated with the rhodanese sulfur-donor substrate thiosulfate, iron ions, and a reducing agent. Experiments on the rhodanese activity of rat liver mitochondria give similar results. Taken together, the findings indicate that liver rhodanese is in part bound to the mitochondrial membrane as a component of a multiprotein complex that forms iron-sulfur centers. The findings are consistent with the role we propose for rhodanese in the modulation of mitochondrial respiratory activity.

Metabolic pathway profiling of mitochondrial respiratory chain mutants in C. elegans

PubMed Central

MJ, Falk; Z, Zhang; Rosenjack; Nissim; E, Daikhin; Nissim; MM, Sedensky; M, Yudkoff; PG, Morgan

2008-01-01

C. elegans affords a model of primary mitochondrial dysfunction that provides insight into cellular adaptations which accompany mutations in nuclear gene that encode mitochondrial proteins. To this end, we characterized genome-wide expression profiles of C. elegans strains with mutations in nuclear-encoded subunits of respiratory chain complexes. Our goal was to detect concordant changes among clusters of genes that comprise defined metabolic pathways. Results indicate that respiratory chain mutants significantly upregulate a variety of basic cellular metabolic pathways involved in carbohydrate, amino acid, and fatty acid metabolism, as well as cellular defense pathways such as the metabolism of P450 and glutathione. To further confirm and extend expression analysis findings, quantitation of whole worm free amino acid levels was performed in C. elegans mitochondrial mutants for subunits of complexes I, II, and III. Significant differences were seen for 13 of 16 amino acid levels in complex I mutants compared with controls, as well as overarching similarities among profiles of complex I, II, and III mutants compared with controls. The specific pattern of amino acid alterations observed provides novel evidence to suggest that an increase in glutamate-linked transamination reactions caused by the failure of NAD+ dependent oxidation of ketoacids occurs in primary mitochondrial respiratory chain mutants. Recognition of consistent alterations among patterns of nuclear gene expression for multiple biochemical pathways and in quantitative amino acid profiles in a translational genetic model of mitochondrial dysfunction allows insight into the complex pathogenesis underlying primary mitochondrial disease. Such knowledge may enable the development of a metabolomic profiling diagnostic tool applicable to human mitochondrial disease. PMID:18178500

Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling.

PubMed

Zieliński, Łukasz P; Smith, Anthony C; Smith, Alexander G; Robinson, Alan J

2016-11-01

Mitochondrial respiratory chain dysfunction causes a variety of life-threatening diseases affecting about 1 in 4300 adults. These diseases are genetically heterogeneous, but have the same outcome; reduced activity of mitochondrial respiratory chain complexes causing decreased ATP production and potentially toxic accumulation of metabolites. Severity and tissue specificity of these effects varies between patients by unknown mechanisms and treatment options are limited. So far most research has focused on the complexes themselves, and the impact on overall cellular metabolism is largely unclear. To illustrate how computer modelling can be used to better understand the potential impact of these disorders and inspire new research directions and treatments, we simulated them using a computer model of human cardiomyocyte mitochondrial metabolism containing over 300 characterised reactions and transport steps with experimental parameters taken from the literature. Overall, simulations were consistent with patient symptoms, supporting their biological and medical significance. These simulations predicted: complex I deficiencies could be compensated using multiple pathways; complex II deficiencies had less metabolic flexibility due to impacting both the TCA cycle and the respiratory chain; and complex III and IV deficiencies caused greatest decreases in ATP production with metabolic consequences that parallel hypoxia. Our study demonstrates how results from computer models can be compared to a clinical phenotype and used as a tool for hypothesis generation for subsequent experimental testing. These simulations can enhance understanding of dysfunctional mitochondrial metabolism and suggest new avenues for research into treatment of mitochondrial disease and other areas of mitochondrial dysfunction. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Sleep-disordered breathing after targeted ablation of preBötzinger complex neurons.

PubMed

McKay, Leanne C; Janczewski, Wiktor A; Feldman, Jack L

2005-09-01

Ablation of preBötzinger complex (preBötC) neurons, critical for respiratory rhythm generation, resulted in a progressive, increasingly severe disruption of respiratory pattern, initially during sleep and then also during wakefulness in adult rats. Sleep-disordered breathing is highly prevalent in elderly humans and in some patients with neurodegenerative disease. We propose that sleep-disordered breathing results from loss of preBötC neurons and could underlie death during sleep in these populations.

Sleep-disordered breathing after targeted ablation of preBötzinger complex neurons

PubMed Central

McKay, Leanne C; Janczewski, Wiktor A; Feldman, Jack L

2010-01-01

Ablation of preBötzinger complex (preBötC) neurons, critical for respiratory rhythm generation, resulted in a progressive, increasingly severe disruption of respiratory pattern, initially during sleep and then also during wakefulness in adult rats. Sleep-disordered breathing is highly prevalent in elderly humans and in some patients with neurodegenerative disease. We propose that sleep-disordered breathing results from loss of preBötC neurons and could underlie death during sleep in these populations. PMID:16116455

Distinct respiratory responses of soils to complex organic substrate are governed predominantly by soil architecture and its microbial community.

PubMed

Fraser, F C; Todman, L C; Corstanje, R; Deeks, L K; Harris, J A; Pawlett, M; Whitmore, A P; Ritz, K

2016-12-01

Factors governing the turnover of organic matter (OM) added to soils, including substrate quality, climate, environment and biology, are well known, but their relative importance has been difficult to ascertain due to the interconnected nature of the soil system. This has made their inclusion in mechanistic models of OM turnover or nutrient cycling difficult despite the potential power of these models to unravel complex interactions. Using high temporal-resolution respirometery (6 min measurement intervals), we monitored the respiratory response of 67 soils sampled from across England and Wales over a 5 day period following the addition of a complex organic substrate (green barley powder). Four respiratory response archetypes were observed, characterised by different rates of respiration as well as different time-dependent patterns. We also found that it was possible to predict, with 95% accuracy, which type of respiratory behaviour a soil would exhibit based on certain physical and chemical soil properties combined with the size and phenotypic structure of the microbial community. Bulk density, microbial biomass carbon, water holding capacity and microbial community phenotype were identified as the four most important factors in predicting the soils' respiratory responses using a Bayesian belief network. These results show that the size and constitution of the microbial community are as important as physico-chemical properties of a soil in governing the respiratory response to OM addition. Such a combination suggests that the 'architecture' of the soil, i.e. the integration of the spatial organisation of the environment and the interactions between the communities living and functioning within the pore networks, is fundamentally important in regulating such processes.

Noninvasive ventilation in a child affected by achondroplasia respiratory difficulty syndrome.

PubMed

Ottonello, Giancarlo; Villa, Giovanna; Moscatelli, Andrea; Diana, Maria Cristina; Pavanello, Marco

2007-01-01

Achondroplasia can result in respiratory difficulty in early infancy, from anatomical abnormalities such as mid-facial hypoplasia and/or adenotonsillar hypertrophy, leading to obstructive apnea, or to pathophysiological changes occurring in nasopharyngeal or glossal muscle tone, related to neurological abnormalities (foramen magnum and/or hypoglossal canal problems, hydrocephalus), leading to central apnea. More often, the two respiratory components (central and obstructive) are both evident in mixed apnea. Polysomnographic recording should be used during preoperative and postoperative assessment of achondroplastic children and in the subsequent follow-up to assess the adequacy of continuing home respiratory support, including supplemental oxygen, bilevel positive airway pressure, or assisted ventilation.

21 CFR 522.2260 - Sulfamethazine.

Code of Federal Regulations, 2012 CFR

2012-04-01

... of 5 consecutive days. (2) Indications for use. For cattle for treatment of bacterial pneumonia and bovine respiratory disease complex (shipping fever complex) (Pasteurella spp.), colibacillosis (bacterial...

21 CFR 522.2260 - Sulfamethazine.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of 5 consecutive days. (2) Indications for use. For cattle for treatment of bacterial pneumonia and bovine respiratory disease complex (shipping fever complex) (Pasteurella spp.), colibacillosis (bacterial...

Computerised Analysis of Telemonitored Respiratory Sounds for Predicting Acute Exacerbations of COPD.

PubMed

Fernandez-Granero, Miguel Angel; Sanchez-Morillo, Daniel; Leon-Jimenez, Antonio

2015-10-23

Chronic obstructive pulmonary disease (COPD) is one of the commonest causes of death in the world and poses a substantial burden on healthcare systems and patients' quality of life. The largest component of the related healthcare costs is attributable to admissions due to acute exacerbation (AECOPD). The evidence that might support the effectiveness of the telemonitoring interventions in COPD is limited partially due to the lack of useful predictors for the early detection of AECOPD. Electronic stethoscopes and computerised analyses of respiratory sounds (CARS) techniques provide an opportunity for substantial improvement in the management of respiratory diseases. This exploratory study aimed to evaluate the feasibility of using: (a) a respiratory sensor embedded in a self-tailored housing for ageing users; (b) a telehealth framework; (c) CARS and (d) machine learning techniques for the remote early detection of the AECOPD. In a 6-month pilot study, 16 patients with COPD were equipped with a home base-station and a sensor to daily record their respiratory sounds. Principal component analysis (PCA) and a support vector machine (SVM) classifier was designed to predict AECOPD. 75.8% exacerbations were early detected with an average of 5 ± 1.9 days in advance at medical attention. The proposed method could provide support to patients, physicians and healthcare systems.

21 CFR 520.2170 - Sulfabromomethazine sodium boluses.

Code of Federal Regulations, 2010 CFR

2010-04-01

... pneumonia and bovine respiratory disease complex (shipping fever complex) associated with Pasteurella spp.; acute metritis and acute mastitis caused by Streptococcus spp. (3) Limitations. Administer orally...

Enhanced Respiratory Chain Supercomplex Formation in Response to Exercise in Human Skeletal Muscle.

PubMed

Greggio, Chiara; Jha, Pooja; Kulkarni, Sameer S; Lagarrigue, Sylviane; Broskey, Nicholas T; Boutant, Marie; Wang, Xu; Conde Alonso, Sonia; Ofori, Emmanuel; Auwerx, Johan; Cantó, Carles; Amati, Francesca

2017-02-07

Mitochondrial dysfunction is a hallmark of multiple metabolic complications. Physical activity is known to increase mitochondrial content in skeletal muscle, counteracting age-related decline in muscle function and protecting against metabolic and cardiovascular complications. Here, we investigated the effect of 4 months of exercise training on skeletal muscle mitochondria electron transport chain complexes and supercomplexes in 26 healthy, sedentary older adults. Exercise differentially modulated respiratory complexes. Complex I was the most upregulated complex and not stoichiometrically associated to the other complexes. In contrast to the other complexes, complex I was almost exclusively found assembled in supercomplexes in muscle mitochondria. Overall, supercomplex content was increased after exercise. In particular, complexes I, III, and IV were redistributed to supercomplexes in the form of I+III 2 +IV. Taken together, our results provide the first evidence that exercise affects the stoichiometry of supercomplex formation in humans and thus reveal a novel adaptive mechanism for increased energy demand. Copyright © 2017 Elsevier Inc. All rights reserved.

A reversible component of mitochondrial respiratory dysfunction in apoptosis can be rescued by exogenous cytochrome c

PubMed Central

Mootha, Vamsi K.; Wei, Michael C.; Buttle, Karolyn F.; Scorrano, Luca; Panoutsakopoulou, Vily; Mannella, Carmen A.; Korsmeyer, Stanley J.

2001-01-01

Multiple apoptotic pathways release cytochrome c from the mitochondrial intermembrane space, resulting in the activation of downstream caspases. In vivo activation of Fas (CD95) resulted in increased permeability of the mitochondrial outer membrane and depletion of cytochrome c stores. Serial measurements of oxygen consumption, NADH redox state and membrane potential revealed a loss of respiratory state transitions. This tBID-induced respiratory failure did not require any caspase activity. At early time points, re-addition of exogenous cytochrome c markedly restored respiratory functions. Over time, however, mitochondria showed increasing irreversible respiratory dysfunction as well as diminished calcium buffering. Electron microscopy and tomographic reconstruction revealed asymmetric mitochondria with blebs of herniated matrix, distended inner membrane and partial loss of cristae structure. Thus, apoptogenic redistribution of cytochrome c is responsible for a distinct program of mitochondrial respiratory dysfunction, in addition to the activation of downstream caspases. PMID:11179211

The Cellular Building Blocks of Breathing

PubMed Central

Ramirez, J.M.; Doi, A.; Garcia, A.J.; Elsen, F.P.; Koch, H.; Wei, A.D.

2013-01-01

Respiratory brainstem neurons fulfill critical roles in controlling breathing: they generate the activity patterns for breathing and contribute to various sensory responses including changes in O2 and CO2. These complex sensorimotor tasks depend on the dynamic interplay between numerous cellular building blocks that consist of voltage-, calcium-, and ATP-dependent ionic conductances, various ionotropic and metabotropic synaptic mechanisms, as well as neuromodulators acting on G-protein coupled receptors and second messenger systems. As described in this review, the sensorimotor responses of the respiratory network emerge through the state-dependent integration of all these building blocks. There is no known respiratory function that involves only a small number of intrinsic, synaptic, or modulatory properties. Because of the complex integration of numerous intrinsic, synaptic, and modulatory mechanisms, the respiratory network is capable of continuously adapting to changes in the external and internal environment, which makes breathing one of the most integrated behaviors. Not surprisingly, inspiration is critical not only in the control of ventilation, but also in the context of “inspiring behaviors” such as arousal of the mind and even creativity. Far-reaching implications apply also to the underlying network mechanisms, as lessons learned from the respiratory network apply to network functions in general. PMID:23720262

Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria.

PubMed

Broniarek, Izabela; Jarmuszkiewicz, Wieslawa

2018-01-01

The purpose of this research was to elucidate the direct effects of two popular blood cholesterol-lowering drugs used to treat cardiovascular diseases, atorvastatin and pravastatin, on respiratory function, membrane potential, and reactive oxygen species formation in mitochondria isolated from human umbilical vein endothelial cells (EA.hy926 cell line). Hydrophilic pravastatin did not significantly affect endothelial mitochondria function. In contrast, hydrophobic calcium-containing atorvastatin induced a loss of outer mitochondrial membrane integrity, an increase in hydrogen peroxide formation, and reductions in maximal (phosphorylating or uncoupled) respiratory rate, membrane potential and oxidative phosphorylation efficiency. The atorvastatin-induced changes indicate an impairment of mitochondrial function at the level of ATP synthesis and at the level of the respiratory chain, likely at complex I and complex III. The atorvastatin action on endothelial mitochondria was highly dependent on calcium ions and led to a disturbance in mitochondrial calcium homeostasis. Uptake of calcium ions included in atorvastatin molecule induced mitochondrial uncoupling that enhanced the inhibition of the mitochondrial respiratory chain by atorvastatin. Our results indicate that hydrophobic calcium-containing atorvastatin, widely used as anti-atherosclerotic agent, has a direct negative action on isolated endothelial mitochondria. Copyright © 2017. Published by Elsevier Inc.

A review of concepts regarding the origin of respiratory muscle fatigue

NASA Astrophysics Data System (ADS)

Kuraszkiewicz, Bożena; Piotrkiewicz, Maria

2011-01-01

In this review, the classification of respiratory muscle fatigue from the perspective of its origin is presented. The fatigue is classified as central or peripheral, and the latter further subdivided into high- and low-frequency fatigue. However, muscle fatigue is a complex process and all three types of fatigue probably occur simultaneously in the overloaded respiratory muscles. The relative importance of each type depends on the duration of respiratory loading and other physiological variables. However, central and high-frequency fatigue resolve rapidly once muscle overload is removed, whereas low-frequency fatigue persists over long time.

New and emerging pathogens in canine infectious respiratory disease.

PubMed

Priestnall, S L; Mitchell, J A; Walker, C A; Erles, K; Brownlie, J

2014-03-01

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Jack of All Trades: Pleiotropy and the application of Chemically Modified Tetracycline -3 in Sepsis and the Acute Respiratory Distress Syndrome (ARDS)

PubMed Central

Roy, Shreyas K.; Kendrick, Daniel; Sadowitz, Benjamin D.; Gatto, Louis; Snyder, Kathleen; Satalin, Joshua M.; Golub, Lorne M.; Nieman, Gary

2011-01-01

Sepsis is a disease process that has humbled the medical profession for centuries with its resistance to therapy, relentless mortality, and pathophysiologic complexity. Despite 30 years of aggressive, concerted, well-resourced efforts the biomedical community has been unable to reduce the mortality of sepsis from 30%, nor the mortality of septic shock from greater than 50%. In the last decade only one new drug for sepsis has been brought to the market, drotrecogin alfa-activated (Xigris™), and the success of this drug has been limited by patient safety issues. Clearly a new agent is desperately needed. The advent of recombinant human immune modulators held promise but the outcomes of clinical trials using biologics that target single immune mediators have been disappointing. The complex pathophysiology of the systemic inflammatory response syndrome (SIRS) is self-amplifying and redundant at multiple levels. In this review we argue that perhaps pharmacologic therapy for sepsis will only be successful if it addresses this pathophysiologic complexity; the drug would have to be pleiotropic, working on many components of the inflammatory cascade at once. In this context, therapy that targets any single inflammatory mediator will not adequately address the complexity of SIRS. We propose that Chemically Modified Tetracycline-3, CMT-3 (or COL-3), a non-antimicrobial modified tetracycline with pleiotropic anti-inflammatory properties, is an excellent agent for the management of sepsis and its associated complication of the Acute Respiratory Distress Syndrome (ARDS). The purpose of this review is threefold: 1) to examine the shortcomings of current approaches to treatment of sepsis and ARDS in light of their pathophysiology, 2) to explore the application of COL-3 in ARDS and sepsis, and finally 3) to elucidate the mechanisms of COL-3 that may have potential therapeutic benefit in ARDS and sepsis. PMID:21767646

Systems medicine: a new approach to clinical practice.

PubMed

Cardinal-Fernández, Pablo; Nin, Nicolás; Ruíz-Cabello, Jesús; Lorente, José A

2014-10-01

Most respiratory diseases are considered complex diseases as their susceptibility and outcomes are determined by the interaction between host-dependent factors (genetic factors, comorbidities, etc.) and environmental factors (exposure to microorganisms or allergens, treatments received, etc.) The reductionist approach in the study of diseases has been of fundamental importance for the understanding of the different components of a system. Systems biology or systems medicine is a complementary approach aimed at analyzing the interactions between the different components within one organizational level (genome, transcriptome, proteome), and then between the different levels. Systems medicine is currently used for the interpretation and understanding of the pathogenesis and pathophysiology of different diseases, biomarker discovery, design of innovative therapeutic targets, and the drawing up of computational models for different biological processes. In this review we discuss the most relevant concepts of the theory underlying systems medicine, as well as its applications in the various biological processes in humans. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Breathing and Vocal Control: The Respiratory System as both a Driver and Target of Telencephalic Vocal Motor Circuits in Songbirds

PubMed Central

Schmidt, Marc F.; McLean, Judith; Goller, Franz

2011-01-01

The production of vocalizations is intimately linked to the respiratory system. Despite our understanding of neural circuits that generate normal respiratory patterns, very little is understood regarding how these ponto-medullary circuits become engaged during vocal production. Songbirds offer a potentially powerful model system for addressing this relationship. Songs dramatically alter the respiratory pattern in ways that are often highly predictable and songbirds have a specialized telencephalic vocal motor circuit that provides massive innervation to a brainstem respiratory network that shares many similarities with its mammalian counterpart. In this review, we highlight interactions between the song motor circuit and the respiratory system, describing how both systems likely interact to produce the complex respiratory patterns that are observed during vocalization. We also discuss how the respiratory system, through its bilateral bottom-up projections to thalamus, might play a key role in sending precisely timed signals that synchronize premotor activity in both hemispheres. PMID:21984733

Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers.

PubMed

Lemieux, Hélène; Blier, Pierre U; Gnaiger, Erich

2017-06-06

Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated biases, we studied mitochondrial respiratory control in permeabilized mouse myocardial fibers using high-resolution respirometry. The capacity of oxidative phosphorylation at 37 °C was nearly two-fold higher when fueled by physiological substrate combinations reconstituting tricarboxylic acid cycle function, compared with electron flow measured separately through NADH to Complex I or succinate to Complex II. The relative contribution of the NADH pathway to physiological respiratory capacity increased with a decrease in temperature from 37 to 25 °C. The apparent excess capacity of cytochrome c oxidase above physiological pathway capacity increased sharply under hypothermia due to limitation by NADH-linked dehydrogenases. This mechanism of mitochondrial respiratory control in the hypothermic mammalian heart is comparable to the pattern in ectotherm species, pointing towards NADH-linked mt-matrix dehydrogenases and the phosphorylation system rather than electron transfer complexes as the primary drivers of thermal sensitivity at low temperature. Delineating the link between stress and remodeling of oxidative phosphorylation is important for understanding metabolic perturbations in disease evolution and cardiac protection.

Real-time tumor motion estimation using respiratory surrogate via memory-based learning

NASA Astrophysics Data System (ADS)

Li, Ruijiang; Lewis, John H.; Berbeco, Ross I.; Xing, Lei

2012-08-01

Respiratory tumor motion is a major challenge in radiation therapy for thoracic and abdominal cancers. Effective motion management requires an accurate knowledge of the real-time tumor motion. External respiration monitoring devices (optical, etc) provide a noninvasive, non-ionizing, low-cost and practical approach to obtain the respiratory signal. Due to the highly complex and nonlinear relations between tumor and surrogate motion, its ultimate success hinges on the ability to accurately infer the tumor motion from respiratory surrogates. Given their widespread use in the clinic, such a method is critically needed. We propose to use a powerful memory-based learning method to find the complex relations between tumor motion and respiratory surrogates. The method first stores the training data in memory and then finds relevant data to answer a particular query. Nearby data points are assigned high relevance (or weights) and conversely distant data are assigned low relevance. By fitting relatively simple models to local patches instead of fitting one single global model, it is able to capture highly nonlinear and complex relations between the internal tumor motion and external surrogates accurately. Due to the local nature of weighting functions, the method is inherently robust to outliers in the training data. Moreover, both training and adapting to new data are performed almost instantaneously with memory-based learning, making it suitable for dynamically following variable internal/external relations. We evaluated the method using respiratory motion data from 11 patients. The data set consists of simultaneous measurement of 3D tumor motion and 1D abdominal surface (used as the surrogate signal in this study). There are a total of 171 respiratory traces, with an average peak-to-peak amplitude of ∼15 mm and average duration of ∼115 s per trace. Given only 5 s (roughly one breath) pretreatment training data, the method achieved an average 3D error of 1.5 mm and 95th percentile error of 3.4 mm on unseen test data. The average 3D error was further reduced to 1.4 mm when the model was tuned to its optimal setting for each respiratory trace. In one trace where a few outliers are present in the training data, the proposed method achieved an error reduction of as much as ∼50% compared with the best linear model (1.0 mm versus 2.1 mm). The memory-based learning technique is able to accurately capture the highly complex and nonlinear relations between tumor and surrogate motion in an efficient manner (a few milliseconds per estimate). Furthermore, the algorithm is particularly suitable to handle situations where the training data are contaminated by large errors or outliers. These desirable properties make it an ideal candidate for accurate and robust tumor gating/tracking using respiratory surrogates.

Oxidative phosphorylation in Debaryomyces hansenii: physiological uncoupling at different growth phases.

PubMed

Cabrera-Orefice, Alfredo; Guerrero-Castillo, Sergio; Díaz-Ruíz, Rodrigo; Uribe-Carvajal, Salvador

2014-07-01

Physiological uncoupling of mitochondrial oxidative phosphorylation (OxPhos) was studied in Debaryomyces hansenii. In other species, such as Yarrowia lipolytica and Saccharomyces cerevisiae, OxPhos can be uncoupled through differential expression of branched respiratory chain enzymes or by opening of a mitochondrial unspecific channel (ScMUC), respectively. However D. hansenii mitochondria, which contain both a branched respiratory chain and a mitochondrial unspecific channel (DhMUC), selectively uncouple complex I-dependent rate of oxygen consumption in the stationary growth phase. The uncoupled complex I-dependent respiration was only 20% of the original activity. Inhibition was not due to inactivation of complex I, lack of protein expression or to differential expression of alternative oxidoreductases. Furthermore, all other respiratory chain activities were normal. Decrease of complex I-dependent respiration was due to NAD(+) loss from the matrix, probably through an open of DhMUC. When NAD(+) was added back, coupled complex I-activity was recovered. NAD(+) re-uptake was independent of DhMUC opening and seemed to be catalyzed by a NAD(+)-specific transporter, which was sensitive to bathophenanthroline, bromocresol purple or pyridoxal-5'-phosphate as described for S. cerevisiae mitochondrial NAD(+) transporters. Loss of NAD(+) from the matrix through an open MUC is proposed as an additional mechanism to uncouple OxPhos. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Progressive Changes in a Distributed Neural Circuit Underlie Breathing Abnormalities in Mice Lacking MeCP2.

PubMed

Huang, Teng-Wei; Kochukov, Mikhail Y; Ward, Christopher S; Merritt, Jonathan; Thomas, Kaitlin; Nguyen, Tiffani; Arenkiel, Benjamin R; Neul, Jeffrey L

2016-05-18

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Severe breathing abnormalities are common in RTT and are reproduced in mouse models of RTT. Previously, we found that removing MeCP2 from the brainstem and spinal cord in mice caused early lethality and abnormal breathing. To determine whether loss of MeCP2 in functional components of the respiratory network causes specific breathing disorders, we used the Cre/LoxP system to differentially manipulate MeCP2 expression throughout the brainstem respiratory network, specifically within HoxA4-derived tissues, which include breathing control circuitry within the nucleus tractus solitarius and the caudal part of ventral respiratory column but do not include more rostral parts of the breathing control circuitry. To determine whether respiratory phenotypes manifested in animals with MeCP2 removed from specific pons medullary respiratory circuits, we performed whole-body plethysmography and electrophysiological recordings from in vitro brainstem slices from mice lacking MeCP2 in different circuits. Our results indicate that MeCP2 expression in the medullary respiratory network is sufficient for normal respiratory rhythm and preventing apnea. However, MeCP2 expression within components of the breathing circuitry rostral to the HoxA4 domain are neither sufficient to prevent the hyperventilation nor abnormal hypoxic ventilatory response. Surprisingly, we found that MeCP2 expression in the HoxA4 domain alone is critical for survival. Our study reveals that MeCP2 is differentially required in select respiratory components for different aspects of respiratory functions, and collectively for the integrity of this network functions to maintain proper respiration. Breathing abnormalities are a significant clinical feature in Rett syndrome and are robustly reproduced in the mouse models of this disease. Previous work has established that alterations in the function of MeCP2, the protein encoded by the gene mutated in Rett syndrome, within the hindbrain are critical for control of normal breathing. Here we show that MeCP2 function plays distinct roles in specific brainstem regions in the genesis of various aspects of abnormal breathing. This provides insight into the pathogenesis of these breathing abnormalities in Rett syndrome, which could be used to target treatments to improve these symptoms. Furthermore, it provides further knowledge about the fundamental neural circuits that control breathing. Copyright © 2016 the authors 0270-6474/16/365572-15$15.00/0.

Absence of Complex I Is Associated with Diminished Respiratory Chain Function in European Mistletoe.

PubMed

Maclean, Andrew E; Hertle, Alexander P; Ligas, Joanna; Bock, Ralph; Balk, Janneke; Meyer, Etienne H

2018-05-21

Parasitism is a life history strategy found across all domains of life whereby nutrition is obtained from a host. It is often associated with reductive evolution of the genome, including loss of genes from the organellar genomes [1, 2]. In some unicellular parasites, the mitochondrial genome (mitogenome) has been lost entirely, with far-reaching consequences for the physiology of the organism [3, 4]. Recently, mitogenome sequences of several species of the hemiparasitic plant mistletoe (Viscum sp.) have been reported [5, 6], revealing a striking loss of genes not seen in any other multicellular eukaryotes. In particular, the nad genes encoding subunits of respiratory complex I are all absent and other protein-coding genes are also lost or highly diverged in sequence, raising the question what remains of the respiratory complexes and mitochondrial functions. Here we show that oxidative phosphorylation (OXPHOS) in European mistletoe, Viscum album, is highly diminished. Complex I activity and protein subunits of complex I could not be detected. The levels of complex IV and ATP synthase were at least 5-fold lower than in the non-parasitic model plant Arabidopsis thaliana, whereas alternative dehydrogenases and oxidases were higher in abundance. Carbon flux analysis indicates that cytosolic reactions including glycolysis are greater contributors to ATP synthesis than the mitochondrial tricarboxylic acid (TCA) cycle. Our results describe the extreme adjustments in mitochondrial functions of the first reported multicellular eukaryote without complex I. Copyright © 2018 Elsevier Ltd. All rights reserved.

Self-Collected Nasal Swabs for Respiratory Virus Surveillance

PubMed Central

Jackson, Michael L.; Nguyen, Matthew; Kirlin, Beth; Madziwa, Lawrence

2015-01-01

We tested whether 135 patients reporting acute respiratory illness (ARI) could self-collect nasal swab specimens and ship them for laboratory testing. Most subjects (78.2%) collected and shipped their specimens without errors; 10.5% excluded ≥1 packing components; 12.9% made ≥1 packing errors. Self-swabbing at home is feasible for confirming ARI etiology. PMID:26613095

Human organoid cultures: transformative new tools for human virus studies.

PubMed

Ramani, Sasirekha; Crawford, Sue E; Blutt, Sarah E; Estes, Mary K

2018-04-01

Studies of human infectious diseases have been limited by the paucity of functional models that mimic normal human physiology and pathophysiology. Recent advances in the development of multicellular, physiologically active organotypic cultures produced from embryonic and pluripotent stem cells, as well as from stem cells isolated from biopsies and surgical specimens are allowing unprecedented new studies and discoveries about host-microbe interactions. Here, we summarize recent developments in the use of organoids for studying human viral pathogens, including intestinal infections with human rotavirus, norovirus, enteroviruses and adenoviruses (intestinal organoids and enteroids), neuronal infections with Zika virus (cerebral organoids) and respiratory infections with respiratory syncytial virus in (lung bud organoids). Biologic discovery of host-specific genetic and epigenetic factors affecting infection, and responses to infection that lead to disease are possible with the use of organoid cultures. Continued development to increase the complexity of these cultures by including components of the normal host tissue microenvironment such as immune cells, blood vessels and microbiome, will facilitate studies on human viral pathogenesis, and advance the development of platforms for pre-clinical evaluation of vaccines, antivirals and therapeutics. Copyright © 2018 Elsevier B.V. All rights reserved.

Transfer function for vital infrasound pressures between the carotid artery and the tympanic membrane.

PubMed

Furihata, Kenji; Yamashita, Masato

2013-02-01

While occupational injury is associated with numerous individual and work-related risk factors, including long working hours and short sleep duration, the complex mechanisms causing such injuries are not yet fully understood. The relationship between the infrasound pressures of the tympanic membrane [ear canal pressure (ECP)], detected using an earplug embedded with a low-frequency microphone, and the carotid artery [carotid artery pressure (CAP)], detected using a stethoscope fitted with the same microphone, can be quantitatively characterized using systems analysis. The transfer functions of 40 normal workers (19 to 57 years old) were characterized, involving the analysis of 446 data points. The ECP waveform exhibits a pulsatile character with a slow respiratory component, which is superimposed on a biphasic recording that is synchronous with the cardiac cycle. The respiratory ECP waveform correlates with the instantaneous heart rate. The results also revealed that various fatigue-related risk factors may affect the mean magnitudes of the measured pressures and the delay transfer functions between CAP and ECP in the study population; these factors include systolic blood pressure, salivary amylase activity, age, sleep duration, postural changes, chronic fatigue, and pulse rate.

Respiratory chain components involved in the glycerophosphate dehydrogenase-dependent ROS production by brown adipose tissue mitochondria.

PubMed

Vrbacký, Marek; Drahota, Zdenek; Mrácek, Tomás; Vojtísková, Alena; Jesina, Pavel; Stopka, Pavel; Houstek, Josef

2007-07-01

Involvement of mammalian mitochondrial glycerophosphate dehydrogenase (mGPDH, EC 1.1.99.5) in reactive oxygen species (ROS) generation was studied in brown adipose tissue mitochondria by different spectroscopic techniques. Spectrofluorometry using ROS-sensitive probes CM-H2DCFDA and Amplex Red was used to determine the glycerophosphate- or succinate-dependent ROS production in mitochondria supplemented with respiratory chain inhibitors antimycin A and myxothiazol. In case of glycerophosphate oxidation, most of the ROS originated directly from mGPDH and coenzyme Q while complex III was a typical site of ROS production in succinate oxidation. Glycerophosphate-dependent ROS production monitored by KCN-insensitive oxygen consumption was highly activated by one-electron acceptor ferricyanide, whereas succinate-dependent ROS production was unaffected. In addition, superoxide anion radical was detected as a mGPDH-related primary ROS species by fluorescent probe dihydroethidium, as well as by electron paramagnetic resonance (EPR) spectroscopy with DMPO spin trap. Altogether, the data obtained demonstrate pronounced differences in the mechanism of ROS production originating from oxidation of glycerophosphate and succinate indicating that electron transfer from mGPDH to coenzyme Q is highly prone to electron leak and superoxide generation.

A Functional Approach towards Understanding the Role of the Mitochondrial Respiratory Chain in an Endomycorrhizal Symbiosis

PubMed Central

Mercy, Louis; Lucic-Mercy, Eva; Nogales, Amaia; Poghosyan, Areg; Schneider, Carolin; Arnholdt-Schmitt, Birgit

2017-01-01

Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and legislative contexts should drive the so-called “second green revolution” by better exploiting these beneficial microorganisms. Many challenges still need to be overcome to better understand the mycorrhizal symbiosis, among which (i) the biotrophic nature of AMF, constraining their production, while (ii) phosphate acts as a limiting factor for the optimal mycorrhizal inoculum application and effectiveness. Organism fitness and adaptation to the changing environment can be driven by the modulation of mitochondrial respiratory chain, strongly connected to the phosphorus processing. Nevertheless, the role of the respiratory function in mycorrhiza remains largely unexplored. We hypothesized that the two mitochondrial respiratory chain components, alternative oxidase (AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal behavior. For this, a complex approach was developed. At the pre-symbiotic phase (axenic conditions), we studied phenotypic responses of Rhizoglomus irregulare spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid (SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid – ABA and gibberellic acid – Ga3). At the symbiotic phase, we analyzed phenotypic and transcriptomic (genes involved in respiration, transport, and fermentation) responses in Solanum tuberosum/Rhizoglomus irregulare biosystem (glasshouse conditions): we monitored the effects driven by ABA, and explored the modulations induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM inhibited in vitro spore germination while ABA and Ga3 induced differential spore germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA treated plants, R. irregulare induced down-regulation of StAOX gene isoforms and up-regulation of genes involved in plant COX pathway. In all phosphorus (P) concentrations, blocking AOX or COX induced opposite mycorrhizal patterns in planta: KCN induced higher Arum-type arbuscule density, positive MGD but lower root colonization compared to SHAM, which favored Paris-type formation and negative MGD. Following our results and current state-of-the-art knowledge, we discuss metabolic functions linked to respiration that may occur within mycorrhizal behavior. We highlight potential connections between AOX pathways and fermentation, and we propose new research and mycorrhizal application perspectives. PMID:28424712

Acoustic phenomena observed in lung auscultation

NASA Astrophysics Data System (ADS)

Korenbaum, V. I.; Tagil'Tsev, A. A.; Kulakov, Yu. V.

2003-05-01

The results of studying respiratory noise at the chest wall by the method of acoustic intensimetry reveal the presence of frequency components with different signs of the real and imaginary parts of the cross spectrum obtained for the responses of the receivers of vibratory displacement and dynamic force. An acoustic model is proposed to explain this difference on the basis of the hypothesis that the contributions of both air-borne and structure-borne sound are significant in the transmission of respiratory noise to the chest wall. It is shown that, when considered as an acoustic channel for the basic respiratory noise, the respiratory system of an adult subject has two resonances: in the frequency bands within 110 150 and 215 350 Hz. For adults in normal condition, the air-borne component of the basic respiratory noise predominates in the region 100 300 Hz in the lower parts of lungs. At forced respiration of healthy adults, the sounds of vesicular respiration are generated by the turbulent air flow in the 11th-through 13th-generation bronchi, and the transmission of these sounds to the chest wall in normal condition is mainly through air and is determined by the resonance of the vibratory system formed by the elasticity of air in the respiratory ducts of lungs and by the surface mass density of the chest wall. It is demonstrated that the distance from the chest wall to the sources of structure-borne additional respiratory noise, namely, wheezing with frequencies above 300 Hz, can be estimated numerically from the ratio between the real and imaginary parts of the cross spectrum on the assumption that the source is of the quadrupole type.

Bacterial lysates improve the protective antibody response against respiratory viruses through Toll-like receptor 4

PubMed Central

Coviello, Silvina; Wimmenauer, Vera; Polack, Fernando P; Irusta, Pablo M

2014-01-01

Respiratory viruses cause significant morbidity and mortality in infants and young children worldwide. Current strategies to modulate the immune system and prevent or treat respiratory viral infections in this age group have shown limited success. Here, we demonstrate that a lysate derived from Gram-positive and Gram-negative organisms positively modulates protective antibody responses against both respiratory syncytial virus (RSV) and influenza virus in murine models of infection. Interestingly, despite the complex mixture of Toll-like receptor (TLR) agonists present in the bacterial lysate, the modulatory effects were mostly dependent on TLR4 signaling. Our results indicate that the use of simple formulations of TLR-agonists can significantly improve the immune response against critical pediatric respiratory pathogens. PMID:25483455

Relative virulence in bison and cattle of bison-associated genotypes of Mycoplasma bovis

USDA-ARS?s Scientific Manuscript database

Background. Mycoplasma bovis is a cause of respiratory disease in cattle and the bacterium most frequently isolated from bovine respiratory disease complex. It has recently emerged as a major health problem in bison, causing pharyngitis, pneumonia, arthritis, dystocia and abortion. In cattle, M. b...

Identification of gene biomarkers for respiratory synctial virus infection in a bronchical epithelial cell line

EPA Science Inventory

Abstract: Respiratory syncytial virus (RSV) infection involves complex virus-host interplay. In this study, we analyzed gene expression in RSV-infected BEAS-2B cells to discover novel signaling pathways and biomarkers. We hybridized RNAs from RSV- or vehicle-treated BEAS-2B to ...

FACTORS MODULATING THE EPITHELIAL RESPONSE TO TOXICANTS IN TRACHEOBRONCHIAL AIRWAYS. (R827442)

EPA Science Inventory

As one of the principal interfaces between the organism and the environment, the respiratory system is a target for a wide variety of toxicants and carcinogens. The cellular and architectural complexity of the respiratory system appears to play a major role in defining the foc...

Kinetics and Mechanism of Mammalian Mitochondrial Ribosome Assembly.

PubMed

Bogenhagen, Daniel F; Ostermeyer-Fay, Anne G; Haley, John D; Garcia-Diaz, Miguel

2018-02-13

Mammalian mtDNA encodes only 13 proteins, all essential components of respiratory complexes, synthesized by mitochondrial ribosomes. Mitoribosomes contain greatly truncated RNAs transcribed from mtDNA, including a structural tRNA in place of 5S RNA as a scaffold for binding 82 nucleus-encoded proteins, mitoribosomal proteins (MRPs). Cryoelectron microscopy (cryo-EM) studies have determined the structure of the mitoribosome, but its mechanism of assembly is unknown. Our SILAC pulse-labeling experiments determine the rates of mitochondrial import of MRPs and their assembly into intact mitoribosomes, providing a basis for distinguishing MRPs that bind at early and late stages in mitoribosome assembly to generate a working model for mitoribosome assembly. Mitoribosome assembly is a slow process initiated at the mtDNA nucleoid driven by excess synthesis of individual MRPs. MRPs that are tightly associated in the structure frequently join the complex in a coordinated manner. Clinically significant MRP mutations reported to date affect proteins that bind early on during assembly. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Mitochondrial protein hyperacetylation in the failing heart

PubMed Central

Horton, Julie L.; Martin, Ola J.; Lai, Ling; Richards, Alicia L.; Vega, Rick B.; Leone, Teresa C.; Pagliarini, David J.; Muoio, Deborah M.; Bedi, Kenneth C.; Coon, Joshua J.

2016-01-01

Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothesized that accumulation of metabolite intermediates of fuel oxidation pathways drives posttranslational modifications of mitochondrial proteins during the development of heart failure. Myocardial acetylproteomics demonstrated extensive mitochondrial protein lysine hyperacetylation in the early stages of heart failure in well-defined mouse models and the in end-stage failing human heart. To determine the functional impact of increased mitochondrial protein acetylation, we focused on succinate dehydrogenase A (SDHA), a critical component of both the tricarboxylic acid (TCA) cycle and respiratory complex II. An acetyl-mimetic mutation targeting an SDHA lysine residue shown to be hyperacetylated in the failing human heart reduced catalytic function and reduced complex II–driven respiration. These results identify alterations in mitochondrial acetyl-CoA homeostasis as a potential driver of the development of energy metabolic derangements that contribute to heart failure. PMID:26998524

Mitochondrial protein hyperacetylation in the failing heart.

PubMed

Horton, Julie L; Martin, Ola J; Lai, Ling; Riley, Nicholas M; Richards, Alicia L; Vega, Rick B; Leone, Teresa C; Pagliarini, David J; Muoio, Deborah M; Bedi, Kenneth C; Margulies, Kenneth B; Coon, Joshua J; Kelly, Daniel P

2016-02-01

Myocardial fuel and energy metabolic derangements contribute to the pathogenesis of heart failure. Recent evidence implicates posttranslational mechanisms in the energy metabolic disturbances that contribute to the pathogenesis of heart failure. We hypothesized that accumulation of metabolite intermediates of fuel oxidation pathways drives posttranslational modifications of mitochondrial proteins during the development of heart failure. Myocardial acetylproteomics demonstrated extensive mitochondrial protein lysine hyperacetylation in the early stages of heart failure in well-defined mouse models and the in end-stage failing human heart. To determine the functional impact of increased mitochondrial protein acetylation, we focused on succinate dehydrogenase A (SDHA), a critical component of both the tricarboxylic acid (TCA) cycle and respiratory complex II. An acetyl-mimetic mutation targeting an SDHA lysine residue shown to be hyperacetylated in the failing human heart reduced catalytic function and reduced complex II-driven respiration. These results identify alterations in mitochondrial acetyl-CoA homeostasis as a potential driver of the development of energy metabolic derangements that contribute to heart failure.

Respiratory Complex I in Bos taurus and Paracoccus denitrificans Pumps Four Protons across the Membrane for Every NADH Oxidized.

PubMed

Jones, Andrew J Y; Blaza, James N; Varghese, Febin; Hirst, Judy

2017-03-24

Respiratory complex I couples electron transfer between NADH and ubiquinone to proton translocation across an energy-transducing membrane to support the proton-motive force that drives ATP synthesis. The proton-pumping stoichiometry of complex I ( i.e. the number of protons pumped for each two electrons transferred) underpins all mechanistic proposals. However, it remains controversial and has not been determined for any of the bacterial enzymes that are exploited as model systems for the mammalian enzyme. Here, we describe a simple method for determining the proton-pumping stoichiometry of complex I in inverted membrane vesicles under steady-state ADP-phosphorylating conditions. Our method exploits the rate of ATP synthesis, driven by oxidation of NADH or succinate with different sections of the respiratory chain engaged in catalysis as a proxy for the rate of proton translocation and determines the stoichiometry of complex I by reference to the known stoichiometries of complexes III and IV. Using vesicles prepared from mammalian mitochondria (from Bos taurus ) and from the bacterium Paracoccus denitrificans , we show that four protons are pumped for every two electrons transferred in both cases. By confirming the four-proton stoichiometry for mammalian complex I and, for the first time, demonstrating the same value for a bacterial complex, we establish the utility of P. denitrificans complex I as a model system for the mammalian enzyme. P. denitrificans is the first system described in which mutagenesis in any complex I core subunit may be combined with quantitative proton-pumping measurements for mechanistic studies. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Mitochondrial Ca2+ influx targets cardiolipin to disintegrate respiratory chain complex II for cell death induction

PubMed Central

Hwang, M-S; Schwall, C T; Pazarentzos, E; Datler, C; Alder, N N; Grimm, S

2014-01-01

Massive Ca2+ influx into mitochondria is critically involved in cell death induction but it is unknown how this activates the organelle for cell destruction. Using multiple approaches including subcellular fractionation, FRET in intact cells, and in vitro reconstitutions, we show that mitochondrial Ca2+ influx prompts complex II of the respiratory chain to disintegrate, thereby releasing an enzymatically competent sub-complex that generates excessive reactive oxygen species (ROS) for cell death induction. This Ca2+-dependent dissociation of complex II is also observed in model membrane systems, but not when cardiolipin is replaced with a lipid devoid of Ca2+ binding. Cardiolipin is known to associate with complex II and upon Ca2+ binding coalesces into separate homotypic clusters. When complex II is deprived of this lipid, it disintegrates for ROS formation and cell death. Our results reveal Ca2+ binding to cardiolipin for complex II disintegration as a pivotal step for oxidative stress and cell death induction. PMID:24948011

The long story of mitochondrial DNA and respiratory complex I.

PubMed

Degli Esposti, Mauro

2017-01-01

This article examines the long story of the relationship between mitochondrial DNA (mtDNA) and respiratory complex I, NADH:Ubiquinone Oxidoreductase, from its beginning  in the genome of the bacterial endosymbiont which then evolved into the mitochondria of our cells. The story begins with the evolution of ancient forms of bacterial complex I into the Nuo14 complex I that was present in the alpha proteobacterial ancestor of mitochondria. The story then becomes complicated in the diversity of eukaryotic organisms that are currently recognized. Therefore, it does not have a clear end, because currently available information shows different situations of metabolic adaptation and gene loss, indicating cases of de-evolution of the original protonmotive complex into a system that may fundamentally assist [FeFe]-hydrogenases in re-oxidising metabolically produced NADH under anaerobic conditions. The history of complex I is thus a never ending story of molecular and physiological evolution producing new perspectives for studying the enzyme complex that occupies the largest proportion of mitochondrial DNA.

Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23.

PubMed

Hirawake, H; Taniwaki, M; Tamura, A; Kojima, S; Kita, K

1997-01-01

Complex II (succinate-ubiquinone oxidoreductase) is an important enzyme complex in both the tricarboxylic acid cycle and the aerobic respiratory chains of mitochondria in eukaryotic cells and prokaryotic organisms. In this study, the amino acid sequences of the large (cybL) and small (cybS) subunits of cytochrome b in human liver complex II were deduced from cDNAs isolated by homology probing with mixed primers for the polymerase chain reaction. The mature cybL and cybS contain 140 and 103 amino acids, respectively, and show little similarity to the amino acid sequences of the subunits from other species in contrast to the highly conserved features of the flavoprotein (Fp) subunit and iron-sulfur protein (Ip) subunit. From hydrophobicity analysis, both cybL and cybS appear to have three transmembrane segments, indicating their role as membrane-anchors for the enzyme complex. Histidine residues, which are possible heme axial ligands in cytochrome b of complex II, were found in the second transmembrane segment of each subunit. The genes for cybL (SDHC) and cybS (SDHD) were mapped to chromosome 1q21 and 11q23, respectively by fluorescent in situ hybridization (FISH).

User's instructions for the Grodins' respiratory control model using the UNIVAC 1110 remote batch and demand processing

NASA Technical Reports Server (NTRS)

1974-01-01

The transient and steady state response of the respiratory control system for variations in volumetric fractions of inspired gases and special system parameters are modeled. The program contains the capability to change workload. The program is based on Grodins' respiratory control model and can be envisioned as a feedback control system comprised of a plant (the controlled system) and the regulating component (controlling system). The controlled system is partitioned into 3 compartments corresponding to lungs, brain, and tissue with a fluid interconnecting patch representing the blood.

[Mitochondrial disease due to the deficit of Q-cytochrome C oxidoreductase coenzyme in the respiratory chain. Report of a new case].

PubMed

Roldán, S; Lluch, M D; Navarro Quesada, F J; Hevia, A

1995-01-01

Reference has been made in the literature of the variability in the clinical presentation of deficiency of complex III of the respiratory chain, identifying up to the moment, four groups, the first of which is characterized by hipotonia and wearness starting at variable ages. We report a new case of mitochondrial myopathy due to deficiency of this complex and included within this first group, and consider the importance of defining the clinical and histochemical characteristics of this polymorphous entity.

A UWB Radar Signal Processing Platform for Real-Time Human Respiratory Feature Extraction Based on Four-Segment Linear Waveform Model.

PubMed

Hsieh, Chi-Hsuan; Chiu, Yu-Fang; Shen, Yi-Hsiang; Chu, Ta-Shun; Huang, Yuan-Hao

2016-02-01

This paper presents an ultra-wideband (UWB) impulse-radio radar signal processing platform used to analyze human respiratory features. Conventional radar systems used in human detection only analyze human respiration rates or the response of a target. However, additional respiratory signal information is available that has not been explored using radar detection. The authors previously proposed a modified raised cosine waveform (MRCW) respiration model and an iterative correlation search algorithm that could acquire additional respiratory features such as the inspiration and expiration speeds, respiration intensity, and respiration holding ratio. To realize real-time respiratory feature extraction by using the proposed UWB signal processing platform, this paper proposes a new four-segment linear waveform (FSLW) respiration model. This model offers a superior fit to the measured respiration signal compared with the MRCW model and decreases the computational complexity of feature extraction. In addition, an early-terminated iterative correlation search algorithm is presented, substantially decreasing the computational complexity and yielding negligible performance degradation. These extracted features can be considered the compressed signals used to decrease the amount of data storage required for use in long-term medical monitoring systems and can also be used in clinical diagnosis. The proposed respiratory feature extraction algorithm was designed and implemented using the proposed UWB radar signal processing platform including a radar front-end chip and an FPGA chip. The proposed radar system can detect human respiration rates at 0.1 to 1 Hz and facilitates the real-time analysis of the respiratory features of each respiration period.

The Enigma of the Respiratory Chain Supercomplex.

PubMed

Milenkovic, Dusanka; Blaza, James N; Larsson, Nils-Göran; Hirst, Judy

2017-04-04

Respiratory chain dysfunction plays an important role in human disease and aging. It is now well established that the individual respiratory complexes can be organized into supercomplexes, and structures for these macromolecular assemblies, determined by electron cryo-microscopy, have been described recently. Nevertheless, the reason why supercomplexes exist remains an enigma. The widely held view that they enhance catalysis by channeling substrates is challenged by both structural and biophysical information. Here, we evaluate and discuss data and hypotheses on the structures, roles, and assembly of respiratory-chain supercomplexes and propose a future research agenda to address unanswered questions. Copyright © 2017. Published by Elsevier Inc.

Cross-reactivity between aeroallergens and food allergens

PubMed Central

Popescu, Florin-Dan

2015-01-01

In patients with respiratory allergy, cross-reactivity between aeroallergens and foods may induce food allergy, symptoms ranging from oral allergy syndrome to severe anaphylaxis. Clinical entities due to IgE sensitization to cross-reactive aeroallergen and food allergen components are described for many sources of plant origin (pollen-food syndromes and associations, such as birch-apple, cypress-peach and celery-mugwort-spice syndromes, and mugwort-peach, mugwort-chamomile, mugwort-mustard, ragweed-melon-banana, goosefoot-melon associations), fungal origin (Alternaria-spinach syndrome), and invertebrate, mammalian or avian origin (mite-shrimp, cat-pork, and bird-egg syndromes). Clinical cases of allergic reactions to ingestion of food products containing pollen grains of specific plants, in patients with respiratory allergy to Asteraceae pollen, especially mugwort and ragweed, are also mentioned, for honey, royal jelly and bee polen dietary supplements, along with allergic reactions to foods contaminated with mites or fungi in patients with respiratory allergy to these aeroallergens. Medical history and diagnosis approach may be guided by the knowledge about the diverse cross-reacting allergens involved, and by the understanding of these clinical entities which may vary significantly or may be overlapping. The association between primary IgE sensitization with respiratory symptoms to inhaled allergens and food allergy due to cross-reactive allergen components is important to assess in allergy practice. The use of molecular-based diagnosis improves the understanding of clinically relevant IgE sensitization to cross-reactive allergen components from aeroallergen sources and foods. PMID:26140270

The effect of lactic acidosis on the generation and compensation of mixed respiratory-metabolic acidosis in neonatal calves.

PubMed

Bleul, U; Götz, E

2013-05-18

Postnatal mixed respiratory-metabolic acidosis is common in calves, and depending on its severity can impair vitality or even cause death. Carbon dioxide accounts for the respiratory component and L-lactate for the metabolic component of the mixed acidosis, but it remains unclear which component determines the severity and duration of the acidosis. In a first attempt to clarify, this was investigated retrospectively in 31 calves during the first two hours of life, and in 13 calves during the first three days of life. Venous blood was collected for blood gas analysis and measurement of acid-base variables and L-lactate concentration. pH Was more strongly correlated with L-lactate concentration (r(2)=0.808) than with partial pressure of CO2 (pCO2, r(2)=0.418). Duration of parturition had a distinct effect on pH and L-lactate concentration but not on pCO2; calves born within six hours of rupture of the allantoic sac had a higher pH and lower L-lactate concentration than calves born after a longer duration of parturition (both P<0.01). Normalisation of pCO2 took four hours and normalisation of L-lactate took 48 hours. It was concluded that L-lactate is a more important factor in the pathogenesis of acidosis than pCO2, and that the duration of metabolic acidosis exceeds that of respiratory acidosis in perinatal asphyxia of calves.

Integrative approaches for modeling regulation and function of the respiratory system.

PubMed

Ben-Tal, Alona; Tawhai, Merryn H

2013-01-01

Mathematical models have been central to understanding the interaction between neural control and breathing. Models of the entire respiratory system-which comprises the lungs and the neural circuitry that controls their ventilation-have been derived using simplifying assumptions to compartmentalize each component of the system and to define the interactions between components. These full system models often rely-through necessity-on empirically derived relationships or parameters, in addition to physiological values. In parallel with the development of whole respiratory system models are mathematical models that focus on furthering a detailed understanding of the neural control network, or of the several functions that contribute to gas exchange within the lung. These models are biophysically based, and rely on physiological parameters. They include single-unit models for a breathing lung or neural circuit, through to spatially distributed models of ventilation and perfusion, or multicircuit models for neural control. The challenge is to bring together these more recent advances in models of neural control with models of lung function, into a full simulation for the respiratory system that builds upon the more detailed models but remains computationally tractable. This requires first understanding the mathematical models that have been developed for the respiratory system at different levels, and which could be used to study how physiological levels of O2 and CO2 in the blood are maintained. Copyright © 2013 Wiley Periodicals, Inc.

Health effects of environmental pollution in population living near industrial complex areas in Korea.

PubMed

Eom, Sang-Yong; Choi, Jonghyuk; Bae, Sanghyuk; Lim, Ji-Ae; Kim, Guen-Bae; Yu, Seung-Do; Kim, Yangho; Lim, Hyun-Sul; Son, Bu-Soon; Paek, Domyung; Kim, Yong-Dae; Kim, Heon; Ha, Mina; Kwon, Ho-Jang

2018-01-01

Several epidemiological studies have reported an association between environmental pollution and various health conditions in individuals residing in industrial complexes. To evaluate the effects of pollution from industrial complex on human health, we performed a pooled analysis of environmental epidemiologic monitoring data for residents living near national industrial complexes in Korea. The respiratory and allergic symptoms and the prevalence of acute and chronic diseases, including cancer, were used as the outcome variables for health effects. Multiple logistic regression analysis was used to analyze the relationship between exposure to pollution from industrial complexes and health conditions. After adjusting for age, sex, smoking status, occupational exposure, level of education, and body mass index, the residents near the industrial complexes were found to have more respiratory symptoms, such as cough (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.06 to 1.31) and sputum production (OR, 1.13; 95% CI, 1.03 to 1.24), and symptoms of atopic dermatitis (OR, 1.10; 95% CI, 1.01 to 1.20). Among residents of the industrial complexes, the prevalence of acute eye disorders was approximately 40% higher (OR, 1.39; 95% CI, 1.04 to 1.84) and the prevalence of lung and uterine cancer was 3.45 times and 1.88 times higher, respectively, than those among residents of the control area. This study showed that residents living in the vicinity of industrial complexes have a high risk of acute and chronic diseases including respiratory and allergic conditions. These results can be used as basic objective data for developing health management measures for individuals residing near industrial complexes.

Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.

PubMed

Taylor, Robert W; Pyle, Angela; Griffin, Helen; Blakely, Emma L; Duff, Jennifer; He, Langping; Smertenko, Tania; Alston, Charlotte L; Neeve, Vivienne C; Best, Andrew; Yarham, John W; Kirschner, Janbernd; Schara, Ulrike; Talim, Beril; Topaloglu, Haluk; Baric, Ivo; Holinski-Feder, Elke; Abicht, Angela; Czermin, Birgit; Kleinle, Stephanie; Morris, Andrew A M; Vassallo, Grace; Gorman, Grainne S; Ramesh, Venkateswaran; Turnbull, Douglass M; Santibanez-Koref, Mauro; McFarland, Robert; Horvath, Rita; Chinnery, Patrick F

2014-07-02

Mitochondrial disorders have emerged as a common cause of inherited disease, but their diagnosis remains challenging. Multiple respiratory chain complex defects are particularly difficult to diagnose at the molecular level because of the massive number of nuclear genes potentially involved in intramitochondrial protein synthesis, with many not yet linked to human disease. To determine the molecular basis of multiple respiratory chain complex deficiencies. We studied 53 patients referred to 2 national centers in the United Kingdom and Germany between 2005 and 2012. All had biochemical evidence of multiple respiratory chain complex defects but no primary pathogenic mitochondrial DNA mutation. Whole-exome sequencing was performed using 62-Mb exome enrichment, followed by variant prioritization using bioinformatic prediction tools, variant validation by Sanger sequencing, and segregation of the variant with the disease phenotype in the family. Presumptive causal variants were identified in 28 patients (53%; 95% CI, 39%-67%) and possible causal variants were identified in 4 (8%; 95% CI, 2%-18%). Together these accounted for 32 patients (60% 95% CI, 46%-74%) and involved 18 different genes. These included recurrent mutations in RMND1, AARS2, and MTO1, each on a haplotype background consistent with a shared founder allele, and potential novel mutations in 4 possible mitochondrial disease genes (VARS2, GARS, FLAD1, and PTCD1). Distinguishing clinical features included deafness and renal involvement associated with RMND1 and cardiomyopathy with AARS2 and MTO1. However, atypical clinical features were present in some patients, including normal liver function and Leigh syndrome (subacute necrotizing encephalomyelopathy) seen in association with TRMU mutations and no cardiomyopathy with founder SCO2 mutations. It was not possible to confidently identify the underlying genetic basis in 21 patients (40%; 95% CI, 26%-54%). Exome sequencing enhances the ability to identify potential nuclear gene mutations in patients with biochemically defined defects affecting multiple mitochondrial respiratory chain complexes. Additional study is required in independent patient populations to determine the utility of this approach in comparison with traditional diagnostic methods.

Opposite and tissue-specific effects of coenzyme Q2 on mPTP opening and ROS production between heart and liver mitochondria: role of complex I.

PubMed

Gharib, Abdallah; De Paulis, Damien; Li, Bo; Augeul, Lionel; Couture-Lepetit, Elisabeth; Gomez, Ludovic; Angoulvant, Denis; Ovize, Michel

2012-05-01

Coenzyme Q(2) (CoQ(2)) is known to inhibit mitochondrial permeability transition pore (mPTP) opening in isolated rat liver mitochondria. In this study, we investigated and compared the effects of CoQ(2) on mPTP opening and ROS production in isolated rabbit heart and rat liver mitochondria. Mitochondria were isolated from New Zealand White rabbit hearts and Wistar rat livers. Oxygen consumption, Ca(2+)-induced mPTP opening, ROS production and NADH DUb-reductase activity were measured. Rotenone was used to investigate the effect of CoQ(2) on respiratory complex I activity. CoQ(2) (23 μM) reduced the respiratory control index by 32% and 57% (p<0.01) in heart and liver mitochondria respectively, mainly through an increased oxygen consumption in state 4. CoQ(2) induced a 60% (p<0.05) decrease of calcium retention capacity (CRC) in heart mitochondria and inversely a 46% (p<0.05) increase in liver mitochondria. In basal condition, CoQ(2) induced a 170% (p<0.05) increase of H(2)O(2) production in heart mitochondria and 21% (ns) decrease of H(2)O(2) production in liver mitochondria. Because rotenone, a complex I inhibitor, increases H(2)O(2) production in heart but not in liver mitochondria we investigated the CoQ(2) effect in a dose-response assay of complex I inhibition by rotenone in both mitochondria. CoQ(2) antagonized the effect of rotenone on respiratory complex I activity in liver but not in heart mitochondria. CoQ(2) significantly reduced NADH DUb-reductase activity in liver (-47%) and heart (-37%) mitochondria. In conclusion, our data showed that on the contrary to what was observed in liver mitochondria, CoQ(2) favors mPTP opening and ROS production in heart mitochondria through an opposite effect on respiratory complex I activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Are point-of-care (POC) virological tests what is needed?

PubMed

Madeley, C R

2007-07-01

Point-of-care (POC) tests are becoming more available, although the way in which they should be used is currently undecided. Any 'laboratory'-based diagnosis of respiratory infections has three components: the specimen taken, the test used, and the interpretation of the results. Each of these components needs to be carefully addressed when using POC tests for the diagnosis of respiratory tract infections. Given the enthusiasm with which POC tests are being developed, it is likely that they will be used more and more widely. If so, the advantages and limitations of their use should be fully discussed and the implications recognised.

Health effects of subchronic inhalation exposure to gasoline engine exhaust.

PubMed

Reed, M D; Barrett, E G; Campen, M J; Divine, K K; Gigliotti, A P; McDonald, J D; Seagrave, J C; Mauderly, J L; Seilkop, S K; Swenberg, J A

2008-10-01

Gasoline engine emissions are a ubiquitous source of exposure to complex mixtures of particulate matter (PM) and non-PM pollutants; yet their health hazards have received little study in comparison with those of diesel emissions. As a component of the National Environmental Respiratory Center (NERC) multipollutant research program, F344 and SHR rats and A/J, C57BL/6, and BALBc mice were exposed 6 h/day, 7 days/week for 1 week to 6 months to exhaust from 1996 General Motors 4.3-L engines burning national average fuel on a simulated urban operating cycle. Exposure groups included whole exhaust diluted 1:10, 1:15, or 1:90, filtered exhaust at the 1:10 dilution, or clean air controls. Evaluations included organ weight, histopathology, hematology, serum chemistry, bronchoalveolar lavage, cardiac electrophysiology, micronuclei in circulating cells, DNA methylation and oxidative injury, clearance of Pseudomonas aeruginosa from the lung, and development of respiratory allergic responses to ovalbumin. Among the 120 outcome variables, only 20 demonstrated significant exposure effects. Several statistically significant effects appeared isolated and were not supported by related variables. The most coherent and consistent effects were those related to increased red blood cells, interpreted as likely to have resulted from exposure to 13-107 ppm carbon monoxide. Other effects supported by multiple variables included mild lung irritation and depression of oxidant production by alveolar macrophages. The lowest exposure level caused no significant effects. Because only 6 of the 20 significant effects appeared to be substantially reversed by PM filtration, the majority of effects were apparently caused by non-PM components of exhaust.

SU-F-J-138: An Extension of PCA-Based Respiratory Deformation Modeling Via Multi-Linear Decomposition

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

Iliopoulos, AS; Sun, X; Pitsianis, N

Purpose: To address and lift the limited degree of freedom (DoF) of globally bilinear motion components such as those based on principal components analysis (PCA), for encoding and modeling volumetric deformation motion. Methods: We provide a systematic approach to obtaining a multi-linear decomposition (MLD) and associated motion model from deformation vector field (DVF) data. We had previously introduced MLD for capturing multi-way relationships between DVF variables, without being restricted by the bilinear component format of PCA-based models. PCA-based modeling is commonly used for encoding patient-specific deformation as per planning 4D-CT images, and aiding on-board motion estimation during radiotherapy. However, themore » bilinear space-time decomposition inherently limits the DoF of such models by the small number of respiratory phases. While this limit is not reached in model studies using analytical or digital phantoms with low-rank motion, it compromises modeling power in the presence of relative motion, asymmetries and hysteresis, etc, which are often observed in patient data. Specifically, a low-DoF model will spuriously couple incoherent motion components, compromising its adaptability to on-board deformation changes. By the multi-linear format of extracted motion components, MLD-based models can encode higher-DoF deformation structure. Results: We conduct mathematical and experimental comparisons between PCA- and MLD-based models. A set of temporally-sampled analytical trajectories provides a synthetic, high-rank DVF; trajectories correspond to respiratory and cardiac motion factors, including different relative frequencies and spatial variations. Additionally, a digital XCAT phantom is used to simulate a lung lesion deforming incoherently with respect to the body, which adheres to a simple respiratory trend. In both cases, coupling of incoherent motion components due to a low model DoF is clearly demonstrated. Conclusion: Multi-linear decomposition can enable decoupling of distinct motion factors in high-rank DVF measurements. This may improve motion model expressiveness and adaptability to on-board deformation, aiding model-based image reconstruction for target verification. NIH Grant No. R01-184173.« less

Evidence for a respiratory component, similar to mammalian respiratory sinus arrhythmia, in the heart rate variability signal from the rattlesnake, Crotalus durissus terrificus.

PubMed

Campbell, Hamish A; Leite, Cleo A C; Wang, Tobias; Skals, Marianne; Abe, Augusto S; Egginton, Stuart; Rantin, F Tadeu; Bishop, Charles M; Taylor, Edwin W

2006-07-01

Autonomic control of heart rate variability and the central location of vagal preganglionic neurones (VPN) were examined in the rattlesnake (Crotalus durissus terrificus), in order to determine whether respiratory sinus arrhythmia (RSA) occurred in a similar manner to that described for mammals. Resting ECG signals were recorded in undisturbed snakes using miniature datalogging devices, and the presence of oscillations in heart rate (fh) was assessed by power spectral analysis (PSA). This mathematical technique provides a graphical output that enables the estimation of cardiac autonomic control by measuring periodic changes in the heart beat interval. At fh above 19 min(-1) spectra were mainly characterised by low frequency components, reflecting mainly adrenergic tonus on the heart. By contrast, at fh below 19 min(-1) spectra typically contained high frequency components, demonstrated to be cholinergic in origin. Snakes with a fh >19 min(-1) may therefore have insufficient cholinergic tonus and/or too high an adrenergic tonus acting upon the heart for respiratory sinus arrhythmia (RSA) to develop. A parallel study monitored fh simultaneously with the intraperitoneal pressures associated with lung inflation. Snakes with a fh<19 min(-1) exhibited a high frequency (HF) peak in the power spectrum, which correlated with ventilation rate (fv). Adrenergic blockade by propranolol infusion increased the variability of the ventilation cycle, and the oscillatory component of the fh spectrum broadened accordingly. Infusion of atropine to effect cholinergic blockade abolished this HF component, confirming a role for vagal control of the heart in matching fh and fv in the rattlesnake. A neuroanatomical study of the brainstem revealed two locations for vagal preganglionic neurones (VPN). This is consistent with the suggestion that generation of ventilatory components in the heart rate variability (HRV) signal are dependent on spatially distinct loci for cardiac VPN. Therefore, this study has demonstrated the presence of RSA in the HRV signal and a dual location for VPN in the rattlesnake. We suggest there to be a causal relationship between these two observations.

Do respiratory therapists receive training and education in smoking cessation? A national study of post-secondary training programs.

PubMed

Jordan, Timothy R; Khubchandani, Jagdish; Wiblishauser, Michael; Glassman, Tavis; Thompson, Amy

2011-10-01

To assess the tobacco-related education provided by post-secondary respiratory therapy training programs in the United States. A cross-sectional research design was used to survey the entire population of program directors of post-secondary, respiratory therapy training programs in the United States. A valid and reliable questionnaire was developed and mailed using a 2-wave mailing technique (73% return rate). Internal reliability coefficients (Cronbach alpha) for the various components of the questionnaire ranged from 0.78 to 0.91. More than half of programs (56%) offered no teaching on the 5R's. Nearly half (47%) offered no teaching on the 5A's. Of the 13 tobacco-related topics listed in the basic science and clinical science sections of the questionnaire, only one topic (i.e., diseases linked to tobacco use) received 3h or more of instruction by approximately a third of programs (35.8%). The majority of programs (>90%) spent no time teaching students about the socio-political aspects of tobacco use cessation. Moreover, 41% of programs did not formally evaluate students' competence in providing smoking cessation counseling to patients. Tobacco-related education is a very minor component of the education and training received by respiratory therapy students in the United States. Respiratory therapy training programs in the United States have great potential to strengthen the tobacco-related education that they provide to students. Practicing respiratory therapists would likely benefit from continuing medical education focused on how to use evidence-based smoking cessation counseling techniques with patients. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Respiratory processes in non-photosynthetic plastids

PubMed Central

Renato, Marta; Boronat, Albert; Azcón-Bieto, Joaquín

2015-01-01

Chlororespiration is a respiratory process located in chloroplast thylakoids which consists in an electron transport chain from NAD(P)H to oxygen. This respiratory chain involves the NAD(P)H dehydrogenase complex, the plastoquinone pool and the plastid terminal oxidase (PTOX), and it probably acts as a safety valve to prevent the over-reduction of the photosynthetic machinery in stress conditions. The existence of a similar respiratory activity in non-photosynthetic plastids has been less studied. Recently, it has been reported that tomato fruit chromoplasts present an oxygen consumption activity linked to ATP synthesis. Etioplasts and amyloplasts contain several electron carriers and some subunits of the ATP synthase, so they could harbor a similar respiratory process. This review provides an update on the study about respiratory processes in chromoplasts, identifying the major gaps that need to be addressed in future research. It also reviews the proteomic data of etioplasts and amyloplasts, which suggest the presence of a respiratory electron transport chain in these plastids. PMID:26236317

A serological investigation of the thirty-year history of exposure to Mycoplasma bovis in healthy North American bison

USDA-ARS?s Scientific Manuscript database

Mycoplasma bovis causes mastitis, pneumonia and arthritis in cattle and is a major contributor to bovine respiratory disease complex. Recently, it has emerged as a significant respiratory and reproductive health problem in bison. Understanding why M. bovis, known to cause disease in cattle for ove...

Respiratory Patterns and Strategies during Feeding in Preterm Infants

ERIC Educational Resources Information Center

Vice, Frank L.; Gewolb, Ira H.

2008-01-01

Because patterns of integration of respiration into rhythmic suck-swallow efforts are highly variable, we examined the vagaries of respiratory efforts as they evolve from the first tentative attempts at integration through more complex rhythmic interactions, with a focus on several strategies in which breathing and suck-swallow are coordinated.…

Fluorescent tagging of rhythmically active respiratory neurons within the pre-Bötzinger complex of rat medullary slice preparations.

PubMed

Pagliardini, Silvia; Adachi, Tadafumi; Ren, Jun; Funk, Gregory D; Greer, John J

2005-03-09

Elucidation of the neuronal mechanisms underlying respiratory rhythmogenesis is a major focal point in respiratory physiology. An area of the ventrolateral medulla, the pre-Bötzinger complex (preBotC), is a critical site. Attention is now focused on understanding the cellular and network properties within the preBotC that underlie this critical function. The inability to clearly identify key "rhythm-generating" neurons within the heterogeneous population of preBotC neurons has been a significant limitation. Here we report an advancement allowing precise targeting of neurons expressing neurokinin-1 receptors (NK1Rs), which are hypothesized to be essential for respiratory rhythmogenesis. The internalization of tetramethylrhodamine conjugated substance P in rhythmically active medullary slice preparations provided clear visualization of NK1R-expressing neurons for subsequent whole-cell patch-clamp recordings. Among labeled neurons, 82% were inspiratory modulated, and 25% had pacemaker properties. We propose that this approach can be used to greatly expedite progress toward understanding the neuronal processes underlying the control of breathing.

[Hospital management of acute respiratory failure: the role of the pulmonologist and of the respiratory intensive care unit].

PubMed

Scala, Raffaele

2009-04-01

Acute respiratory failure (ARF) is one of the most common and severe urgencies of the modern medicine which may require the application of mechanical ventilation and a careful monitoring of the patient's conditions. With the popularity of non-invasive ventilation and the interest of the pulmonologist for the care of the respiratory critical patient, in Italy there has been the spreading of Respiratory Intensive Care Units (RICU), which are as intermediate specialist structures in terms of intensity of care between the General Intensive Care Unit and the ordinary ward. In this article, the author analysed the cultural, scientific and organizational aspects of the central role played by the pulmonologist who's working in the RICU in the complex intra-hospital multi-disciplinary management of ARF.

Depletion of substance P and glutamate by capsaicin blocks respiratory rhythm in neonatal rat in vitro

PubMed Central

Morgado-Valle, Consuelo; Feldman, Jack L

2004-01-01

The specific role of the neuromodulator substance P (SP) and its target, the neurokinin 1 receptor (NK1R), in the generation and regulation of respiratory activity is not known. The preBötzinger complex (preBötC), an essential site for respiratory rhythm generation, contains glutamatergic NK1R-expressing neurones that are strongly modulated by exogenously applied SP or acute pharmacological blockade of NK1Rs. We investigated the effects of capsaicin, which depletes neuropeptides (including SP) and glutamate from presynaptic terminals, on respiratory motor output in medullary slice preparations of neonatal rat that generate respiratory-related activity. Bath application of capsaicin slowed respiratory motor output in a dose- and time-dependent manner. Respiratory rhythm could be restored by bath application of SP or glutamate transporter blockers. Capsaicin also evoked dose-dependent glutamate release and depleted SP in fibres within the preBötC. Our results suggest that depletion of SP (or other peptides) and/or glutamate by capsaicin causes a cessation of respiratory rhythm in neonatal rat slices. PMID:14724197

Depletion of substance P and glutamate by capsaicin blocks respiratory rhythm in neonatal rat in vitro.

PubMed

Morgado-Valle, Consuelo; Feldman, Jack L

2004-03-16

The specific role of the neuromodulator substance P (SP) and its target, the neurokinin 1 receptor (NK1R), in the generation and regulation of respiratory activity is not known. The preBötzinger complex (preBötC), an essential site for respiratory rhythm generation, contains glutamatergic NK1R-expressing neurones that are strongly modulated by exogenously applied SP or acute pharmacological blockade of NK1Rs. We investigated the effects of capsaicin, which depletes neuropeptides (including SP) and glutamate from presynaptic terminals, on respiratory motor output in medullary slice preparations of neonatal rat that generate respiratory-related activity. Bath application of capsaicin slowed respiratory motor output in a dose- and time-dependent manner. Respiratory rhythm could be restored by bath application of SP or glutamate transporter blockers. Capsaicin also evoked dose-dependent glutamate release and depleted SP in fibres within the preBötC. Our results suggest that depletion of SP (or other peptides) and/or glutamate by capsaicin causes a cessation of respiratory rhythm in neonatal rat slices.

The Rieske Iron-Sulfur Protein: Import and Assembly into the Cytochrome bc(1) Complex of Yeast Mitochondria.

PubMed

Conte, Laura; Zara, Vincenzo

2011-01-01

The Rieske iron-sulfur protein, one of the catalytic subunits of the cytochrome bc(1) complex, is involved in electron transfer at the level of the inner membrane of yeast mitochondria. The Rieske iron-sulfur protein is encoded by nuclear DNA and, after being synthesized in the cytosol, is imported into mitochondria with the help of a cleavable N-terminal presequence. The imported protein, besides incorporating the 2Fe-2S cluster, also interacts with other catalytic and non-catalytic subunits of the cytochrome bc(1) complex, thereby assembling into the mature and functional respiratory complex. In this paper, we summarize the most recent findings on the import and assembly of the Rieske iron-sulfur protein into Saccharomyces cerevisiae mitochondria, also discussing a possible role of this protein both in the dimerization of the cytochrome bc(1) complex and in the interaction of this homodimer with other complexes of the mitochondrial respiratory chain.

The Rieske Iron-Sulfur Protein: Import and Assembly into the Cytochrome bc 1 Complex of Yeast Mitochondria

PubMed Central

Conte, Laura; Zara, Vincenzo

2011-01-01

The Rieske iron-sulfur protein, one of the catalytic subunits of the cytochrome bc 1 complex, is involved in electron transfer at the level of the inner membrane of yeast mitochondria. The Rieske iron-sulfur protein is encoded by nuclear DNA and, after being synthesized in the cytosol, is imported into mitochondria with the help of a cleavable N-terminal presequence. The imported protein, besides incorporating the 2Fe-2S cluster, also interacts with other catalytic and non-catalytic subunits of the cytochrome bc 1 complex, thereby assembling into the mature and functional respiratory complex. In this paper, we summarize the most recent findings on the import and assembly of the Rieske iron-sulfur protein into Saccharomyces cerevisiae mitochondria, also discussing a possible role of this protein both in the dimerization of the cytochrome bc 1 complex and in the interaction of this homodimer with other complexes of the mitochondrial respiratory chain. PMID:21716720

Bursting Transition Dynamics Within the Pre-Bötzinger Complex

NASA Astrophysics Data System (ADS)

Duan, Lixia; Chen, Xi; Tang, Xuhui; Su, Jianzhong

The pre-Bötzinger complex of the mammalian brain stem plays a crucial role in the respiratory rhythms generation. Neurons within the pre-Bötzinger complex have been found experimentally to yield different firing activities. In this paper, we study the spiking and bursting activities related to the respiratory rhythms in the pre-Bötzinger complex based on a mathematical model proposed by Butera. Using the one-dimensional first recurrence map induced by dynamics, we investigate the different bursting patterns and their transition of the pre-Bötzinger complex neurons based on the Butera model, after we derived a one-dimensional map from the dynamical characters of the differential equations, and we obtained conditions for the transition of different bursting patterns. These analytical results were verified through numerical simulations. We conclude that the one-dimensional map contains similar rhythmic patterns as the Butera model and can be used as a simpler modeling tool to study fast-slow models like pre-Bötzinger complex neural circuit.

The aerobic respiratory chain of the acidophilic archaeon Ferroplasma acidiphilum: A membrane-bound complex oxidizing ferrous iron.

PubMed

Castelle, Cindy J; Roger, Magali; Bauzan, Marielle; Brugna, Myriam; Lignon, Sabrina; Nimtz, Manfred; Golyshina, Olga V; Giudici-Orticoni, Marie-Thérèse; Guiral, Marianne

2015-08-01

The extremely acidophilic archaeon Ferroplasma acidiphilum is found in iron-rich biomining environments and is an important micro-organism in naturally occurring microbial communities in acid mine drainage. F. acidiphilum is an iron oxidizer that belongs to the order Thermoplasmatales (Euryarchaeota), which harbors the most extremely acidophilic micro-organisms known so far. At present, little is known about the nature or the structural and functional organization of the proteins in F. acidiphilum that impact the iron biogeochemical cycle. We combine here biochemical and biophysical techniques such as enzyme purification, activity measurements, proteomics and spectroscopy to characterize the iron oxidation pathway(s) in F. acidiphilum. We isolated two respiratory membrane protein complexes: a 850 kDa complex containing an aa3-type cytochrome oxidase and a blue copper protein, which directly oxidizes ferrous iron and reduces molecular oxygen, and a 150 kDa cytochrome ba complex likely composed of a di-heme cytochrome and a Rieske protein. We tentatively propose that both of these complexes are involved in iron oxidation respiratory chains, functioning in the so-called uphill and downhill electron flow pathways, consistent with autotrophic life. The cytochrome ba complex could possibly play a role in regenerating reducing equivalents by a reverse ('uphill') electron flow. This study constitutes the first detailed biochemical investigation of the metalloproteins that are potentially directly involved in iron-mediated energy conservation in a member of the acidophilic archaea of the genus Ferroplasma. Copyright © 2015 Elsevier B.V. All rights reserved.

A combined technique using a muscular flap and endobronchial stent to repair complex broncho-oesophageal fistulae supported by ECMO.

PubMed

Baste, Jean-Marc; Haddad, Laura; Philouze, Guillaume

2018-02-01

Certain broncho-oesophageal fistulae require surgical repair. Herein, we describe an innovative surgical technique combining intercostal flap and endobronchial stenting. Two patients, each with a with complex broncho-oesophageal fistula 2 years after radio-chemotherapy, were hospitalised for severe respiratory infection and extension of the fistula despite previous endoscopic treatment. The first patient presented with respiratory distress (ARDS). She had emergency surgery under extra corporeal membrane oxygenation: oesophagectomy and reconstruction of the left bronchus by a vascularised intercostal flap. Stenting was performed on day 10, due to persistence of the fistula. At 3 months the bronchus was healed, but the patient died of cerebral bleeding. For the second patient, repair was proposed before severe ARDS with the same surgical and ventilatory strategy and a stent was preventively inserted after surgery. After 3 months, the stent was removed and the left bronchus was healed. Complex post-radiotherapy broncho-oesophageal fistulae should be treated surgically before respiratory complications arise, by combining reconstruction with a vascularised flap and transient stenting.

Deficiency of PHB complex impairs respiratory supercomplex formation and activates mitochondrial flashes.

PubMed

Jian, Chongshu; Xu, Fengli; Hou, Tingting; Sun, Tao; Li, Jinghang; Cheng, Heping; Wang, Xianhua

2017-08-01

Prohibitins (PHBs; prohibitin 1, PHB1 or PHB, and prohibitin 2, PHB2) are evolutionarily conserved and ubiquitously expressed mitochondrial proteins. PHBs form multimeric ring complexes acting as scaffolds in the inner mitochondrial membrane. Mitochondrial flashes (mitoflashes) are newly discovered mitochondrial signaling events that reflect electrical and chemical excitations of the organelle. Here, we investigate the possible roles of PHBs in the regulation of mitoflash signaling. Downregulation of PHBs increases mitoflash frequency by up to 5.4-fold due to elevated basal reactive oxygen species (ROS) production in the mitochondria. Mechanistically, PHB deficiency impairs the formation of mitochondrial respiratory supercomplexes (RSCs) without altering the abundance of individual respiratory complex subunits. These impairments induced by PHB deficiency are effectively rescued by co-expression of PHB1 and PHB2, indicating that the multimeric PHB complex acts as the functional unit. Furthermore, downregulating other RSC assembly factors, including SCAFI (also known as COX7A2L), RCF1a (HIGD1A), RCF1b (HIGD2A), UQCC3 and SLP2 (STOML2), all activate mitoflashes through elevating mitochondrial ROS production. Our findings identify the PHB complex as a new regulator of RSC formation and mitoflash signaling, and delineate a general relationship among RSC formation, basal ROS production and mitoflash biogenesis. © 2017. Published by The Company of Biologists Ltd.

Community based study to compare the incidence and health services utilization pyramid for gastrointestinal, respiratory and dermal symptoms.

PubMed

Najnin, Nusrat; Sinclair, Martha; Forbes, Andrew; Leder, Karin

2012-07-23

Gastrointestinal (GI), respiratory and dermal symptoms are common and cause substantial morbidity, although the information on their exact incidence and comparative burden is limited. The aim of this study was to describe the epidemiology and rate these three major symptom complexes in order to improve our understanding of the health burden imposed by these symptoms. We used data from a community based randomised control trial conducted from June 2007 to August 2008 among 277 South Australian families consuming rainwater. Using weekly health diaries, we prospectively collected information on GI (diarrhoea or vomiting), respiratory (sore throat, runny nose or cough) and dermal (rash, generalised itch or dermal infection) symptoms, as well as on relevant GP visits, time off work and/or hospitalisation due to these symptoms. Data were analysed using generalized estimating equations approach taking into account the variable number of weeks of follow-up of each individual and within-family clustering of responses. Over one year, at least one episode of GI symptoms was reported by 54% of participants (95% CI 50%-58%), at least one respiratory episode by 91% (95% CI 88%-93%) and at least one episode of dermal symptoms by 27% (95% CI 24%-30%). The average number of weeks per year during which respiratory symptoms occurred was four times greater than for GI or dermal symptoms (4.9, 1.2 and 1.2 weeks, respectively, p<0.001), with an average number of GP visits per person per year being twice as frequent (0.48, 0.26, 0.19 respectively, p<0.001). However, on a per episode basis, a higher proportion of people saw a GP or were hospitalised for GI symptoms. This first comparative study of three different symptom complexes showed that although respiratory symptoms are most common, GI symptoms cause a greater per episode burden on healthcare resources. Measuring and comparing the community based burden of these symptom complexes will assist evidence-based allocation of resources.

Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons

PubMed Central

Henry, Camille; Agrebi, Rym; Vergnes, Alexandra; Oheix, Emmanuel; Bos, Julia; Leverrier, Pauline; Espinosa, Leon; Szewczyk, Joanna; Vertommen, Didier; Iranzo, Olga; Collet, Jean-François; Barras, Frédéric

2015-01-01

The reactive species of oxygen (ROS) and chlorine (RCS) damage cellular components, potentially leading to cell death. In proteins, the sulfur-containing amino acid methionine (Met) is converted to methionine sulfoxide (Met-O), which can cause a loss of biological activity. To rescue proteins with Met-O residues, living cells express methionine sulfoxide reductases (Msrs) in most subcellular compartments, including the cytosol, mitochondria and chloroplasts 1-3. Here, we report the identification of an enzymatic system, MsrPQ, repairing Met-O containing proteins in the bacterial cell envelope, a compartment particularly exposed to the ROS and RCS generated by the host defense mechanisms. MsrP, a molybdo-enzyme, and MsrQ, a heme-binding membrane protein, are widely conserved throughout Gram-negative bacteria, including major human pathogens. MsrPQ synthesis is induced by hypochlorous acid (HOCl), a powerful antimicrobial released by neutrophils. Consistently, MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing a wide series of structurally unrelated periplasmic proteins from Met oxidation, including the primary periplasmic chaperone SurA. For this activity, MsrPQ uses electrons from the respiratory chain, which represents a novel mechanism to import reducing equivalents into the bacterial cell envelope. A remarkable feature of MsrPQ is its capacity to reduce both R- and S- diastereoisomers of Met-O, making this oxidoreductase complex functionally different from previously identified Msrs. The discovery that a large class of bacteria contain a single, non-stereospecific enzymatic complex fully protecting Met residues from oxidation should prompt search for similar systems in eukaryotic subcellular oxidizing compartments, including the endoplasmic reticulum (ER). PMID:26641313

Repairing oxidized proteins in the bacterial envelope using respiratory chain electrons.

PubMed

Gennaris, Alexandra; Ezraty, Benjamin; Henry, Camille; Agrebi, Rym; Vergnes, Alexandra; Oheix, Emmanuel; Bos, Julia; Leverrier, Pauline; Espinosa, Leon; Szewczyk, Joanna; Vertommen, Didier; Iranzo, Olga; Collet, Jean-François; Barras, Frédéric

2015-12-17

The reactive species of oxygen and chlorine damage cellular components, potentially leading to cell death. In proteins, the sulfur-containing amino acid methionine is converted to methionine sulfoxide, which can cause a loss of biological activity. To rescue proteins with methionine sulfoxide residues, living cells express methionine sulfoxide reductases (Msrs) in most subcellular compartments, including the cytosol, mitochondria and chloroplasts. Here we report the identification of an enzymatic system, MsrPQ, repairing proteins containing methionine sulfoxide in the bacterial cell envelope, a compartment particularly exposed to the reactive species of oxygen and chlorine generated by the host defence mechanisms. MsrP, a molybdo-enzyme, and MsrQ, a haem-binding membrane protein, are widely conserved throughout Gram-negative bacteria, including major human pathogens. MsrPQ synthesis is induced by hypochlorous acid, a powerful antimicrobial released by neutrophils. Consistently, MsrPQ is essential for the maintenance of envelope integrity under bleach stress, rescuing a wide series of structurally unrelated periplasmic proteins from methionine oxidation, including the primary periplasmic chaperone SurA. For this activity, MsrPQ uses electrons from the respiratory chain, which represents a novel mechanism to import reducing equivalents into the bacterial cell envelope. A remarkable feature of MsrPQ is its capacity to reduce both rectus (R-) and sinister (S-) diastereoisomers of methionine sulfoxide, making this oxidoreductase complex functionally different from previously identified Msrs. The discovery that a large class of bacteria contain a single, non-stereospecific enzymatic complex fully protecting methionine residues from oxidation should prompt a search for similar systems in eukaryotic subcellular oxidizing compartments, including the endoplasmic reticulum.

Quantication and analysis of respiratory motion from 4D MRI

NASA Astrophysics Data System (ADS)

Aizzuddin Abd Rahni, Ashrani; Lewis, Emma; Wells, Kevin

2014-11-01

It is well known that respiratory motion affects image acquisition and also external beam radiotherapy (EBRT) treatment planning and delivery. However often the existing approaches for respiratory motion management are based on a generic view of respiratory motion such as the general movement of organ, tissue or fiducials. This paper thus aims to present a more in depth analysis of respiratory motion based on 4D MRI for further integration into motion correction in image acquisition or image based EBRT. Internal and external motion was first analysed separately, on a per-organ basis for internal motion. Principal component analysis (PCA) was then performed on the internal and external motion vectors separately and the relationship between the two PCA spaces was analysed. The motion extracted from 4D MRI on general was found to be consistent with what has been reported in literature.

Treating co-morbid chronic medical conditions and anxiety/depression.

PubMed

Cimpean, D; Drake, R E

2011-06-01

This systematic review examines interventions for care of people with co-morbid chronic medical illness and anxiety/depression disorders--a group with high risks for morbidity and mortality. Systematic search of Medline 1995 to January 2011 for randomized controlled trials of treatment interventions designed for adult outpatients with diagnosed chronic medical illness (diabetes mellitus, cardiovascular disorders, and chronic respiratory disorders) and anxiety/depression disorders. Six trials studied complex interventions based on the chronic care model, and eight trials studied psychosocial interventions. Most interventions addressed the mental health aspect of the co-morbidity and showed improvements in anxiety/depression but not in the co-morbid medical disorder. Further research might focus on interventions integrating mental health treatment with enhanced medical care components, incorporating shared-decision making and information technology advances.

Transcriptional regulation of respiration in yeast metabolizing differently repressive carbon substrates.

PubMed

Fendt, Sarah-Maria; Sauer, Uwe

2010-02-18

Depending on the carbon source, Saccharomyces cerevisiae displays various degrees of respiration. These range from complete respiration as in the case of ethanol, to almost complete fermentation, and thus very low degrees of respiration on glucose. While many key regulators are known for these extreme cases, we focus here on regulators that are relevant at intermediate levels of respiration. We address this question by linking the functional degree of respiration to transcriptional regulation via enzyme abundances. Specifically, we investigated aerobic batch cultures with the differently repressive carbon sources glucose, mannose, galactose and pyruvate. Based on 13C flux analysis, we found that the respiratory contribution to cellular energy production was largely absent on glucose and mannose, intermediate on galactose and highest on pyruvate. In vivo abundances of 40 respiratory enzymes were quantified by GFP-fusions under each condition. During growth on the partly and fully respired substrates galactose and pyruvate, several TCA cycle and respiratory chain enzymes were significantly up-regulated. From these enzyme levels and the known regulatory network structure, we determined the probability for a given transcription factor to cause the coordinated expression changes. The most probable transcription factors to regulate the different degrees of respiration were Gcr1p, Cat8p, the Rtg-proteins and the Hap-complex. For the latter three ones we confirmed their importance for respiration by quantifying the degree of respiration and biomass yields in the corresponding deletion strains. Cat8p is required for wild-type like respiration, independent of its known activation of gluconeogenic genes. The Rtg-proteins and the Hap-complex are essential for wild-type like respiration under partially respiratory conditions. Under fully respiratory conditions, the Hap-complex, but not the Rtg-proteins are essential for respiration.

Advance care planning for patients with chronic respiratory diseases: a systematic review of preferences and practices.

PubMed

Jabbarian, Lea J; Zwakman, Marieke; van der Heide, Agnes; Kars, Marijke C; Janssen, Daisy J A; van Delden, Johannes J; Rietjens, Judith A C; Korfage, Ida J

2018-03-01

Advance care planning (ACP) supports patients in identifying and documenting their preferences and timely discussing them with their relatives and healthcare professionals (HCPs). Since the British Thoracic Society encourages ACP in chronic respiratory disease, the objective was to systematically review ACP practice in chronic respiratory disease, attitudes of patients and HCPs and barriers and facilitators related to engagement in ACP. We systematically searched 12 electronic databases for empirical studies on ACP in adults with chronic respiratory diseases. Identified studies underwent full review and data extraction. Of 2509 studies, 21 were eligible: 10 were quantitative studies. Although a majority of patients was interested in engaging in ACP, ACP was rarely carried out. Many HCPs acknowledged the importance of ACP but were hesitant to initiate it. Barriers to engagement in ACP were the complex disease course of patients with chronic respiratory diseases, HCPs' concern of taking away patients' hopes and lack of continuity of care. The identification of trigger points and training of HCPs on how to communicate sensitive topics were identified as facilitators to engagement in ACP. In conclusion, ACP is surprisingly uncommon in chronic respiratory disease, possibly due to the complex disease course of chronic respiratory diseases and ambivalence of both patients and HCPs to engage in ACP. Providing patients with information about their disease can help meeting their needs. Additionally, support of HCPs through identification of trigger points, training and system-related changes can facilitate engagement in ACP. CRD42016039787. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinical evaluation of the Abbott RealTime MTB Assay for direct detection of Mycobacterium tuberculosis-complex from respiratory and non-respiratory samples.

PubMed

Hinić, Vladimira; Feuz, Kinga; Turan, Selda; Berini, Andrea; Frei, Reno; Pfeifer, Karin; Goldenberger, Daniel

2017-05-01

Rapid and reliable diagnosis is crucial for correct management of tuberculosis. The Abbott RealTime MTB Assay represents a novel qualitative real-time PCR assay for direct detection of M. tuberculosis-complex (MTB) DNA from respiratory samples. The test targets two highly conserved sequences, the multi-copy insertion element IS6110 and the protein antigen B (PAB) gene of MTB, allowing even the detection of IS6610-deficient strains. We evaluated this commercial diagnostic test by analyzing 200 respiratory and, for the first time, 87 non-respiratory clinical specimens from our tertiary care institution and compared its results to our IS6110-based in-house real-time PCR for MTB as well as MTB culture. Overall sensitivity for Abbott RealTime MTB was 100% (19/19) in smear positive and 87.5% (7/8) in smear negative specimens, while the specificity of the assay was 100% (260/260). For both non-respiratory smear positive and smear negative specimens Abbott RealTime MTB tests showed 100% (8/8) sensitivity and 100% (8/8) specificity. Cycle threshold (Ct) value analysis of 16 MTB positive samples showed a slightly higher Ct value of the Abbott RealTime MTB test compared to our in-house MTB assay (mean delta Ct = 2.55). In conclusion, the performance of the new Abbott RealTime MTB Assay was highly similar to culture and in-house MTB PCR. We document successful analysis of 87 non-respiratory samples with the highly automated Abbott RealTime MTB test with no inhibition observed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deposition of naphthalene and tetradecane vapors in models of the human respiratory system.

PubMed

Zhang, Zhe; Kleinstreuer, Clement

2011-01-01

Jet-propulsion fuel (particularly JP-8) is currently being used worldwide, exposing especially Air Force personnel and people living near airfields to JP-8 vapors and aerosols during aircraft fueling, maintenance operations, and/or cold starts. JP-8 is a complex mixture containing >200, mostly toxic, aliphatic and aromatic hydrocarbon compounds of which tetradecane and naphthalene were chosen as two representative chemical markers for computer simulations. Thus, transport and deposition of naphthalene and tetradecane vapors have been simulated in models of the human respiratory system. The inspiratory deposition data were analyzed in terms of regional deposition fractions (DFs) and deposition enhancement factors (DEF). The vapor depositions are affected by vapor properties (e.g. diffusivity), airway geometric features, breathing patterns, inspiratory flow rates, as well as airway-wall absorption parameter. Specifically, the respiratory uptake of vapors is greatly influenced by the degree of airway-wall absorption. For example, being an almost insoluble species in the mucus layer, the deposition of tetradecane vapor is nearly zero in the extrathoracic and tracheobronchial (TB) airways, that is, the DF is <1%. The remaining vapors may penetrate further and deposit in the alveolar airways. The DF of tetradecane vapors during inhalation in the alveolar region can range from 7% to 24%, depending on breathing waveform, inhalation rate, and thickness of the mucus layer. In contrast, naphthalene vapor almost completely deposits in the extrathoracic and TB airways and hardly moves downstream and deposits in the respiratory zone. The DFs of naphthalene vapor in the extrathoracic airways from nasal/oral to trachea under normal breathing conditions (Q = 15-60 L/min) are about 12-34%, although they are about 66-87% in the TB airways. In addition, the variation of breathing routes (say, from nasal breathing to oral breathing) may influence the vapor deposition in the regions of nasal and oral cavities, nasopharynx and oropharynx, but hardly affects the deposition at and beyond the larynx. The different deposition patterns of naphthalene and tetradecane vapors in the human respiratory system may indicate different toxic and hence health effects of these toxic jet-fuel components.

Spectacularly robust! Tensegrity principle explains the mechanical strength of the avian lung.

PubMed

Maina, J N

2007-01-15

Among the air-breathing vertebrates, the respiratory system of birds, the lung-air sac system, is remarkably complex and singularly efficient. The most perplexing structural property of the avian lung pertains to its exceptional mechanical strength, especially that of the minuscule terminal respiratory units, the air- and the blood capillaries. In different species of birds, the air capillaries range in diameter from 3 to 20 micro m: the blood capillaries are in all cases relatively smaller. Over and above their capacity to withstand enormous surface tension forces at the air-tissue interface, the air capillaries resist mechanical compression (parabronchial distending pressure) as high as 20 cm H(2)O (2 kPa). The blood capillaries tolerate a pulmonary arterial vascular pressure of 24.1 mmHg (3.2 kPa) and vascular resistance of 22.5 mmHg (3 kPa) without distending. The design of the avian respiratory system fundamentally stems from the rigidity (strength) of the lung. The gas exchanger (the lung) is uncoupled from the ventilator (the air sacs), allowing the lung (the paleopulmonic parabronchi) to be ventilated continuously and unidirectionally by synchronized bellows like action of the air sacs. Since during the ventilation of the lung the air capillaries do not have to be distended (dilated), i.e., surface tension force does not have to be overcome (as would be the case if the lung was compliant), extremely intense subdivision of the exchange tissue was possible. Minuscule terminal respiratory units developed, producing a vast respiratory surface area in a limited lung volume. I make a case that a firm (rigid) rib cage, a lung tightly held by the ribs and the horizontal septum, a lung directly attached to the trunk, specially formed and compactly arranged parabronchi, intertwined atrial muscles, and tightly set air capillaries and blood capillaries form an integrated hierarchy of discrete network system of tension and compression, a tensegrity (tensional integrity) array, which absorbs, transmits, and dissipates stress, stabilizing (strengthening) the lung and its various structural components.

Morphometric analysis of astrocytes in brainstem respiratory regions.

PubMed

Sheikhbahaei, Shahriar; Morris, Brian; Collina, Jared; Anjum, Sommer; Znati, Sami; Gamarra, Julio; Zhang, Ruli; Gourine, Alexander V; Smith, Jeffrey C

2018-06-11

Astrocytes, the most abundant and structurally complex glial cells of the central nervous system, are proposed to play an important role in modulating the activities of neuronal networks, including respiratory rhythm-generating circuits of the preBötzinger complex (preBötC) located in the ventrolateral medulla of the brainstem. However, structural properties of astrocytes residing within different brainstem regions are unknown. In this study astrocytes in the preBötC, an intermediate reticular formation (IRF) region with respiratory-related function, and a region of the nucleus tractus solitarius (NTS) in adult rats were reconstructed and their morphological features were compared. Detailed morphological analysis revealed that preBötC astrocytes are structurally more complex than those residing within the functionally distinct neighboring IRF region, or the NTS, located at the dorsal aspect of the medulla oblongata. Structural analyses of the brainstem microvasculature indicated no significant regional differences in vascular properties. We hypothesize that high morphological complexity of preBötC astrocytes reflects their functional role in providing structural/metabolic support and modulation of the key neuronal circuits essential for breathing, as well as constraints imposed by arrangements of associated neurons and/or other local structural features of the brainstem parenchyma. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Cardiolipin deficiency causes a dissociation of the b 6 c:caa 3 megacomplex in B. subtilis membranes.

PubMed

García Montes de Oca, Led Yered Jafet; Cabellos Avelar, Tecilli; Picón Garrido, Gerardo Ignacio; Chagoya-López, Alicia; González de la Vara, Luis; Delgado Buenrostro, Norma Laura; Chirino-López, Yolanda Irasema; Gómez-Lojero, Carlos; Gutiérrez-Cirlos, Emma Berta

2016-08-01

The associations among respiratory complexes in energy-transducing membranes have been established. In fact, it is known that the Gram-negative bacteria Paracoccus denitrificans and Escherichia coli have respiratory supercomplexes in their membranes. These supercomplexes are important for channeling substrates between enzymes in a metabolic pathway, and the assembly of these supercomplexes depends on the protein subunits and membrane lipids, mainly cardiolipin, which is present in both the mitochondrial inner membrane and bacterial membranes. The Gram-positive bacterium Bacillus subtilis has a branched respiratory chain, in which some complexes generate proton motive force whereas others constitute an escape valve of excess reducing power. Some peculiarities of this respiratory chain are the following: a type II NADH dehydrogenase, a unique b 6 c complex that has a b 6 type cytochrome with a covalently bound heme, and a c-type heme attached to the third subunit, which is similar to subunit IV of the photosynthetic b 6 f complex. Cytochrome c oxygen reductase (caa 3 ) contains a c-type cytochrome on subunit I. We previously showed that the b 6 c and the caa 3 complexes form a supercomplex. Both the b 6 c and the caa 3 together with the quinol oxygen reductase aa 3 generate the proton motive force in B. subtilis. In order to seek proof that this supercomplex is important for bacterial growth in aerobic conditions we compared the b 6 c: caa 3 supercomplex from wild type membranes with membranes from two mutants lacking cardiolipin. Both mutant complexes were found to have similar activity and heme content as the wild type. Clear native electrophoresis showed that mutants lacking cardiolipin had b 6 c:caa 3 supercomplexes of lower mass or even individual complexes after membrane solubilization with digitonin. The use of dodecyl maltoside revealed a more evident difference between wild-type and mutant supercomplexes. Here we provide evidence showing that cardiolipin plays a role in the stability of the b 6 c:caa 3 supercomplex in B. subtilis.

Respiratory infections due to nontuberculous mycobacterias.

PubMed

Máiz Carro, Luis; Barbero Herranz, Esther; Nieto Royo, Rosa

2018-03-09

The most common infections caused by nontuberculous mycobacteria (NTM) are lung infections. The microorganisms causing these infections most frequently are Mycobacterium avium complex, Mycobacterium kansasii and Mycobacterium abscessus complex. Their incidence has increased in the last three decades. After identifying an NTM in the respiratory tract, clinical and radiological aspects must be considered to determine if isolations are clinically relevant. Predisposing conditions that could contribute to infection must also be investigated. Pulmonary disease due to NTM is presented in three clinical forms: a) pneumonitis due to hypersensitivity; b) fibrocavitary form; and c) nodular-bronchiectasic. The diagnosis of respiratory disease due to NTM does not make it obligatory to immediately initiate treatment. Before initiating the latter, other factors must be considered, such as age, comorbidities, life expectancy, due to the prolonged nature of treatments, with potential side effects and, in many cases, only a slight response to the treatment. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

An approach for evaluating the respiratory irritation of mixtures: application to metalworking fluids.

PubMed

Schaper, M M; Detwiler-Okabayashi, K A

1995-01-01

Recently, the sensory and pulmonary irritating properties of ten metalworking fluids (MWF) were assessed using a mouse bioassay. Relative potency of the MWFs was estimated, but it was not possible to identify the component(s) responsible for the the respiratory irritation induced by each MWF. One of the ten fluids, MWF "ET", produced sensory and pulmonary irritation in mice, and it was of moderate potency in comparison to the other nine MWFs. MWF "E" had three major components: tall oil fatty acids (TOFA), sodium sulfonate (SA), and paraffinic oil (PO). In the present study, the sensory and pulmonary irritating properties of these individual components of MWF "E" were evaluated. Mixtures of the three components were also prepared and similarly evaluated. This analysis revealed that the sensory irritation from MWF "E" was largely due to TOFA, whereas SA produced the pulmonary irritation observed with MWF "E". Both TOFA and SA were more potent irritants than was MWF "E", and the potency of TOFA and/or SA was diminished through combination with PO. There was no evidence of synergism of the components when combined to form MWF "E". This approach for identifying the biologically "active" component(s) in a mixture should be useful for other MWFs. Furthermore, the approach should be easily adapted for other applications involving concerns with mixtures.

Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

USDA-ARS?s Scientific Manuscript database

Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

Identification and genome characterization of genotype B and genotype C bovine parainfluenza type 3 viruses isolated in the United States

USDA-ARS?s Scientific Manuscript database

Background: Bovine parainfluenza 3 viruses (BPI3V) are respiratory pathogens of cattle that cause disease singly but are often associated with bovine respiratory disease complex (BRDC) in conjunction with other viral and bacterial agents. Bovine vaccines currently contain BPI3V to provide protection...

42 CFR 84.1131 - Respirators; required components.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Respirators; required components. 84.1131 Section 84.1131 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Dust, Fume...

42 CFR 84.1131 - Respirators; required components.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Respirators; required components. 84.1131 Section 84.1131 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Dust, Fume...

42 CFR 84.1131 - Respirators; required components.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Respirators; required components. 84.1131 Section 84.1131 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Dust, Fume...

42 CFR 84.1131 - Respirators; required components.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Respirators; required components. 84.1131 Section 84.1131 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Dust, Fume...

42 CFR 84.1131 - Respirators; required components.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Respirators; required components. 84.1131 Section 84.1131 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Dust, Fume...

Streptomycetes in house dust: associations with housing characteristics and endotoxin

EPA Science Inventory

In addition to mold, indoor bioaerosols also contain bacterial components that may have implications for human health. Endotoxin is a cell wall component in Gram-negative bacteria present at varying levels indoors that has been found to have respiratory health implications. Stre...

42 CFR 84.62 - Component parts; minimum requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Component parts; minimum requirements. 84.62 Section 84.62 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES General...

42 CFR 84.62 - Component parts; minimum requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Component parts; minimum requirements. 84.62 Section 84.62 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES General...

42 CFR 84.62 - Component parts; minimum requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Component parts; minimum requirements. 84.62 Section 84.62 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES General...

42 CFR 84.62 - Component parts; minimum requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Component parts; minimum requirements. 84.62 Section 84.62 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES General...

42 CFR 84.62 - Component parts; minimum requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Component parts; minimum requirements. 84.62 Section 84.62 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES General...

The pragmatics of feeding the pediatric patient with acute respiratory distress syndrome.

PubMed

Verger, Judy T; Bradshaw, Darla J; Henry, Elizabeth; Roberts, Kathryn E

2004-09-01

Acute respiratory distress syndrome (ARDS) represents the ultimate pulmonary response to a wide range of injuries, from septicemia to trauma. Optimal nutrition is vital to enhancing oxygen delivery, supporting adequate cardiac contractility and respiratory musculature, eliminating fluid and electrolyte imbalances, and supporting the proinflammatory response. Research is providing a better understanding of nutrients that specifically address the complex physiologic changes in ARDS. This article highlights the pathophysiology of ARDS as it relates to nutrition, relevant nutritional assessment, and important enteral and parenteral considerations for the pediatric patient who has ARDS.

Rapid screening for nuclear genes mutations in isolated respiratory chain complex I defects.

PubMed

Pagniez-Mammeri, Hélène; Lombes, Anne; Brivet, Michèle; Ogier-de Baulny, Hélène; Landrieu, Pierre; Legrand, Alain; Slama, Abdelhamid

2009-04-01

Complex I or reduced nicotinamide adenine dinucleotide (NADH): ubiquinone oxydoreductase deficiency is the most common cause of respiratory chain defects. Molecular bases of complex I deficiencies are rarely identified because of the dual genetic origin of this multi-enzymatic complex (nuclear DNA and mitochondrial DNA) and the lack of phenotype-genotype correlation. We used a rapid method to screen patients with isolated complex I deficiencies for nuclear genes mutations by Surveyor nuclease digestion of cDNAs. Eight complex I nuclear genes, among the most frequently mutated (NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, NDUFS8, NDUFV1 and NDUFV2), were studied in 22 cDNA fragments spanning their coding sequences in 8 patients with a biochemically proved complex I deficiency. Single nucleotide polymorphisms and missense mutations were detected in 18.7% of the cDNA fragments by Surveyor nuclease treatment. Molecular defects were detected in 3 patients. Surveyor nuclease screening is a reliable method for genotyping nuclear complex I deficiencies, easy to interpret, and limits the number of sequence reactions. Its use will enhance the possibility of prenatal diagnosis and help us for a better understanding of complex I molecular defects.

Real-time electron transfer in respiratory complex I

PubMed Central

Verkhovskaya, Marina L.; Belevich, Nikolai; Euro, Liliya; Wikström, Mårten; Verkhovsky, Michael I.

2008-01-01

Electron transfer in complex I from Escherichia coli was investigated by an ultrafast freeze-quench approach. The reaction of complex I with NADH was stopped in the time domain from 90 μs to 8 ms and analyzed by electron paramagnetic resonance (EPR) spectroscopy at low temperatures. The data show that after binding of the first molecule of NADH, two electrons move via the FMN cofactor to the iron–sulfur (Fe/S) centers N1a and N2 with an apparent time constant of ≈90 μs, implying that these two centers should have the highest redox potential in the enzyme. The rate of reduction of center N2 (the last center in the electron transfer sequence) is close to that predicted by electron transfer theory, which argues for the absence of coupled proton transfer or conformational changes during electron transfer from FMN to N2. After fast reduction of N1a and N2, we observe a slow, ≈1-ms component of reduction of other Fe/S clusters. Because all elementary electron transfer rates between clusters are several orders of magnitude higher than this observed rate, we conclude that the millisecond component is limited by a single process corresponding to dissociation of the oxidized NAD+ molecule from its binding site, where it prevents entry of the next NADH molecule. Despite the presence of approximately one ubiquinone per enzyme molecule, no transient semiquinone formation was observed, which has mechanistic implications, suggesting a high thermodynamic barrier for ubiquinone reduction to the semiquinone radical. Possible consequences of these findings for the proton translocation mechanism are discussed. PMID:18316732

Independent prognostic importance of respiratory instability and sympathetic nerve activity in patients with chronic heart failure.

PubMed

Asanoi, Hidetsugu; Harada, Daisuke; Oda, Yoshitaka; Ueno, Hiroshi; Takagawa, Junya; Ishise, Hisanari; Goso, Yukiko; Joho, Shuji; Inoue, Hiroshi

2017-11-01

Respiratory instability in chronic heart failure (CHF) is characterized by irregularly rapid respiration or non-periodic breathing rather than by Cheyne-Stokes respiration. We developed a new quantitative measure of respiratory instability (RSI) and examined its independent prognostic impact upon CHF. In 87 patients with stable CHF, respiratory flow and muscle sympathetic nerve activity (MSNA) were simultaneously recorded. RSI was calculated from the frequency distribution of respiratory spectral components and very low frequency components. During a mean follow-up of 85±38 months, 24 patients died. Sixteen patients who died of cardiac causes had a lower RSI (16±6 vs. 30±21, p<0.01), a lower specific activity scale (4.3±1.4 Mets vs. 5.7±1.4 Mets, p<0.005), a higher MSNA burst area (16±5% vs. 11±4%, p<0.001), and a higher brain natriuretic peptide (BNP) level (514±559pg/ml vs. 234±311pg/ml, p<0.05) than 71 patients who did not die of cardiac causes. Multivariate analysis revealed that RSI (p=0.015), followed by MSNA burst area (p=0.033), was an independent predictor of subsequent all-cause deaths and that RSI (p=0.026), MSNA burst area (p=0.001), and BNP (p=0.048) were independent predictors of cardiac deaths. Patients at very high risk of fatal outcome could be identified by an RSI<20. The daytime respiratory instability quantified by a new measure of RSI has prognostic importance independent of sympathetic nerve activation in patients with clinically stable CHF. An RSI of <20 identifies patients at very high risk for subsequent all-cause and cardiovascular death. Copyright © 2017. Published by Elsevier Ltd.

Breathing and Singing: Objective Characterization of Breathing Patterns in Classical Singers

PubMed Central

Salomoni, Sauro; van den Hoorn, Wolbert; Hodges, Paul

2016-01-01

Singing involves distinct respiratory kinematics (i.e. movements of rib cage and abdomen) to quiet breathing because of different demands on the respiratory system. Professional classical singers often advocate for the advantages of an active control of the abdomen on singing performance. This is presumed to prevent shortening of the diaphragm, elevate the rib cage, and thus promote efficient generation of subglottal pressure during phonation. However, few studies have investigated these patterns quantitatively and inter-subject variability has hindered the identification of stereotypical patterns of respiratory kinematics. Here, seven professional classical singers and four untrained individuals were assessed during quiet breathing, and when singing both a standard song and a piece of choice. Several parameters were extracted from respiratory kinematics and airflow, and principal component analysis was used to identify typical patterns of respiratory kinematics. No group differences were observed during quiet breathing. During singing, both groups adapted to rhythmical constraints with decreased time of inspiration and increased peak airflow. In contrast to untrained individuals, classical singers used greater percentage of abdominal contribution to lung volume during singing and greater asynchrony between movements of rib cage and abdomen. Classical singers substantially altered the coordination of rib cage and abdomen during singing from that used for quiet breathing. Despite variations between participants, principal component analysis revealed consistent pre-phonatory inward movements of the abdominal wall during singing. This contrasted with untrained individuals, who demonstrated synchronous respiratory movements during all tasks. The inward abdominal movements observed in classical singers elevates intra-abdominal pressure and may increase the length and the pressure-generating capacity of rib cage expiratory muscles for potential improvements in voice quality. PMID:27159498

Breathing and Singing: Objective Characterization of Breathing Patterns in Classical Singers.

PubMed

Salomoni, Sauro; van den Hoorn, Wolbert; Hodges, Paul

2016-01-01

Singing involves distinct respiratory kinematics (i.e. movements of rib cage and abdomen) to quiet breathing because of different demands on the respiratory system. Professional classical singers often advocate for the advantages of an active control of the abdomen on singing performance. This is presumed to prevent shortening of the diaphragm, elevate the rib cage, and thus promote efficient generation of subglottal pressure during phonation. However, few studies have investigated these patterns quantitatively and inter-subject variability has hindered the identification of stereotypical patterns of respiratory kinematics. Here, seven professional classical singers and four untrained individuals were assessed during quiet breathing, and when singing both a standard song and a piece of choice. Several parameters were extracted from respiratory kinematics and airflow, and principal component analysis was used to identify typical patterns of respiratory kinematics. No group differences were observed during quiet breathing. During singing, both groups adapted to rhythmical constraints with decreased time of inspiration and increased peak airflow. In contrast to untrained individuals, classical singers used greater percentage of abdominal contribution to lung volume during singing and greater asynchrony between movements of rib cage and abdomen. Classical singers substantially altered the coordination of rib cage and abdomen during singing from that used for quiet breathing. Despite variations between participants, principal component analysis revealed consistent pre-phonatory inward movements of the abdominal wall during singing. This contrasted with untrained individuals, who demonstrated synchronous respiratory movements during all tasks. The inward abdominal movements observed in classical singers elevates intra-abdominal pressure and may increase the length and the pressure-generating capacity of rib cage expiratory muscles for potential improvements in voice quality.

Time to consider the contact force during photoplethysmography measurement during pediatric anesthesia: A prospective, nonrandomized interventional study.

PubMed

Lee, Ji-Hyun; Yang, Seungman; Park, Jonghyun; Kim, Hee Chan; Kim, Eun-Hee; Jang, Young-Eun; Kim, Jin-Tae; Kim, Hee-Soo

2018-06-19

Respiratory variations in photoplethysmography amplitude enable volume status assessment. However, the contact force between the measurement site and sensor can affect photoplethysmography waveforms. We aimed to evaluate contact force effects on respiratory variations in photoplethysmography waveforms in children under general anesthesia. Children aged 3-5 years were enrolled. After anesthetic induction, mechanical ventilation commenced at a tidal volume of 10 mL/kg. Photoplethysmographic signals were obtained in the supine position from the index finger using a force sensor-integrated clip-type photoplethysmography sensor that increased the contact force from 0-1.4 N for 20 respiratory cycles at each force. The AC amplitude (pulsatile component), DC amplitude (nonpulsatile component), AC/DC ratio, and respiratory variations in photoplethysmography amplitude were calculated. Data from 34 children were analyzed. Seven contact forces at 0.2-N increments were evaluated for each patient. The normalized AC amplitude increased maximally at a contact force of 0.4-0.6 N and decreased with increasing contact force. However, the normalized DC amplitude increased with a contact force exceeding 0.4 N. ΔPOP decreased slightly and increased from the point when the AC amplitude started to decrease as contact force increased. In a 0.2-1.2 N contact force range, significant changes in the normalized AC amplitude, normalized DC amplitude, AC/DC ratio, and respiratory variations in photoplethysmography amplitude were observed. Respiratory variations in photoplethysmography amplitude changed according to variable contact forces; therefore, these measurements may not reflect respiration-induced stroke volume variations. Clinicians should consider contact force bias when interpreting morphological data from photoplethysmography signals. © 2018 John Wiley & Sons Ltd.

A structured approach to the study of metabolic control principles in intact and impaired mitochondria.

PubMed

Huber, Heinrich J; Connolly, Niamh M C; Dussmann, Heiko; Prehn, Jochen H M

2012-03-01

We devised an approach to extract control principles of cellular bioenergetics for intact and impaired mitochondria from ODE-based models and applied it to a recently established bioenergetic model of cancer cells. The approach used two methods for varying ODE model parameters to determine those model components that, either alone or in combination with other components, most decisively regulated bioenergetic state variables. We found that, while polarisation of the mitochondrial membrane potential (ΔΨ(m)) and, therefore, the protomotive force were critically determined by respiratory complex I activity in healthy mitochondria, complex III activity was dominant for ΔΨ(m) during conditions of cytochrome-c deficiency. As a further important result, cellular bioenergetics in healthy, ATP-producing mitochondria was regulated by three parameter clusters that describe (1) mitochondrial respiration, (2) ATP production and consumption and (3) coupling of ATP-production and respiration. These parameter clusters resembled metabolic blocks and their intermediaries from top-down control analyses. However, parameter clusters changed significantly when cells changed from low to high ATP levels or when mitochondria were considered to be impaired by loss of cytochrome-c. This change suggests that the assumption of static metabolic blocks by conventional top-down control analyses is not valid under these conditions. Our approach is complementary to both ODE and top-down control analysis approaches and allows a better insight into cellular bioenergetics and its pathological alterations.

Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer

DTIC Science & Technology

2011-05-01

Briefly, the electron transfer activities of complex I/III (NADH dehydrogenase/cytochrome bc1 complex: catalyzes the electron transfer from NADH to...ferricytochrome c) and complex II/III (succinate dehydrogenase/cytochrome bc1 complex: catalyzes the electron transfer from succinate to ferricytochrome...The electron transfer activity of complex IV (cytochrome c oxidase: catalyzes the final step of the respiratory chain by transferring electrons from

Respiratory health equality in the United States. The American thoracic society perspective.

PubMed

Celedón, Juan C; Roman, Jesse; Schraufnagel, Dean E; Thomas, Alvin; Samet, Jonathan

2014-05-01

Because the frequency of major risk factors for respiratory diseases (e.g., tobacco use) differs across demographic groups (defined by socioeconomic status, race/ethnicity, sexual orientation, health care access, occupation, or other characteristics), health disparities are commonly encountered in pediatric and adult pulmonary, critical care, and sleep medicine. As part of its policy on respiratory health disparities, the American Thoracic Society (ATS) Executive Committee created a Health Equality Subcommittee of the Health Policy Committee, with an initial mandate of defining respiratory health equality and, as a subsequent task, providing recommendations to the ATS leadership as to how our society may help attain such equality in the United States. After receiving input from the ATS assemblies and committees, the subcommittee developed this document on respiratory health equality. This document defines respiratory health disparities and respiratory health equality, and expands on a recent ATS and European Respiratory Society policy statement on disparities in respiratory health. Attainment of respiratory health equality requires the ending of respiratory health disparities, which can be achieved only through multidisciplinary efforts to eliminate detrimental environmental exposures while promoting a healthy lifestyle, implementing all components of high-quality health care (prevention, screening, diagnosis, and treatment), and conducting research that will lead to better prevention and management of respiratory diseases for everyone. The ATS recognizes that such efforts must include all stakeholders: members of society at large, governmental and nongovernmental organizations, and other professional societies. The ATS urges all of its members and those of sister societies to work to achieve this laudable goal.

Respiratory Health Equality in the United States. The American Thoracic Society Perspective

PubMed Central

Roman, Jesse; Schraufnagel, Dean E.; Thomas, Alvin; Samet, Jonathan

2014-01-01

Because the frequency of major risk factors for respiratory diseases (e.g., tobacco use) differs across demographic groups (defined by socioeconomic status, race/ethnicity, sexual orientation, health care access, occupation, or other characteristics), health disparities are commonly encountered in pediatric and adult pulmonary, critical care, and sleep medicine. As part of its policy on respiratory health disparities, the American Thoracic Society (ATS) Executive Committee created a Health Equality Subcommittee of the Health Policy Committee, with an initial mandate of defining respiratory health equality and, as a subsequent task, providing recommendations to the ATS leadership as to how our society may help attain such equality in the United States. After receiving input from the ATS assemblies and committees, the subcommittee developed this document on respiratory health equality. This document defines respiratory health disparities and respiratory health equality, and expands on a recent ATS and European Respiratory Society policy statement on disparities in respiratory health. Attainment of respiratory health equality requires the ending of respiratory health disparities, which can be achieved only through multidisciplinary efforts to eliminate detrimental environmental exposures while promoting a healthy lifestyle, implementing all components of high-quality health care (prevention, screening, diagnosis, and treatment), and conducting research that will lead to better prevention and management of respiratory diseases for everyone. The ATS recognizes that such efforts must include all stakeholders: members of society at large, governmental and nongovernmental organizations, and other professional societies. The ATS urges all of its members and those of sister societies to work to achieve this laudable goal. PMID:24625275

Analysing the health effects of simultaneous exposure to physical and chemical properties of airborne particles

PubMed Central

Pirani, Monica; Best, Nicky; Blangiardo, Marta; Liverani, Silvia; Atkinson, Richard W.; Fuller, Gary W.

2015-01-01

Background Airborne particles are a complex mix of organic and inorganic compounds, with a range of physical and chemical properties. Estimation of how simultaneous exposure to air particles affects the risk of adverse health response represents a challenge for scientific research and air quality management. In this paper, we present a Bayesian approach that can tackle this problem within the framework of time series analysis. Methods We used Dirichlet process mixture models to cluster time points with similar multipollutant and response profiles, while adjusting for seasonal cycles, trends and temporal components. Inference was carried out via Markov Chain Monte Carlo methods. We illustrated our approach using daily data of a range of particle metrics and respiratory mortality for London (UK) 2002–2005. To better quantify the average health impact of these particles, we measured the same set of metrics in 2012, and we computed and compared the posterior predictive distributions of mortality under the exposure scenario in 2012 vs 2005. Results The model resulted in a partition of the days into three clusters. We found a relative risk of 1.02 (95% credible intervals (CI): 1.00, 1.04) for respiratory mortality associated with days characterised by high posterior estimates of non-primary particles, especially nitrate and sulphate. We found a consistent reduction in the airborne particles in 2012 vs 2005 and the analysis of the posterior predictive distributions of respiratory mortality suggested an average annual decrease of − 3.5% (95% CI: − 0.12%, − 5.74%). Conclusions We proposed an effective approach that enabled the better understanding of hidden structures in multipollutant health effects within time series analysis. It allowed the identification of exposure metrics associated with respiratory mortality and provided a tool to assess the changes in health effects from various policies to control the ambient particle matter mixtures. PMID:25795926

Analysing the health effects of simultaneous exposure to physical and chemical properties of airborne particles.

PubMed

Pirani, Monica; Best, Nicky; Blangiardo, Marta; Liverani, Silvia; Atkinson, Richard W; Fuller, Gary W

2015-06-01

Airborne particles are a complex mix of organic and inorganic compounds, with a range of physical and chemical properties. Estimation of how simultaneous exposure to air particles affects the risk of adverse health response represents a challenge for scientific research and air quality management. In this paper, we present a Bayesian approach that can tackle this problem within the framework of time series analysis. We used Dirichlet process mixture models to cluster time points with similar multipollutant and response profiles, while adjusting for seasonal cycles, trends and temporal components. Inference was carried out via Markov Chain Monte Carlo methods. We illustrated our approach using daily data of a range of particle metrics and respiratory mortality for London (UK) 2002-2005. To better quantify the average health impact of these particles, we measured the same set of metrics in 2012, and we computed and compared the posterior predictive distributions of mortality under the exposure scenario in 2012 vs 2005. The model resulted in a partition of the days into three clusters. We found a relative risk of 1.02 (95% credible intervals (CI): 1.00, 1.04) for respiratory mortality associated with days characterised by high posterior estimates of non-primary particles, especially nitrate and sulphate. We found a consistent reduction in the airborne particles in 2012 vs 2005 and the analysis of the posterior predictive distributions of respiratory mortality suggested an average annual decrease of -3.5% (95% CI: -0.12%, -5.74%). We proposed an effective approach that enabled the better understanding of hidden structures in multipollutant health effects within time series analysis. It allowed the identification of exposure metrics associated with respiratory mortality and provided a tool to assess the changes in health effects from various policies to control the ambient particle matter mixtures. Copyright © 2015. Published by Elsevier Ltd.

Physiology of respiratory disturbances in muscular dystrophies

PubMed Central

Lo Mauro, Antonella

2016-01-01

Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. Key points A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination. In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia. Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness. Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase. The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. Educational aims To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy. To understand the impact of respiratory disturbances in patients with muscular dystrophy. To provide a brief description of the main forms of muscular dystrophy with their respiratory implications. PMID:28210319

Physiology of respiratory disturbances in muscular dystrophies.

PubMed

Lo Mauro, Antonella; Aliverti, Andrea

2016-12-01

Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e . when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination.In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia.Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness.Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase.The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. To understand the mechanisms leading to respiratory disturbances in patients with muscular dystrophy.To understand the impact of respiratory disturbances in patients with muscular dystrophy.To provide a brief description of the main forms of muscular dystrophy with their respiratory implications.

Copper supplementation restores cytochrome c oxidase assembly defect in a mitochondrial disease model of COA6 deficiency.

PubMed

Ghosh, Alok; Trivedi, Prachi P; Timbalia, Shrishiv A; Griffin, Aaron T; Rahn, Jennifer J; Chan, Sherine S L; Gohil, Vishal M

2014-07-01

Mitochondrial respiratory chain biogenesis is orchestrated by hundreds of assembly factors, many of which are yet to be discovered. Using an integrative approach based on clues from evolutionary history, protein localization and human genetics, we have identified a conserved mitochondrial protein, C1orf31/COA6, and shown its requirement for respiratory complex IV biogenesis in yeast, zebrafish and human cells. A recent next-generation sequencing study reported potential pathogenic mutations within the evolutionarily conserved Cx₉CxnCx₁₀C motif of COA6, implicating it in mitochondrial disease biology. Using yeast coa6Δ cells, we show that conserved residues in the motif, including the residue mutated in a patient with mitochondrial disease, are essential for COA6 function, thus confirming the pathogenicity of the patient mutation. Furthermore, we show that zebrafish embryos with zfcoa6 knockdown display reduced heart rate and cardiac developmental defects, recapitulating the observed pathology in the human mitochondrial disease patient who died of neonatal hypertrophic cardiomyopathy. The specific requirement of Coa6 for respiratory complex IV biogenesis, its intramitochondrial localization and the presence of the Cx₉CxnCx₁₀C motif suggested a role in mitochondrial copper metabolism. In support of this, we show that exogenous copper supplementation completely rescues respiratory and complex IV assembly defects in yeast coa6Δ cells. Taken together, our results establish an evolutionarily conserved role of Coa6 in complex IV assembly and support a causal role of the COA6 mutation in the human mitochondrial disease patient. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com

This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged andmore » dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.« less

Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts.

PubMed

Felici, Roberta; Lapucci, Andrea; Cavone, Leonardo; Pratesi, Sara; Berlinguer-Palmini, Rolando; Chiarugi, Alberto

2015-06-01

Mitochondrial disorders are devastating genetic diseases for which efficacious therapies are still an unmet need. Recent studies report that increased availability of intracellular NAD obtained by inhibition of the NAD-consuming enzyme poly(ADP-ribose) polymerase (PARP)-1 or supplementation with the NAD-precursor nicotinamide riboside (NR) ameliorates energetic derangement and symptoms in mouse models of mitochondrial disorders. Whether these pharmacological approaches also improve bioenergetics of human cells harboring mitochondrial defects is unknown. It is also unclear whether the same signaling cascade is prompted by PARP-1 inhibitors and NR supplementation to improve mitochondrial homeostasis. Here, we show that human fibroblasts mutant for the NADH dehydrogenase (ubiquinone) Fe-S protein 1 (NDUFS1) subunit of respiratory complex I have similar ATP, NAD, and mitochondrial content compared with control cells, but show reduced mitochondrial membrane potential. Interestingly, mutant cells also show increased transcript levels of mitochondrial DNA but not nuclear DNA respiratory complex subunits, suggesting activation of a compensatory response. At variance with prior work in mice, however, NR supplementation, but not PARP-1 inhibition, increased intracellular NAD content in NDUFS1 mutant human fibroblasts. Conversely, PARP-1 inhibitors, but not NR supplementation, increased transcription of mitochondrial transcription factor A and mitochondrial DNA-encoded respiratory complexes constitutively induced in mutant cells. Still, both NR and PARP-1 inhibitors restored mitochondrial membrane potential and increased organelle content as well as oxidative activity of NDUFS1-deficient fibroblasts. Overall, data provide the first evidence that in human cells harboring a mitochondrial respiratory defect exposure to NR or PARP-1, inhibitors activate different signaling pathways that are not invariantly prompted by NAD increases, but equally able to improve energetic derangement. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Inferring cardiac phase response curve in vivo

NASA Astrophysics Data System (ADS)

Pikovsky, Arkady; Kralemann, Bjoern; Fruehwirth, Matthias; Rosenblum, Michael; Kenner, Thomas; Schaefer, Jochen; Moser, Maximilian

2014-03-01

Characterizing properties of biological oscillators with phase response cirves (PRC) is one of main theoretical tools in neuroscience, cardio-respiratory physiology, and chronobiology. We present a technique that allows the extraction of the PRC from a non-invasive observation of a system consisting of two interacting oscillators, in this case heartbeat and respiration, in its natural environment and under free-running conditions. We use this method to obtain the phase coupling functions describing cardio-respiratory interactions and the phase response curve of 17 healthy humans. We show at which phase the cardiac beat is susceptible to respiratory drive and extract the respiratory-related component of heart rate variability. This non-invasive method of bivariate data analysis for the determination of phase response curves of coupled oscillators may find application in other biological and physical systems.

Evaluation of GeneXpert MTB/RIF for detection of Mycobacterium tuberculosis complex and rpo B gene in respiratory and non-respiratory clinical specimens at a tertiary care teaching hospital in Saudi Arabia.

PubMed

Somily, Ali M; Barry, Mazin A; Habib, Hanan A; Alotaibi, Fawzia E; Al-Zamil, Fahad A; Khan, Mohammed A; Sarwar, Mohammed S; Bakhash, Nawab D; Alrabiaah, Abdulkarim A; Shakoor, Zahid A; Senok, Abiola C

2016-12-01

To assess the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), against smear microscopy and culture method for diagnosis of MTB infection. Methods: This is a retrospective analysis of 103 respiratory and 137 non-respiratory patient specimens suspected of tuberculosis at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia performed between April 2014 and March 2015. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test. Results: Fifteen out of 103 respiratory samples were smear and culture positive, whereas 9 out of 137 non-respiratory samples were smear positive. Out of 9 smear positive specimens, 8 were also culture positive. All 15 culture positive respiratory samples were detected by Xpert MTB/RIF (sensitivity  and positive predictive value [PPV]=100%). Similarly, all 8 culture positive non-respiratory specimens were identified by Xpert MTB/RIF (sensitivity 100%; PPV 88.8%). The Xpert MTB/RIF detected only one false positive result in 88 smear negative respiratory specimens (specificity 98.9%; negative predictive value [NPV]= 100%). All 125 smear negative non-respiratory specimens tested negative by culture and Xpert MTB/RIF (sensitivity, specificity, PPV, NPV= 100%). Conclusion: The performance of Xpert MTB/RIF was comparable to the gold standard culture method for identification of MTB in both respiratory and non-respiratory clinical specimens.

Evaluation of GeneXpert MTB/RIF for detection of Mycobacterium tuberculosis complex and rpo B gene in respiratory and non-respiratory clinical specimens at a tertiary care teaching hospital in Saudi Arabia

PubMed Central

Somily, Ali M.; Barry, Mazin A.; Habib, Hanan A.; Alotaibi, Fawzia E.; Al-Zamil, Fahad A.; Khan, Mohammed A.; Sarwar, Mohammed S.; Bakhash, Nawab D.; Alrabiaah, Abdulkarim A.; Shakoor, Zahid A.; Senok, Abiola C.

2016-01-01

Objectives To assess the performance of Xpert MTB/RIF, an automated molecular test for Mycobacterium tuberculosis (MTB) and resistance to rifampin (RIF), against smear microscopy and culture method for diagnosis of MTB infection. Methods This is a retrospective analysis of 103 respiratory and 137 non-respiratory patient specimens suspected of tuberculosis at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia performed between April 2014 and March 2015. Each sample underwent smear microscopy, mycobacterial culture, and GeneXpert MTB/RIF test. Results Fifteen out of 103 respiratory samples were smear and culture positive, whereas 9 out of 137 non-respiratory samples were smear positive. Out of 9 smear positive specimens, 8 were also culture positive. All 15 culture positive respiratory samples were detected by Xpert MTB/RIF (sensitivity and positive predictive value [PPV]=100%). Similarly, all 8 culture positive non-respiratory specimens were identified by Xpert MTB/RIF (sensitivity 100%; PPV 88.8%). The Xpert MTB/RIF detected only one false positive result in 88 smear negative respiratory specimens (specificity 98.9%; negative predictive value [NPV]= 100%). All 125 smear negative non-respiratory specimens tested negative by culture and Xpert MTB/RIF (sensitivity, specificity, PPV, NPV= 100%). Conclusion The performance of Xpert MTB/RIF was comparable to the gold standard culture method for identification of MTB in both respiratory and non-respiratory clinical specimens. PMID:27874159

Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis

PubMed Central

Wittmeier, Steffen; Song, Gang; Duffin, James; Poon, Chi-Sang

2008-01-01

Inspiratory and expiratory rhythms in mammals are thought to be generated by pacemaker-like neurons in 2 discrete brainstem regions: pre-Bötzinger complex (preBötC) and parafacial respiratory group (pFRG). How these putative pacemakers or pacemaker networks may interact to set the overall respiratory rhythm in synchrony remains unclear. Here, we show that a pacemakers 2-way “handshake” process comprising pFRG excitation of the preBötC, followed by reverse inhibition and postinhibitory rebound (PIR) excitation of the pFRG and postinspiratory feedback inhibition of the preBötC, can provide a phase-locked mechanism that sequentially resets and, hence, synchronizes the inspiratory and expiratory rhythms in neonates. The order of this handshake sequence and its progression vary depending on the relative excitabilities of the preBötC vs. the pFRG and resultant modulations of the PIR in various excited and depressed states, leading to complex inspiratory and expiratory phase-resetting behaviors in neonates and adults. This parsimonious model of pacemakers synchronization and mutual entrainment replicates key experimental data in vitro and in vivo that delineate the developmental changes in respiratory rhythm from neonates to maturity, elucidating their underlying mechanisms and suggesting hypotheses for further experimental testing. Such a pacemakers handshake process with conjugate excitation–inhibition and PIR provides a reinforcing and evolutionarily advantageous fail-safe mechanism for respiratory rhythmogenesis in mammals. PMID:19008356

[Evaluation of Xpert® MTB/RIF technique for Mycobacterium tuberculosis complex detection in extra-respiratory specimens].

PubMed

García, Patricia; Balcells, M Elvira; Castillo, Claudia; Miranda, Carolina; Geoffroy, Enrique; Román, Juan C; Wozniak, Aniela

2017-08-01

Extra-pulmonary tuberculosis (TB) represents the 26.2% of total TB cases in Chile. Culture is the gold standard method, but the process is extremely slow. Xpert®MTB/RIF technique detects Mycobacterium tuberculosis complex (MTBc) through real time PCR in less than 3 h. However, it has been validated only for respiratory specimens. We aimed to determine the performance of Xpert®MTB/RIF test in detecting MTBc in extra-respiratory specimens compared with a combined gold standard consisting in a positive (liquid and solid) mycobacterial culture and/or a positive validated molecular method (q-RPC, Cobas®TaqMan®-MTB). Fifty extra-respiratory specimens were analyzed, from which 25 were positive and 25 negative for MTBc based on the combined gold standard. The 25 positive specimens had a positive result by Xpert®MTB/RIF; from the 25 negative specimens, 24 had a negative result and one had a positive result. We obtained an overall concordance of 98% between Xpert®MTB/RIF and the combined gold standard. Xpert®MTB/RIF test was able to detect 12 smear-negative specimens and 3 culture-negative specimens, all of them corresponding to extra-pulmonary TB cases. Xpert®MTB/RIF showed similar sensitivity to q-RPC in detecting MTBc in extra-respiratory specimens. This procedure allowed a substantial reduction in the time of diagnosis.

Interaction between telencephalic signals and respiratory dynamics in songbirds

PubMed Central

Méndez, Jorge M.; Mindlin, Gabriel B.

2012-01-01

The mechanisms by which telencephalic areas affect motor activities are largely unknown. They could either take over motor control from downstream motor circuits or interact with the intrinsic dynamics of these circuits. Both models have been proposed for telencephalic control of respiration during learned vocal behavior in birds. The interactive model postulates that simple signals from the telencephalic song control areas are sufficient to drive the nonlinear respiratory network into producing complex temporal sequences. We tested this basic assumption by electrically stimulating telencephalic song control areas and analyzing the resulting respiratory patterns in zebra finches and in canaries. We found strong evidence for interaction between the rhythm of stimulation and the intrinsic respiratory rhythm, including naturally emerging subharmonic behavior and integration of lateralized telencephalic input. The evidence for clear interaction in our experimental paradigm suggests that telencephalic vocal control also uses a similar mechanism. Furthermore, species differences in the response of the respiratory system to stimulation show parallels to differences in the respiratory patterns of song, suggesting that the interactive production of respiratory rhythms is manifested in species-specific specialization of the involved circuitry. PMID:22402649

Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

PubMed Central

Hulse, Elspeth J.; Davies, James O. J.; Simpson, A. John; Sciuto, Alfred M.

2014-01-01

Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities. PMID:25419614

Physiology and pathophysiology of respiratory arrest by cyanide poisoning

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

Klimmek, R.

1993-05-13

Respiratory arrest, preceded by hyperventilation, is the primary cause of death in acute cyanide poisoning. Hyperventilation followed by apnea is also observed without intoxication. Hyperventilation and apnea in untoxicated subjects and animals are analyzed for the underlying physiological and biochemical changes and compared with those found during cyanide poisoning. The study reveals that the respiratory autoregulation appears to be the same under both conditions. Respiratory arrest is controlled by cerebral PCO2 and can occur without hypoxia or inhibition of cytochrome oxidase. It is postulated that respiratory arrest is a 'desperate act' thrust on the respiratory neurons by a critical exhaustionmore » of their energy store (ATP) due to the rapid firing in the period of hyperventilation. The point of no return may be reached when anoxia and/or partial inhibition of cytochrome oxidase prevent the neurons from replenishing the ATP store. The formation of Fe3+ cyanide complexes. exemplified by the metHb producer DMAP, appears to give the best results with regard to the restoration of spontaneous respiration. The study of respiratory autoregulation may also be helpful in developing and understanding other therapeutic approaches.« less

Expression of the transcription factor FOXP2 in brainstem respiratory circuits of adult rat is restricted to upper-airway pre-motor areas.

PubMed

Stanić, Davor; Dhingra, Rishi R; Dutschmann, Mathias

2018-04-01

Expression of the transcription factor FOXP2 is linked to brain circuits that control motor function and speech. Investigation of FOXP2 protein expression in respiratory areas of the ponto-medullary brainstem of adult rat revealed distinct rostro-caudal expression gradients. A high density of FOXP2 immunoreactive nuclei was observed within the rostral pontine Kölliker-Fuse nucleus, compared to low densities in caudal pontine and rostral medullary respiratory nuclei, including the: (i) noradrenergic A5 and parafacial respiratory groups; (ii) Bötzinger and pre-Bötzinger complex and; (iii) rostral ventral respiratory group. Moderate densities of FOXP2 immunoreactive nuclei were observed in the caudal ventral respiratory group and the nucleus retroambiguus, with significant density levels found in the caudal half of the dorsal respiratory group and the hypoglossal pre-motor area lateral around calamus scriptorius. FOXP2 immunoreactivity was absent in all cranial nerve motor nuclei. We conclude that FOXP2 expression in respiratory brainstem areas selectively delineates laryngeal and hypoglossal pre-motor neuron populations essential for the generation of sound and voice. Copyright © 2018 Elsevier B.V. All rights reserved.

Towards understanding the complexity of cardiovascular oscillations: Insights from information theory.

PubMed

Javorka, Michal; Krohova, Jana; Czippelova, Barbora; Turianikova, Zuzana; Lazarova, Zuzana; Wiszt, Radovan; Faes, Luca

2018-07-01

Cardiovascular complexity is a feature of healthy physiological regulation, which stems from the simultaneous activity of several cardiovascular reflexes and other non-reflex physiological mechanisms. It is manifested in the rich dynamics characterizing the spontaneous heart rate and blood pressure variability (HRV and BPV). The present study faces the challenge of disclosing the origin of short-term HRV and BPV from the statistical perspective offered by information theory. To dissect the physiological mechanisms giving rise to cardiovascular complexity in different conditions, measures of predictive information, information storage, information transfer and information modification were applied to the beat-to-beat variability of heart period (HP), systolic arterial pressure (SAP) and respiratory volume signal recorded non-invasively in 61 healthy young subjects at supine rest and during head-up tilt (HUT) and mental arithmetics (MA). Information decomposition enabled to assess simultaneously several expected and newly inferred physiological phenomena, including: (i) the decreased complexity of HP during HUT and the increased complexity of SAP during MA; (ii) the suppressed cardiorespiratory information transfer, related to weakened respiratory sinus arrhythmia, under both challenges; (iii) the altered balance of the information transferred along the two arms of the cardiovascular loop during HUT, with larger baroreflex involvement and smaller feedforward mechanical effects; and (iv) an increased importance of direct respiratory effects on SAP during HUT, and on both HP and SAP during MA. We demonstrate that a decomposition of the information contained in cardiovascular oscillations can reveal subtle changes in system dynamics and improve our understanding of the complexity changes during physiological challenges. Copyright © 2018. Published by Elsevier Ltd.

ECG-derived respiration based on iterated Hilbert transform and Hilbert vibration decomposition.

PubMed

Sharma, Hemant; Sharma, K K

2018-06-01

Monitoring of the respiration using the electrocardiogram (ECG) is desirable for the simultaneous study of cardiac activities and the respiration in the aspects of comfort, mobility, and cost of the healthcare system. This paper proposes a new approach for deriving the respiration from single-lead ECG based on the iterated Hilbert transform (IHT) and the Hilbert vibration decomposition (HVD). The ECG signal is first decomposed into the multicomponent sinusoidal signals using the IHT technique. Afterward, the lower order amplitude components obtained from the IHT are filtered using the HVD to extract the respiration information. Experiments are performed on the Fantasia and Apnea-ECG datasets. The performance of the proposed ECG-derived respiration (EDR) approach is compared with the existing techniques including the principal component analysis (PCA), R-peak amplitudes (RPA), respiratory sinus arrhythmia (RSA), slopes of the QRS complex, and R-wave angle. The proposed technique showed the higher median values of correlation (first and third quartile) for both the Fantasia and Apnea-ECG datasets as 0.699 (0.55, 0.82) and 0.57 (0.40, 0.73), respectively. Also, the proposed algorithm provided the lowest values of the mean absolute error and the average percentage error computed from the EDR and reference (recorded) respiration signals for both the Fantasia and Apnea-ECG datasets as 1.27 and 9.3%, and 1.35 and 10.2%, respectively. In the experiments performed over different age group subjects of the Fantasia dataset, the proposed algorithm provided effective results in the younger population but outperformed the existing techniques in the case of elderly subjects. The proposed EDR technique has the advantages over existing techniques in terms of the better agreement in the respiratory rates and specifically, it reduces the need for an extra step required for the detection of fiducial points in the ECG for the estimation of respiration which makes the process effective and less-complex. The above performance results obtained from two different datasets validate that the proposed approach can be used for monitoring of the respiration using single-lead ECG.

Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature.

PubMed

Zhou, Qiangjun; Zhai, Yujia; Lou, Jizhong; Liu, Man; Pang, Xiaoyun; Sun, Fei

2011-07-01

The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC(50) ~100 μmol/L) and the significant structure-based binding affinity calculation (~94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.

Biventricular non-compaction hypertrophic cardiomyopathy in association with congenital complete heart block and type I mitochondrial complex deficiency.

PubMed

Dhar, Ranjana; Reardon, William; McMahon, Colin J

2015-06-01

We report a baby girl with an antenatal diagnosis of biventricular non-compaction and complete heart block detected at 22 weeks' gestation. Postnatal echocardiography confirmed severe biventricular non-compaction hypertrophic cardiomyopathy, multiple muscular ventricular septal defects, and mild-moderate pulmonary valve stenosis. Skeletal muscle biopsy confirmed complex 1 mitochondrial respiratory chain deficiency. An epicardial VVI pacemaker was implanted on day 3 of life and revised at 7 years of age. She remains stable at 8 years of age following pacing and medical treatment with carvedilol, aspirin, co-enzyme Q10, and carnitine. This represents the first report of biventricular non-compaction hypertrophic phenotype in association with congenital complete heart block and complex 1 mitochondrial respiratory chain deficiency in a child.

1,3-Butadiene-Induced Mitochondrial Dysfunction is Correlated with Mitochondrial CYP2E1 Activity in Collaborative Cross Mice

PubMed Central

Hartman, Jessica H.; Miller, Grover P.; Caro, Andres A.; Byrum, Stephanie D.; Orr, Lisa M.; Mackintosh, Samuel G.; Tackett, Alan J.; MacMillan-Crow, Lee Ann; Hallberg, Lance M.; Ameredes, Bill T.; Boysen, Gunnar

2017-01-01

Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight hydrophobic compounds, including 1,3-butadiene, which is converted by CYP2E1 to electrophilic epoxide metabolites that covalently modify cellular proteins and DNA. Previous CYP2E1 studies have mainly focused on the enzyme localized in the endoplasmic reticulum (erCYP2E1); however, active CYP2E1 also localizes in mitochondria (mtCYP2E1) and the distribution of CYP2E1 between organelles can influence an individual's response to exposure. Relatively few studies have focused on the contribution of mtCYP2E1 to activation of chemical toxicants. We hypothesized that CYP2E1 bioactivation of butadiene within mitochondria adversely affects mitochondrial respiratory complexes I-IV. A population of Collaborative Cross mice were exposed to air (control) or 200 ppm butadiene. Subcellular fractions (mitochondria, DNA, and microsomes) were collected from frozen livers and CYP2E1 activity was measured in microsomes and mitochondria. Individual activities of mitochondrial respiratory complexes I-IV were measured using in vitro assays with purified mitochondrial fractions. In air- and butadiene-exposed mouse samples, mtDNA copy numbers were assessed by RT-PCR, and mtDNA integrity was assessed through a PCR-based assay. No significant change in mtDNA copy number or integrity were observed; however, there was a decrease in overall activity of mitochondrial respiratory complexes I, II, and IV after butadiene exposure. Additionally, higher mtCYP2E1 (but not erCYP2E1) activity was correlated with decreased mitochondrial respiratory complex activity (in complexes I-IV) in the butadiene-exposed (not control) animals. Together, these results represent the first in vivo link between mitochondrial CYP2E1 activity and mitochondrial toxicity. PMID:28082109

Diagnosis and treatment of simple acid-base disorders.

PubMed

Ayers, Phil; Warrington, Laurie

2008-01-01

The ability to diagnose and treat acid-base disorders is an important component in the practice of the nutrition support clinician. A complete understanding of the basic principles of metabolic and respiratory disorders allows the practitioner to formulate educated decisions regarding fluids, parenteral nutrition salts, and the management of electrolytes. This review will discuss the diagnosis and treatment of common metabolic and respiratory disorders encountered in nutrition support practice.

Achondroplasia-hypochondroplasia complex and abnormal pulmonary anatomy.

PubMed

Bober, Michael B; Taylor, Megan; Heinle, Robert; Mackenzie, William

2012-09-01

Achondroplasia and hypochondroplasia are two of the most common forms of skeletal dysplasia. They are both caused by activating mutations in FGFR3 and are inherited in an autosomal dominant manner. Our patient was born to parents with presumed achondroplasia, and found on prenatal testing to have p.G380R and p.N540K FGFR3 mutations. In addition to having typical problems associated with both achondroplasia and hypochondroplasia, our patient had several atypical findings including: abnormal lobulation of the lungs with respiratory insufficiency, C1 stenosis, and hypoglycemia following a Nissen fundoplication. After his reflux and aspiration were treated, the persistence of the tachypnea and increased respiratory effort indicated this was not the primary source of the respiratory distress. Our subsequent hypothesis was that primary restrictive lung disease was the cause of his respiratory distress. A closer examination of his chest circumference did not support this conclusion either. Following his death, an autopsy found the right lung had 2 lobes while the left lung had 3 lobes. A literature review demonstrates that other children with achondroplasia-hypochondroplasia complex have been described with abnormal pulmonary function and infants with thanatophoric dysplasia have similar abnormal pulmonary anatomy. We hypothesize that there may be a primary pulmonary phenotype associated with FGFR3-opathies, unrelated to chest size which leads to the consistent finding of increased respiratory signs and symptoms in these children. Further observation of respiratory status, combined with the macroscopic and microscopic analysis of pulmonary branching anatomy and alveolar structure in this patient population will be important to explore this hypothesis. Copyright © 2012 Wiley Periodicals, Inc.

Structure, function and evolution of the gas exchangers: comparative perspectives

PubMed Central

Maina, JN

2002-01-01

Over the evolutionary continuum, animals have faced similar fundamental challenges of acquiring molecular oxygen for aerobic metabolism. Under limitations and constraints imposed by factors such as phylogeny, behaviour, body size and environment, they have responded differently in founding optimal respiratory structures. A quintessence of the aphorism that ‘necessity is the mother of invention’, gas exchangers have been inaugurated through stiff cost–benefit analyses that have evoked transaction of trade-offs and compromises. Cogent structural–functional correlations occur in constructions of gas exchangers: within and between taxa, morphological complexity and respiratory efficiency increase with metabolic capacities and oxygen needs. Highly active, small endotherms have relatively better-refined gas exchangers compared with large, inactive ectotherms. Respiratory structures have developed from the plain cell membrane of the primeval prokaryotic unicells to complex multifunctional ones ofthe modern Metazoa. Regarding the respiratory medium used to extract oxygen from, animal life has had only two choices – water or air – within the biological range of temperature and pressure the only naturally occurring respirable fluids. In rarer cases, certain animalshave adapted to using both media. Gills (evaginated gas exchangers) are the primordial respiratory organs: they are the archetypal water breathing organs. Lungs (invaginated gas exchangers) are the model air breathing organs. Bimodal (transitional) breathers occupy the water–air interface. Presentation and exposure of external (water/air) and internal (haemolymph/blood) respiratory media, features determined by geometric arrangement of the conduits, are important features for gas exchange efficiency: counter-current, cross-current, uniform pool and infinite pool designs have variably developed. PMID:12430953

The bioreactivity of the sub-10 μm component of volcanic ash: Soufrière Hills volcano, Montserrat.

PubMed

Jones, Timothy; Bérubé, Kelly

2011-10-30

With the recent eruption of the Icelandic volcano Eyafallajökull and resulting ash cloud over much of Europe there was considerable concern about possible respiratory hazards. Volcanic ash can contain minerals that are known human respiratory health hazards such as cristobalite. Short-term ash exposures can cause skin sores, respiratory and ocular irritations and exacerbation of pre-existing lung conditions such as asthma. Long-term occupational level exposures to crystalline silicon dioxide can cause lung inflammation, oedema, fibrosis and cancer. The potential health effects would be dependent on factors including mineralogy, surface chemistry, size, and levels and duration of exposure. Bulk ash from the Soufrière Hills volcano was sourced and inhalable (<2.5 μm) ash samples prepared and physicochemically characterised. The fine ash samples were tested for bioreactivity by SDS-PAGE which determined the strength of binding between mineral grains and lung proteins. Selected proteins bound tightly to cristobalite, and bound loosely to other ash components. A positive correlation was seen between the amount of SiO(2) in the sample and the strength of the binding. The strength of binding is a function of the mineral's bioreactivity, and therefore, a potential geo-biomarker of respiratory risk. Copyright © 2011 Elsevier B.V. All rights reserved.

Impacts of air pollution exposure on the allergenic properties of Arizona cypress pollens

NASA Astrophysics Data System (ADS)

Shahali, Y.; Pourpak, Z.; Moin, M.; Zare, A.; Majd, A.

2009-02-01

Epidemiological studies have demonstrated that urbanization and high levels of vehicle emissions correlated with the increasing trend of pollen-induced respiratory allergies. Numerous works have investigated the role of pollutants in the pathogenesis of respiratory diseases but impacts of anthropogenic pollution on pollen allergenic properties are still poorly understood. The objective of this survey was to evaluate impacts of the traffic-related pollution on the structure and allergenic protein content of Arizona cypress (Cupressus arizonica, CA) pollens, recognized as a rising cause of seasonal allergy in various regions worldwide. According to our results, traffic-related air pollution by its direct effects on the elemental composition of pollens considerably increased the fragility of the pollen exine, causing numerous cracks in its surface and facilitating pollen content liberation. Pollen grains were also covered by numerous submicronic orbicules which may act as effective vectors for pollen-released components into the lower regions of respiratory organs. On the other hand, this study provides us reliable explications about the low efficiency of standard commercial allergens in the diagnosis of the Arizona cypress pollen allergy in Tehran. Although traffic related pollution affects the allergenic components of CA pollens, the repercussions on the respiratory health of urban populations have yet to be clarified and need further investigations.

Effects of viral respiratory disease education and surveillance on antibiotic prescribing.

PubMed

Temte, J L; Shult, P A; Kirk, C J; Amspaugh, J

1999-02-01

We describe a partnership between family practice residency clinics and a state public health virology laboratory that has produced comprehensive viral respiratory disease education and surveillance. Family practice residents have been provided with education on respiratory viruses and the results of ongoing viral surveillance. The preliminary effects of this program on antibiotic prescribing by senior residents are evaluated in this paper. We used a questionnaire to assess the acceptance by family practice residents of the educational component and the utility of ongoing viral surveillance. We used chart review to evaluate rates of antibiotic prescribing and the number of patients diagnosed per year with acute upper respiratory infection and acute bronchitis by senior residents in 1992 (preexposure) and 1996 (postexposure). By the third year of training, most residents (79%) reported receiving adequate training regarding common viral respiratory diseases. Moreover, residents reported that they were less likely to prescribe antibiotics to patients presenting with respiratory infections when provided with specific information on circulating viral pathogens. Antibiotic prescribing in the postexposure group was 68% lower for upper respiratory infection (URI) and 45% lower for a composite of URI and bronchitis. Education and monitoring of circulating respiratory viruses can result in familiarity with common disorders in primary care and reduce unnecessary antibiotic use.

Fluorescence decay kinetics and imaging of NAD(P)H and flavins as metabolic indicators

NASA Astrophysics Data System (ADS)

Schneckenburger, Herbert; Koenig, Karsten

1992-07-01

The intrinsic fluorescence of various cell cultures in the blue and green spectral range has been attributed mainly to hydrated nicotinamide adenine dinucleotide (NADH) and flavin molecules. Their fluorescence decay curves were measured with subnanosecond resolution. The reduced coenzymes NADH and hydrated nicotinamide adenine dinucleotide phosphate NADPH, both showed a biexponential decay pattern in solution with similar time constants, but different relative intensities of the two components. They could thus be distinguished from one another as well as from their oxidized forms. The NADPH fluorescence of Saccharomyces cerevisiae was located within the cytoplasm and its organelles and was by about a factor of 4 higher for respiratory-deficient than for intact yeast strains. Intracellular flavin fluorescence showed a triexponential behavior--probably due to a superposition of protein-bound and free flavin molecules. The lifetime of the shortest component varied within the range of 0.20 to 0.50 ns between respiratory-deficient and intact yeast strains, and the relative intensity of this component was most pronounced for the intact strain DL1. Time- resolved fluorescence seems therefore to be an appropriate method of probe the function of the respiratory chain and--in the further step--to differentiate between various types of cells and tissues in medical diagnosis or environmental research.

Assessment of continuous acoustic respiratory rate monitoring as an addition to a pulse oximetry-based patient surveillance system.

PubMed

McGrath, Susan P; Pyke, Joshua; Taenzer, Andreas H

2017-06-01

Technology advances make it possible to consider continuous acoustic respiratory rate monitoring as an integral component of physiologic surveillance systems. This study explores technical and logistical aspects of augmenting pulse oximetry-based patient surveillance systems with continuous respiratory rate monitoring and offers some insight into the impact on patient deterioration detection that may result. Acoustic respiratory rate sensors were introduced to a general care pulse oximetry-based surveillance system with respiratory rate alarms deactivated. Simulation was used after 4324 patient days to determine appropriate alarm thresholds for respiratory rate, which were then activated. Data were collected for an additional 4382 patient days. Physiologic parameters, alarm data, sensor utilization and patient/staff feedback were collected throughout the study and analyzed. No notable technical or workflow issues were observed. Sensor utilization was 57 %, with patient refusal leading reasons for nonuse (22.7 %). With respiratory rate alarm thresholds set to 6 and 40 breaths/min., the majority of nurse pager clinical notifications were triggered by low oxygen saturation values (43 %), followed by low respiratory rate values (21 %) and low pulse rate values (13 %). Mean respiratory rate collected was 16.6 ± 3.8 breaths/min. The vast majority (82 %) of low oxygen saturation states coincided with normal respiration rates of 12-20 breaths/min. Continuous respiratory rate monitoring can be successfully added to a pulse oximetry-based surveillance system without significant technical, logistical or workflow issues and is moderately well-tolerated by patients. Respiratory rate sensor alarms did not significantly impact overall system alarm burden. Respiratory rate and oxygen saturation distributions suggest adding continuous respiratory rate monitoring to a pulse oximetry-based surveillance system may not significantly improve patient deterioration detection.

Management of complex glottic stenosis in children with recurrent respiratory papillomatosis.

PubMed

Siegel, Bianca; Smith, Lee P

2013-10-01

To describe our management of complex glottic stenosis in tracheotomy dependent children with severe recurrent respiratory papillomatosis. Retrospective chart review at a tertiary care children's hospital. Three children with complex glottic stenosis secondary to severe recurrent respiratory papillomatosis were treated at our institution since 2011. Two patients had complete stenosis, and the third had near-complete stenosis. Two patients were managed using balloon dilation alone, and the third also underwent laryngotracheal reconstruction with posterior costal cartilage grafting. Two patients have been successfully decannulated and the third has been tolerating continuous tracheotomy capping for greater than twelve months. All three patients underwent aggressive debridement of papillomatosis and balloon dilation every 4-6 weeks until their burden of disease was controlled. In two patients, the glottic airway was patent, and the third continued to have complete restenosis between procedures and required laryngotracheoplasty with multiple post-operative dilation procedures to establish an adequate glottic airway. Severe laryngeal stenosis is a well-described complication of recurrent respiratory papillomatosis, but its management is not well-defined. Aggressive management of papillomatosis with frequent debridement is critical in successfully managing laryngeal stenosis. Balloon dilation alone may be surprisingly effective in these patients, and laryngotracheoplasty can be used as an adjunct procedure in those patients who fail balloon dilation. Given the quality of life issues and concerns regarding distal spread of disease with tracheotomies in these patients, we feel that aggressive management and early decannulation is in the patient's best interest. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Direct and indirect measurements relevant to the assessment of fatigue of the respiratory muscles - review

NASA Astrophysics Data System (ADS)

Kuraszkiewicz, Bożena

2011-01-01

The purpose of this review is to present selected tests available with the potential to detect the development of respiratory muscle fatigue in normal subjects and patients. All reviewed techniques represent a part of a variety of measures and indices, which have been employed to assess this complex process at the present time.

Effects of soil pH and aluminum on plant respiration

Treesearch

Rakesh Minocha; Subhash C. Minocha

2005-01-01

Interactions among external (soil) pH, cellular pH, and their effects on respiratory metabolism are complex. While the effects of changes in the apoplastic pH on the cytosolic pH are not clearly understood, pH directly affects enzymatic reactions in the cell, and pH-regulated ion uptake has profound indirect effects on cellular respiratory metabolism. A major...

Genome sequencing, metabolic and antibiotic resistance phenotyping of diverse nasopharyngeal bacteria isolated from cattle in an epidemiological study of bovine respiratory disease

USDA-ARS?s Scientific Manuscript database

Problem: Despite over 100 years of research to reduce the incidence and impact of bovine respiratory disease complex (BRDC) in North American feed yard cattle, outbreaks still occur accounting for up to 75% of feed yard cattle morbidity. BRDC is the primary driver of health-related antibiotic trea...

Redox homeostasis and respiratory metabolism in camels (Camelus dromedaries): comparisons with domestic goats and laboratory rats and mice.

PubMed

Al-Otaiba, Amna; John, Annie; Al-Belooshi, Thekra; Raza, Haider

2010-11-01

We have previously reported the occurrence of multiple forms of drug-metabolizing enzymes in camel tissues. Here, we investigate glutathione (GSH)-dependent redox homeostasis, reactive oxygen species (ROS) production and mitochondrial respiratory functions in camel tissues and compare them with imported domestic goats and laboratory rats and mice. Cytochrome P450 2E1 (CYP 2E1) and GSH-metabolizing enzymes were differentially expressed in the liver and kidney of these animals. Camel liver has significantly lower GSH pool than that in goats, rats and mice. Mitochondria isolated from the tissues of these animals showed a comparable ability to metabolize specific substrates for respiratory enzyme complexes I, II/III and IV. These complexes were metabolically more active in the kidney than in the liver of all the species. Furthermore, the activity of complex IV in camel tissues was significantly lower than in other species. On the other hand, complex II/III activity in camel kidney was higher compared to the other species. In addition, as expected, we observed that inhibitors of these enzyme complexes augment the production of mitochondrial ROS in camel and goat tissues. These results help to better understand the metabolic ability and adaptation in desert camels in comparison with domestic goats and laboratory rats and mice since they are exposed to different environmental and dietary conditions. Our study may also have implications in the pharmacology and toxicology of drugs and pollutants in these species.

Mycoplasma hyorhinis is a potential pathogen of porcine respiratory disease complex that aggravates pneumonia caused by porcine reproductive and respiratory syndrome virus.

PubMed

Lee, Jung-Ah; Oh, Yu-Ri; Hwang, Min-A; Lee, Joong-Bok; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo; Lee, Sang-Won

2016-09-01

The porcine respiratory disease complex (PRDC) caused by numerous bacterial and viral agents has a great impact on pig industry worldwide. Although Mycoplasma hyorhinis (Mhr) has been frequently isolated from lung lesions from pigs with PRDC, the pathological importance of Mhr may have been underestimated. In this study, 383 serum samples obtained from seven herds with a history of PRDC were tested for specific antibodies to Mhr, Mycoplasma hyopneumoniae (Mhp), and porcine reproductive and respiratory syndrome virus (PRRSV). Seropositive rates of PRRSV were significantly correlated with those of Mhr (correlation coefficient, 0.862; P-value, 0.013), but not with those of Mhp (correlation coefficient, -0.555; P-value, 0.196). In vivo experiments demonstrated that pigs co-infected with Mhr and PRRSV induced more severe lung lesions than pigs infected with Mhr or PRRSV alone. These findings suggest that Mhr is closely associated with pneumonia caused by PRRSV and provide important information on Mhr pathogenesis within PRDC. Therefore, effective PRDC control strategies should also consider the potential impact of Mhr in the pathogenesis of PRDC. Copyright © 2016 Elsevier B.V. All rights reserved.

Morphology of Dbx1 respiratory neurons in the preBötzinger complex and reticular formation of neonatal mice.

PubMed

Akins, Victoria T; Weragalaarachchi, Krishanthi; Picardo, Maria Cristina D; Revill, Ann L; Del Negro, Christopher A

2017-08-01

The relationship between neuron morphology and function is a perennial issue in neuroscience. Information about synaptic integration, network connectivity, and the specific roles of neuronal subpopulations can be obtained through morphological analysis of key neurons within a microcircuit. Here we present morphologies of two classes of brainstem respiratory neurons. First, interneurons derived from Dbx1-expressing precursors (Dbx1 neurons) in the preBötzinger complex (preBötC) of the ventral medulla that generate the rhythm for inspiratory breathing movements. Second, Dbx1 neurons of the intermediate reticular formation that influence the motor pattern of pharyngeal and lingual movements during the inspiratory phase of the breathing cycle. We describe the image acquisition and subsequent digitization of morphologies of respiratory Dbx1 neurons from the preBötC and the intermediate reticular formation that were first recorded in vitro. These data can be analyzed comparatively to examine how morphology influences the roles of Dbx1 preBötC and Dbx1 reticular interneurons in respiration and can also be utilized to create morphologically accurate compartmental models for simulation and modeling of respiratory circuits.

Paramyxovirus glycoprotein incorporation, assembly and budding: a three way dance for infectious particle production.

PubMed

El Najjar, Farah; Schmitt, Anthony P; Dutch, Rebecca Ellis

2014-08-07

Paramyxoviruses are a family of negative sense RNA viruses whose members cause serious diseases in humans, such as measles virus, mumps virus and respiratory syncytial virus; and in animals, such as Newcastle disease virus and rinderpest virus. Paramyxovirus particles form by assembly of the viral matrix protein, the ribonucleoprotein complex and the surface glycoproteins at the plasma membrane of infected cells and subsequent viral budding. Two major glycoproteins expressed on the viral envelope, the attachment protein and the fusion protein, promote attachment of the virus to host cells and subsequent virus-cell membrane fusion. Incorporation of the surface glycoproteins into infectious progeny particles requires coordinated interplay between the three viral structural components, driven primarily by the matrix protein. In this review, we discuss recent progress in understanding the contributions of the matrix protein and glycoproteins in driving paramyxovirus assembly and budding while focusing on the viral protein interactions underlying this process and the intracellular trafficking pathways for targeting viral components to assembly sites. Differences in the mechanisms of particle production among the different family members will be highlighted throughout.

Paramyxovirus Glycoprotein Incorporation, Assembly and Budding: A Three Way Dance for Infectious Particle Production

PubMed Central

El Najjar, Farah; Schmitt, Anthony P.; Dutch, Rebecca Ellis

2014-01-01

Paramyxoviruses are a family of negative sense RNA viruses whose members cause serious diseases in humans, such as measles virus, mumps virus and respiratory syncytial virus; and in animals, such as Newcastle disease virus and rinderpest virus. Paramyxovirus particles form by assembly of the viral matrix protein, the ribonucleoprotein complex and the surface glycoproteins at the plasma membrane of infected cells and subsequent viral budding. Two major glycoproteins expressed on the viral envelope, the attachment protein and the fusion protein, promote attachment of the virus to host cells and subsequent virus-cell membrane fusion. Incorporation of the surface glycoproteins into infectious progeny particles requires coordinated interplay between the three viral structural components, driven primarily by the matrix protein. In this review, we discuss recent progress in understanding the contributions of the matrix protein and glycoproteins in driving paramyxovirus assembly and budding while focusing on the viral protein interactions underlying this process and the intracellular trafficking pathways for targeting viral components to assembly sites. Differences in the mechanisms of particle production among the different family members will be highlighted throughout. PMID:25105277

Changes in mitochondrial function and mitochondria associated protein expression in response to 2-weeks of high intensity interval training

PubMed Central

Vincent, Grace; Lamon, Séverine; Gant, Nicholas; Vincent, Peter J.; MacDonald, Julia R.; Markworth, James F.; Edge, Johann A.; Hickey, Anthony J. R.

2015-01-01

Purpose: High-intensity short-duration interval training (HIT) stimulates functional and metabolic adaptation in skeletal muscle, but the influence of HIT on mitochondrial function remains poorly studied in humans. Mitochondrial metabolism as well as mitochondrial-associated protein expression were tested in untrained participants performing HIT over a 2-week period. Methods: Eight males performed a single-leg cycling protocol (12 × 1 min intervals at 120% peak power output, 90 s recovery, 4 days/week). Muscle biopsies (vastus lateralis) were taken pre- and post-HIT. Mitochondrial respiration in permeabilized fibers, citrate synthase (CS) activity and protein expression of peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and respiratory complex components were measured. Results: HIT training improved peak power and time to fatigue. Increases in absolute oxidative phosphorylation (OXPHOS) capacities and CS activity were observed, but not in the ratio of CCO to the electron transport system (CCO/ETS), the respiratory control ratios (RCR-1 and RCR-2) or mitochondrial-associated protein expression. Specific increases in OXPHOS flux were not apparent after normalization to CS, indicating that gross changes mainly resulted from increased mitochondrial mass. Conclusion: Over only 2 weeks HIT significantly increased mitochondrial function in skeletal muscle independently of detectable changes in mitochondrial-associated and mitogenic protein expression. PMID:25759671

A genome-wide association study for equine recurrent airway obstruction in European Warmblood horses reveals a suggestive new quantitative trait locus on chromosome 13.

PubMed

Schnider, D; Rieder, S; Leeb, T; Gerber, V; Neuditschko, M

2017-12-01

Recurrent airway obstruction (RAO), also known as heaves, is an asthma-like respiratory disease. Its development is strongly influenced by environmental risk factors such as sensitization and exposure to moldy hay, straw bedding and stabling indoors. A hereditary component has been documented in previous studies; however, so far no causative genetic variant that influences the risk of developing RAO has been identified. In this study, we revised an existing dataset and selected 384 horses for genotyping on the Affymetrix high-density equine SNP array. We performed an allelic case-control genome-wide association study, which revealed a suggestively significant association on equine chromosome 13 at 32 843 309 bp. This SNP is located in the protein-coding gene TXNDC11, which is possibly involved in the folding process of the multiprotein complexes DUOX1 and DUOX2. In humans, these proteins are known to take part in regulating the production of H 2 O 2 in the respiratory tract epithelium as well as in MUC5AC mucin expression. Therefore, TXNDC11 may be considered a functional candidate gene, and further research is needed to explore its potential role in RAO-affected horses. © 2017 Stichting International Foundation for Animal Genetics.

Mitochondrial CHCHD-Containing Proteins: Physiologic Functions and Link with Neurodegenerative Diseases.

PubMed

Zhou, Zhi-Dong; Saw, Wuan-Ting; Tan, Eng-King

2017-09-01

The coiled-coil-helix-coiled-coil-helix domain (CHCHD)-containing proteins are evolutionarily conserved nucleus-encoded small mitochondrial proteins with important functions. So far, nine members have been identified in this protein family. All CHCHD proteins have at least one functional coiled-coil-helix-coiled-coil-helix (CHCH) domain, which is stabilized by two pairs of disulfide bonds between two helices. CHCHD proteins have various important pathophysiological roles in mitochondria and other key cellular processes. Mutations of CHCHD proteins have been associated with various human neurodegenerative diseases. Mutations of CHCHD10 are associated with amyotrophic lateral sclerosis (ALS) and/or frontotemporal lobe dementia (FTD), motor neuron disease, and late-onset spinal muscular atrophy and autosomal dominant mitochondrial myopathy. CHCHD10 stabilizes mitochondrial crista ultrastructure and maintains its integrity. In patients with CHCHD10 mutations, there are abnormal mitochondrial crista structure, deficiencies of respiratory chain complexes, impaired mitochondrial respiration, and multiple mitochondrial DNA (mtDNA) deletions. Recently, CHCHD2 mutations are linked with autosomal dominant and sporadic Parkinson's disease (PD). The CHCHD2 is a multifunctional protein and plays roles in regulation of mitochondrial metabolism, synthesis of respiratory chain components, and modulation of cell apoptosis. With a better understanding of the pathophysiologic roles of CHCHD proteins, they may be potential novel therapeutic targets for human neurodegenerative diseases.

Managing the cellular redox hub in photosynthetic organisms.

PubMed

Foyer, Christine H; Noctor, Graham

2012-02-01

Light-driven redox chemistry is a powerful source of redox signals that has a decisive input into transcriptional control within the cell nucleus. Like photosynthetic electron transport pathways, the respiratory electron transport chain exerts a profound control over gene function, in order to balance energy (reductant and ATP) supply with demand, while preventing excessive over-reduction or over-oxidation that would be adversely affect metabolism. Photosynthetic and respiratory redox chemistries are not merely housekeeping processes but they exert a controlling influence over every aspect of plant biology, participating in the control of gene transcription and translation, post-translational modifications and the regulation of assimilatory reactions, assimilate partitioning and export. The number of processes influenced by redox controls and signals continues to increase as do the components that are recognized participants in the associated signalling pathways. A step change in our understanding of the overall importance of the cellular redox hub to plant cells has occurred in recent years as the complexity of the management of the cellular redox hub in relation to metabolic triggers and environmental cues has been elucidated. This special issue describes aspects of redox regulation and signalling at the cutting edge of current research in this dynamic and rapidly expanding field. © 2011 Blackwell Publishing Ltd.

Analyzing symptom data in indoor air questionnaires for primary schools.

PubMed

Ung-Lanki, S; Lampi, J; Pekkanen, J

2017-09-01

Questionnaires on symptoms and perceived quality of indoor environment are used to assess indoor environment problems, but mainly among adults. The aim of this article was to explore best ways to analyze and report such symptom data, as part of a project to develop a parent-administered indoor air questionnaire for primary school pupils. Indoor air questionnaire with 25 questions on child's symptoms in the last 4 weeks was sent to parents in five primary schools with indoor air problems and in five control schools. About 83% of parents (N=1470) in case schools and 82% (N=805) in control schools returned the questionnaire. In two schools, 351 (52%) parents answered the questionnaire twice with a 2-week interval. Based on prevalence of symptoms, their test-retest repeatability (ICC), and on principal component analysis (PCA), the number of symptoms was reduced to 17 and six symptoms scores were developed. Six variants of these six symptom scores were then formed and their ability to rank schools compared. Four symptom scores (respiratory, lower respiratory, eye, and general symptoms) analyzed dichotomized maintained sufficiently well the diversity of symptom data and captured the between-school differences in symptom prevalence, when compared to more complex and numerous scores. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intracellular synthesis, processing, and transport of proteins encoded by ORFs 5 to 7 of porcine reproductive and respiratory syndrome virus.

PubMed

Mardassi, H; Massie, B; Dea, S

1996-07-01

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a small enveloped virus containing a positive-strand RNA genome, possesses at least three major structural proteins designated N, M, and E. The N protein is considered as the major component of the nucleocapsid, whereas M and E are membrane-associated. Previous studies using peptide-specific antibodies assigned these proteins to ORFs 7, 6, and 5, respectively. In the present report, monospecific antisera raised against Escherichia coli-expressed ORFs 5, 6, and 7 products were used to study the synthesis and processing of PRRSV structural proteins in the highly permissive MARC-145 cell line. Treatment of viral proteins with various glycosidases showed that only E was modified by N-linked glycans. Pulse-chase experiments revealed that intracellular transport of the major envelope glycoprotein was delayed in the premedial Golgi compartment. During the first 30 min of chase, E undergoes a gradual downward shift of its apparent molecular weight, thought to result from trimming of the mannose-rich glycan structures. Once E is transported to the medial Golgi or proximal elements, some molecules undergo complete processing of all their high-mannose N-linked oligosaccharides to complex type, while in other molecules only a fraction of N-linked glycans are terminally glycosylated. These two differentially glycosylated forms of E were found to be incorporated into extracellular virions. In cells and virions, both M and E were shown to occur in heterodimeric complexes linked by disulfide bonds. The oligomerization process, as analyzed from pulse-chase experiments, showed that M and E are incorporated into M-E complexes with different kinetics and efficiencies, in a fashion similar to their counterparts in equine arteritis virus. Apparently, all steps of E protein N-glycans processing proceed after its association with M which occurs in the endoplasmic reticulum (ER). In the infected cells, E and M appear highly membrane-associated, while N is predominantly cytosolic.

ATP transport through VDAC and the VDAC-tubulin complex probed by equilibrium and nonequilibrium MD simulations.

PubMed

Noskov, Sergei Yu; Rostovtseva, Tatiana K; Bezrukov, Sergey M

2013-12-23

Voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane, serves as a principal pathway for ATP, ADP, and other respiratory substrates across this membrane. Using umbrella-sampling simulations, we established the thermodynamic and kinetic components governing ATP transport across the VDAC1 channel. We found that there are several low-affinity binding sites for ATP along the translocation pathway and that the main barrier for ATP transport is located around the center of the channel and is formed predominantly by residues in the N-terminus. The binding affinity of ATP to an open channel was found to be in the millimolar to micromolar range. However, we show that this weak binding increases the ATP translocation probability by about 10-fold compared with the VDAC pore in which attractive interactions were artificially removed. Recently, it was found that free dimeric tubulin induces a highly efficient, reversible blockage of VDAC reconstituted into planar lipid membranes. It was proposed that by blocking VDAC permeability for ATP/ADP and other mitochondrial respiratory substrates tubulin controls mitochondrial respiration. Using the Rosetta protein-protein docking algorithm, we established a tentative structure of the VDAC-tubulin complex. An extensive set of equilibrium and nonequilibrium (under applied electric field) molecular dynamics (MD) simulations was used to establish the conductance of the open and blocked channel. It was found that the presence of the unstructured C-terminal tail of tubulin in the VDAC pore decreases its conductance by more than 40% and switches its selectivity from anionic to cationic. The subsequent 1D potential of mean force (PMF) computations for the VDAC-tubulin complex show that the state renders ATP transport virtually impossible. A number of residues pivotal for tubulin binding to the channel were identified that help to clarify the molecular details of VDAC-tubulin interaction and to provide new insight into the mechanism of the control of mitochondria respiration by VDAC.

42 CFR 84.86 - Component parts exposed to oxygen pressures; minimum requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Component parts exposed to oxygen pressures; minimum requirements. 84.86 Section 84.86 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY...

42 CFR 84.86 - Component parts exposed to oxygen pressures; minimum requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Component parts exposed to oxygen pressures; minimum requirements. 84.86 Section 84.86 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY...

42 CFR 84.111 - Gas masks; required components.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Gas masks; required components. 84.111 Section 84.111 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Gas Masks § 84...

42 CFR 84.111 - Gas masks; required components.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Gas masks; required components. 84.111 Section 84.111 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Gas Masks § 84...

42 CFR 84.86 - Component parts exposed to oxygen pressures; minimum requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Component parts exposed to oxygen pressures; minimum requirements. 84.86 Section 84.86 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY...

42 CFR 84.71 - Self-contained breathing apparatus; required components.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Self-contained breathing apparatus; required components. 84.71 Section 84.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...

42 CFR 84.71 - Self-contained breathing apparatus; required components.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Self-contained breathing apparatus; required components. 84.71 Section 84.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...

42 CFR 84.111 - Gas masks; required components.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Gas masks; required components. 84.111 Section 84.111 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Gas Masks § 84...

42 CFR 84.86 - Component parts exposed to oxygen pressures; minimum requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Component parts exposed to oxygen pressures; minimum requirements. 84.86 Section 84.86 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY...

42 CFR 84.111 - Gas masks; required components.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Gas masks; required components. 84.111 Section 84.111 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Gas Masks § 84...

42 CFR 84.111 - Gas masks; required components.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Gas masks; required components. 84.111 Section 84.111 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Gas Masks § 84...

42 CFR 84.71 - Self-contained breathing apparatus; required components.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Self-contained breathing apparatus; required components. 84.71 Section 84.71 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...

42 CFR 84.86 - Component parts exposed to oxygen pressures; minimum requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Component parts exposed to oxygen pressures; minimum requirements. 84.86 Section 84.86 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY...

Critically Ill Patients With the Middle East Respiratory Syndrome: A Multicenter Retrospective Cohort Study.

PubMed

Arabi, Yaseen M; Al-Omari, Awad; Mandourah, Yasser; Al-Hameed, Fahad; Sindi, Anees A; Alraddadi, Basem; Shalhoub, Sarah; Almotairi, Abdullah; Al Khatib, Kasim; Abdulmomen, Ahmed; Qushmaq, Ismael; Mady, Ahmed; Solaiman, Othman; Al-Aithan, Abdulsalam M; Al-Raddadi, Rajaa; Ragab, Ahmed; Al Mekhlafi, Ghaleb A; Al Harthy, Abdulrahman; Kharaba, Ayman; Ahmadi, Mashael Al; Sadat, Musharaf; Mutairi, Hanan Al; Qasim, Eman Al; Jose, Jesna; Nasim, Maliha; Al-Dawood, Abdulaziz; Merson, Laura; Fowler, Robert; Hayden, Frederick G; Balkhy, Hanan H

2017-10-01

To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. Retrospective cohort study. Patients admitted to ICUs in 14 Saudi Arabian hospitals. Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n = 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non-Middle East respiratory syndrome etiology (non-Middle East respiratory syndrome severe acute respiratory infection) (n = 222). None. Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non-Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78]; p < 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252]; p < 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7]; p = 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%; p < 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%; p = 0.003), vasopressor support (79.4% vs 55.0%; p < 0.001), and renal replacement therapy (48.8% vs 22.1%; p < 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non-Middle East respiratory syndrome severe acute respiratory infection (adjusted odds ratio, 5.87; 95% CI, 4.02-8.56; p < 0.001). Substantial overlap exists in the clinical presentation and comorbidities among patients with Middle East respiratory syndrome severe acute respiratory infection from other etiologies; therefore, a high index of suspicion combined with diagnostic testing is essential component of severe acute respiratory infection investigation for at-risk patients. The lack of distinguishing clinical features, the need to rely on real-time reverse transcription polymerase chain reaction from respiratory samples, variability in viral shedding duration, lack of effective therapy, and high mortality represent substantial clinical challenges and help guide ongoing clinical research efforts.

Analysis of epidemiological studies: facts and artifacts.

PubMed

Wright, Anne L

2002-09-01

Cohort studies have provided the foundation for much of our knowledge of childhood asthma. Four important lessons have been learned from these longitudinal studies: that asthma is a complex disease, encompassing many phenotypes; that it is linked to the development of the immune system and respiratory tract in the first years of life; that early life events strongly affect the development of asthma risk and that relationships between certain exposures and asthma risk are age dependent. The Tucson Children's Respiratory Study is used to exemplify these lessons and to illustrate the advantages of cohort studies in investigating a complex disease. Copyright 2002 Elsevier Science Ltd.

Cocaine- and amphetamine-regulated transcript peptide increases mitochondrial respiratory chain complex II activity and protects against oxygen-glucose deprivation in neurons.

PubMed

Sha, Dujuan; Wang, Luna; Zhang, Jun; Qian, Lai; Li, Qiming; Li, Jin; Qian, Jian; Gu, Shuangshuang; Han, Ling; Xu, Peng; Xu, Yun

2014-09-25

The mechanisms of ischemic stroke, a main cause of disability and death, are complicated. Ischemic stroke results from the interaction of various factors including oxidative stress, a key pathological mechanism that plays an important role during the acute stage of ischemic brain injury. This study demonstrated that cocaine- and amphetamine-regulated transcript (CART) peptide, specifically CART55-102, increased the survival rate, but decreased the mortality of neurons exposed to oxygen-glucose deprivation (OGD), in a dose-dependent manner. The above-mentioned effects of CART55-102 were most significant at 0.4nM. These results indicated that CART55-102 suppressed neurotoxicity and enhanced neuronal survival after oxygen-glucose deprivation. CART55-102 (0.4nM) significantly diminished reactive oxygen species levels and markedly increased the activity of mitochondrial respiratory chain complex II in oxygen-glucose deprived neurons. In summary, CART55-102 suppressed oxidative stress in oxygen-glucose deprived neurons, possibly through elevating the activity of mitochondrial respiratory chain complex II. This result provides evidence for the development of CART55-102 as an antioxidant drug. Copyright © 2014 Elsevier B.V. All rights reserved.

Observing the sick child: Part 2c. Respiratory auscultation.

PubMed

Aylott, Marion

2007-04-01

Nursing continues to extend its practice base as the acuity of children in general wards often with complex illnesses and treatment increases. There is a need for ongoing development of the physical assessment skills of nurses who care for children and young people in order to facilitate early recognition of clinical problems. Respiratory dysfunction is the common precursor to adverse events. The skill of auscultation adds another dimension that augments the respiratory assessment repertoire of the nurse. This article builds on the palpation skills presented in February issue and provides a practical step-by-step introduction to auscultation.

Stress-response transcription factors Msn2 and Msn4 couple TORC2-Ypk1 signaling and mitochondrial respiration to ATG8 gene expression and autophagy.

PubMed

Vlahakis, Ariadne; Lopez Muniozguren, Nerea; Powers, Ted

2017-01-01

Macroautophagy/autophagy is a starvation and stress-induced catabolic process critical for cellular homeostasis and adaptation. Several Atg proteins are involved in the formation of the autophagosome and subsequent degradation of cytoplasmic components, a process termed autophagy flux. Additionally, the expression of several Atg proteins, in particular Atg8, is modulated transcriptionally, yet the regulatory mechanisms involved remain poorly understood. Here we demonstrate that the AGC kinase Ypk1, target of the rapamycin-insensitive TORC2 signaling pathway, controls ATG8 expression by repressing the heterodimeric Zinc-finger transcription factors Msn2 and Msn4. We find that Msn2 and Msn4 promote ATG8 expression downstream of the histone deacetylase complex (HDAC) subunit Ume6, a previously identified negative regulator of ATG8 expression. Moreover, we demonstrate that TORC2-Ypk1 signaling is functionally linked to distinct mitochondrial respiratory complexes. Surprisingly, we find that autophagy flux during amino acid starvation is also dependent upon Msn2-Msn4 activity, revealing a broad role for these transcription factors in the autophagy response.

Tissue- and cell-type–specific manifestations of heteroplasmic mtDNA 3243A>G mutation in human induced pluripotent stem cell-derived disease model

PubMed Central

Hämäläinen, Riikka H.; Manninen, Tuula; Koivumäki, Hanna; Kislin, Mikhail; Otonkoski, Timo; Suomalainen, Anu

2013-01-01

Mitochondrial DNA (mtDNA) mutations manifest with vast clinical heterogeneity. The molecular basis of this variability is mostly unknown because the lack of model systems has hampered mechanistic studies. We generated induced pluripotent stem cells from patients carrying the most common human disease mutation in mtDNA, m.3243A>G, underlying mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. During reprogramming, heteroplasmic mtDNA showed bimodal segregation toward homoplasmy, with concomitant changes in mtDNA organization, mimicking mtDNA bottleneck during epiblast specification. Induced pluripotent stem cell–derived neurons and various tissues derived from teratomas manifested cell-type specific respiratory chain (RC) deficiency patterns. Similar to MELAS patient tissues, complex I defect predominated. Upon neuronal differentiation, complex I specifically was sequestered in perinuclear PTEN-induced putative kinase 1 (PINK1) and Parkin-positive autophagosomes, suggesting active degradation through mitophagy. Other RC enzymes showed normal mitochondrial network distribution. Our data show that cellular context actively modifies RC deficiency manifestation in MELAS and that autophagy is a significant component of neuronal MELAS pathogenesis. PMID:24003133

Potential bronchoconstrictor stimuli in acid fog.

PubMed Central

Balmes, J R; Fine, J M; Gordon, T; Sheppard, D

1989-01-01

Acid fog is complex and contains multiple stimuli that may be capable of inducing bronchoconstriction. These stimuli include sulfuric and niric acids, the principal inorganic acids present; sulfites, formed in the atmosphere as a reaction product of sulfur dioxide and water droplets; fog water itself, a hypoosmolar aerosol; the organic acid hydroxymethanesulfonate, the bisulfite adduct of formaldehyde; and gaseous pollutants, e.g., sulfur dioxide, oxides of nitrogen, ozone. Given this complexity, evaluation of the respiratory health effects of naturally occurring acid fog requires assessment of the bronchoconstrictor potency of each component stimulus and possible interactions among these stimuli. We summarize the results of three studies that involve characterization of the bronchoconstrictor potency of acid fog stimuli and/or their interaction in subjects with asthma. The results of the first study indicate that titratable acidity appears to be a more important stimulus to bronchoconstriction than is pH. The results of the second study demonstrate that sulfite species are capable of inducing bronchoconstriction, especially when inhaled at acid pH. The results of the third study suggest that acidity can potentiate hypoosmolar fog-induced bronchoconstriction. PMID:2539989

Hospital readmissions with acute infectious diseases in New Zealand children < 2 years of age.

PubMed

Seibt, Silvia; Gilchrist, Catherine A; Reed, Peter W; Best, Emma J; Harnden, Anthony; Camargo, Carlos A; Grant, Cameron C

2018-03-05

Infectious diseases are the leading cause of hospital admissions in young children. Hospitalisation with an infectious disease is a recurrent event for some children. Our objective was to describe risk factors for infectious disease readmission following hospital admission with an infectious disease in the first two years of life. We performed a national cohort study of New Zealand children, born 2005-2009, with an infectious disease admission before age 24 months. Children readmitted with an infectious disease within 12 months of the first infectious disease admission were identified. Every infectious disease admission was categorised as a respiratory, enteric, skin and soft tissue, urinary or other infection. Independent associations of demographic and child health factors with infectious disease readmission were determined using multiple variable logistic regression. From 2005 to 2011, there were 69,902 infectious disease admissions for 46,657 children less than two years old. Of these 46,657 children, 10,205 (22%) had at least one infectious disease readmission within 12 months of their first admission. The first infectious disease admission was respiratory (54%), enteric (15%), skin or soft tissue (7%), urinary (4%) or other (20%). Risk of infectious disease readmission was increased if the first infectious disease admission was respiratory (OR = 1.87, 95% CI 1.78-1.95) but not if it was in any other infectious disease category. Risk factors for respiratory infectious disease readmission were male gender, Pacific or Māori ethnicity, greater household deprivation, presence of a complex chronic condition, or a first respiratory infectious disease admission during autumn or of ≥3 days duration. Fewer factors (younger age, male gender, presence of a complex chronic condition) were associated with enteric infection readmission. The presence of a complex chronic condition was the only factor associated with urinary tract infection readmission and none of the factors were associated with skin or soft tissue infection readmission. In children less than two years old, infectious disease readmission risk is increased if the first infectious disease admission is a respiratory infectious disease but not if it is another infectious disease category. Risk factors for respiratory infectious disease readmission are different from those for other infectious disease readmissions.

A mouse model of mitochondrial complex III dysfunction induced by myxothiazol

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

Davoudi, Mina; Kallijärvi, Jukka; Marjavaara, Sanna

2014-04-18

Highlights: • Reversible chemical inhibition of complex III in wild type mouse. • Myxothiazol causes decreased complex III activity in mouse liver. • The model is useful for therapeutic trials to improve mitochondrial function. - Abstract: Myxothiazol is a respiratory chain complex III (CIII) inhibitor that binds to the ubiquinol oxidation site Qo of CIII. It blocks electron transfer from ubiquinol to cytochrome b and thus inhibits CIII activity. It has been utilized as a tool in studies of respiratory chain function in in vitro and cell culture models. We developed a mouse model of biochemically induced and reversible CIIImore » inhibition using myxothiazol. We administered myxothiazol intraperitoneally at a dose of 0.56 mg/kg to C57Bl/J6 mice every 24 h and assessed CIII activity, histology, lipid content, supercomplex formation, and gene expression in the livers of the mice. A reversible CIII activity decrease to 50% of control value occurred at 2 h post-injection. At 74 h only minor histological changes in the liver were found, supercomplex formation was preserved and no significant changes in the expression of genes indicating hepatotoxicity or inflammation were found. Thus, myxothiazol-induced CIII inhibition can be induced in mice for four days in a row without overt hepatotoxicity or lethality. This model could be utilized in further studies of respiratory chain function and pharmacological approaches to mitochondrial hepatopathies.« less

Reprogramming of leukemic cell metabolism through the naphthoquinonic compound Quambalarine B

PubMed Central

Vališ, Karel; Grobárová, Valéria; Hernychová, Lucie; Bugáňová, Martina; Kavan, Daniel; Kalous, Martin; Černý, Jiří; Stodůlková, Eva; Kuzma, Marek; Flieger, Miroslav; Černý, Jan; Novák, Petr

2017-01-01

Abnormalities in cancer metabolism represent potential targets for cancer therapy. We have recently identified a natural compound Quambalarine B (QB), which inhibits proliferation of several leukemic cell lines followed by cell death. We have predicted ubiquinone binding sites of mitochondrial respiratory complexes as potential molecular targets of QB in leukemia cells. Hence, we tracked the effect of QB on leukemia metabolism by applying several omics and biochemical techniques. We have confirmed the inhibition of respiratory complexes by QB and found an increase in the intracellular AMP levels together with respiratory substrates. Inhibition of mitochondrial respiration by QB triggered reprogramming of leukemic cell metabolism involving disproportions in glycolytic flux, inhibition of proteins O-glycosylation, stimulation of glycine synthesis pathway, and pyruvate kinase activity, followed by an increase in pyruvate and a decrease in lactate levels. Inhibition of mitochondrial complex I by QB suppressed folate metabolism as determined by a decrease in formate production. We have also observed an increase in cellular levels of several amino acids except for aspartate, indicating the dependence of Jurkat (T-ALL) cells on aspartate synthesis. These results indicate blockade of mitochondrial complex I and II activity by QB and reduction in aspartate and folate metabolism as therapeutic targets in T-ALL cells. Anti-cancer activity of QB was also confirmed during in vivo studies, suggesting the therapeutic potential of this natural compound. PMID:29262552

Lung Disease Associated With Marijuana Use.

PubMed

Chatkin, José Miguel; Zabert, Gustavo; Zabert, Ignacio; Chatkin, Gustavo; Jiménez-Ruiz, Carlos Andrés; de Granda-Orive, Jose Ignacio; Buljubasich, Daniel; Solano Reina, Segismundo; Figueiredo, Ana; Ravara, Sofia; Riesco Miranda, Juan Antonio; Gratziou, Christina

2017-09-01

Marijuana is the most widely usedillegal drug in the world, with a prevalence of 2.5%-5%, and the second most commonly smoked substance after tobacco. The components of smoke from combustion of marijuana are similar to those produced by the combustion of tobacco, but they differ in terms of psychoactive components and use. Inhalation of cannabis smoke affects the respiratory tract, so the available evidence must be updated in order to provide pulmonologists with the latest scientific information. In this article, we review the impact of cannabis consumption on the lungs, taking into account that the respiratory route is the most popular route of cannabis consumption. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Disruption of the cytochrome c gene in xylose-utilizing yeast Pichia stipitis leads to higher ethanol production

Treesearch

Nian-Qing Shi; Brian Davis; Fred Sherman; Jose Cruz; Thomas W. Jeffries

1999-01-01

The xylose-utilizing yeast, Pichia stipitis, has a complex respiratory system that contains cytochrome and non-cytochrome alternative electron transport chains in its mitochondria. To gain primary insights into the alternative respiratory pathway, a cytochrome c gene (PsCYC1, Accession No. AF030426) was cloned from wild-type P. stipitis CBS 6054 by cross-hybridization...

Three-dimensional analysis of the respiratory interplay effect in helical tomotherapy: Baseline variations cause the greater part of dose inhomogeneities seen.

PubMed

Tudor, G Samuel J; Harden, Susan V; Thomas, Simon J

2014-03-01

Dose differences from those planned can occur due to the respiratory interplay effect on helical tomotherapy. The authors present a technique to calculate single-fraction doses in three-dimensions resulting from craniocaudal motion applied to a patient CT set. The technique is applied to phantom and patient plans using patient respiratory traces. An additional purpose of the work is to determine the contribution toward the interplay effect of different components of the respiratory trace. MATLAB code used to calculate doses to a CT dataset from a helical tomotherapy plan has been modified to permit craniocaudal motion and improved temporal resolution. Real patient traces from seven patients were applied to ten phantom plans of differing field width, modulation factor, pitch and fraction dose, and simulations made with peak-to-peak amplitudes ranging from 0 to 2.5 cm. PTV voxels near the superior or inferior limits of the PTV are excluded from the analysis. The maximum dose discrepancy compared with the static case recorded along with the proportion of voxels receiving more than 10% and 20% different from prescription dose. The analysis was repeated with the baseline variation of the respiratory trace removed, leaving the cyclic component of motion only. Radiochromic film was used on one plan-trace combination and compared with the software simulation. For one case, filtered traces were generated and used in simulations which consisted only of frequencies near to particular characteristic frequencies of the treatment delivery. Intraslice standard deviation of dose differences was used to identify potential MLC interplay, which was confirmed using nonmodulated simulations. Software calculations were also conducted for four realistic patient plans and modeling movement of a patient CT set with amplitudes informed by the observed motion of the GTV on 4DCT. The maximum magnitude of dose difference to a PTV voxel due to the interplay effect within a particular plan-trace combination for peak-to-peak amplitudes of up to 2.5 cm ranged from 4.5% to 51.6% (mean: 23.8%) of the dose delivered in the absence of respiratory motion. For cyclic motion only, the maximum dose differences in each combination ranged from 2.1% to 26.2% (mean: 9.2%). There is reasonable correspondence between an example of the phantom plan simulations and radiochromic film measurement. The filtered trace simulations revealed that frequencies close to the characteristic frequency of the jaw motion across the target were found to generate greater interplay effect than frequencies close to the gantry frequency or MLC motion. There was evidence of interplay between respiratory motion and MLC modulation, but this is small compared with the interplay between respiratory motion and jaw motion. For patient-plan simulations, dose discrepancies are seen of up to 9.0% for a patient with 0.3 cm peak-to-peak respiratory amplitude and up to 17.7% for a patient with 0.9 cm peak-to-peak amplitude. These values reduced to 1.3% and 6.5%, respectively, when only cyclic motion was considered. Software has been developed to simulate craniocaudal respiratory motion in phantom and patient plans using real patient respiratory traces. Decomposition of the traces into baseline andcyclic components reveals that the large majority of the interplay effect seen with the full trace is due to baseline variation during treatment.

Genome Analysis of Structure–Function Relationships in Respiratory Complex I, an Ancient Bioenergetic Enzyme

PubMed Central

Degli Esposti, Mauro

2016-01-01

Respiratory complex I (NADH:ubiquinone oxidoreductase) is a ubiquitous bioenergetic enzyme formed by over 40 subunits in eukaryotes and a minimum of 11 subunits in bacteria. Recently, crystal structures have greatly advanced our knowledge of complex I but have not clarified the details of its reaction with ubiquinone (Q). This reaction is essential for bioenergy production and takes place in a large cavity embedded within a conserved module that is homologous to the catalytic core of Ni–Fe hydrogenases. However, how a hydrogenase core has evolved into the protonmotive Q reductase module of complex I has remained unclear. This work has exploited the abundant genomic information that is currently available to deduce structure–function relationships in complex I that indicate the evolutionary steps of Q reactivity and its adaptation to natural Q substrates. The results provide answers to fundamental questions regarding various aspects of complex I reaction with Q and help re-defining the old concept that this reaction may involve two Q or inhibitor sites. The re-definition leads to a simplified classification of the plethora of complex I inhibitors while throwing a new light on the evolution of the enzyme function. PMID:26615219

Influence of physical fitness on cardio-metabolic risk factors in European children. The IDEFICS study.

PubMed

Zaqout, M; Michels, N; Bammann, K; Ahrens, W; Sprengeler, O; Molnar, D; Hadjigeorgiou, C; Eiben, G; Konstabel, K; Russo, P; Jiménez-Pavón, D; Moreno, L A; De Henauw, S

2016-07-01

The aim of the study was to assess the associations of individual and combined physical fitness components with single and clustering of cardio-metabolic risk factors in children. This 2-year longitudinal study included a total of 1635 European children aged 6-11 years. The test battery included cardio-respiratory fitness (20-m shuttle run test), upper-limb strength (handgrip test), lower-limb strength (standing long jump test), balance (flamingo test), flexibility (back-saver sit-and-reach) and speed (40-m sprint test). Metabolic risk was assessed through z-score standardization using four components: waist circumference, blood pressure (systolic and diastolic), blood lipids (triglycerides and high-density lipoprotein) and insulin resistance (homeostasis model assessment). Mixed model regression analyses were adjusted for sex, age, parental education, sugar and fat intake, and body mass index. Physical fitness was inversely associated with clustered metabolic risk (P<0.001). All coefficients showed a higher clustered metabolic risk with lower physical fitness, except for upper-limb strength (β=0.057; P=0.002) where the opposite association was found. Cardio-respiratory fitness (β=-0.124; P<0.001) and lower-limb strength (β=-0.076; P=0.002) were the most important longitudinal determinants. The effects of cardio-respiratory fitness were even independent of the amount of vigorous-to-moderate activity (β=-0.059; P=0.029). Among all the metabolic risk components, blood pressure seemed not well predicted by physical fitness, while waist circumference, blood lipids and insulin resistance all seemed significantly predicted by physical fitness. Poor physical fitness in children is associated with the development of cardio-metabolic risk factors. Based on our results, this risk might be modified by improving mainly cardio-respiratory fitness and lower-limb muscular strength.

Abdominal expiratory activity in the rat brainstem–spinal cord in situ: patterns, origins and implications for respiratory rhythm generation

PubMed Central

Abdala, A P L; Rybak, I A; Smith, J C; Paton, J F R

2009-01-01

We studied respiratory neural activity generated during expiration. Motoneuronal activity was recorded simultaneously from abdominal (AbN), phrenic (PN), hypoglossal (HN) and central vagus nerves from neonatal and juvenile rats in situ. During eupnoeic activity, low-amplitude post-inspiratory (post-I) discharge was only present in AbN motor outflow. Expression of AbN late-expiratory (late-E) activity, preceding PN bursts, occurred during hypercapnia. Biphasic expiratory (biphasic-E) activity with pre-inspiratory (pre-I) and post-I discharges occurred only during eucapnic anoxia or hypercapnic anoxia. Late-E activity generated during hypercapnia (7–10% CO2) was abolished with pontine transections or chemical suppression of retrotrapezoid nucleus/ventrolateral parafacial (RTN/vlPF). AbN late-E activity during hypercapnia is coupled with augmented pre-I discharge in HN, truncated PN burst, and was quiescent during inspiration. Our data suggest that the pons provides a necessary excitatory drive to an additional neural oscillatory mechanism that is only activated under conditions of high respiratory drive to generate late-E activity destined for AbN motoneurones. This mechanism may arise from neurons located in the RTN/vlPF or the latter may relay late-E activity generated elsewhere. We hypothesize that this oscillatory mechanism is not a necessary component of the respiratory central pattern generator but constitutes a defensive mechanism activated under critical metabolic conditions to provide forced expiration and reduced upper airway resistance simultaneously. Possible interactions of this oscillator with components of the brainstem respiratory network are discussed. PMID:19491247

Bordetella bronchiseptica exploits the complex life cycle of Dictyostelium discoideum as an amplifying transmission vector

PubMed Central

Linz, Bodo; Rivera, Israel; Ryman, Valerie E.; Dewan, Kalyan K.; Wagner, Shannon M.; Wilson, Emily F.; Hilburger, Lindsay J.; Cuff, Laura E.; West, Christopher M.; Harvill, Eric T.

2017-01-01

Multiple lines of evidence suggest that Bordetella species have a significant life stage outside of the mammalian respiratory tract that has yet to be defined. The Bordetella virulence gene (BvgAS) two-component system, a paradigm for a global virulence regulon, controls the expression of many “virulence factors” expressed in the Bvg positive (Bvg+) phase that are necessary for successful respiratory tract infection. A similarly large set of highly conserved genes are expressed under Bvg negative (Bvg-) phase growth conditions; however, these appear to be primarily expressed outside of the host and are thus hypothesized to be important in an undefined extrahost reservoir. Here, we show that Bvg- phase genes are involved in the ability of Bordetella bronchiseptica to grow and disseminate via the complex life cycle of the amoeba Dictyostelium discoideum. Unlike bacteria that serve as an amoeba food source, B. bronchiseptica evades amoeba predation, survives within the amoeba for extended periods of time, incorporates itself into the amoeba sori, and disseminates along with the amoeba. Remarkably, B. bronchiseptica continues to be transferred with the amoeba for months, through multiple life cycles of amoebae grown on the lawns of other bacteria, thus demonstrating a stable relationship that allows B. bronchiseptica to expand and disperse geographically via the D. discoideum life cycle. Furthermore, B. bronchiseptica within the sori can efficiently infect mice, indicating that amoebae may represent an environmental vector within which pathogenic bordetellae expand and disseminate to encounter new mammalian hosts. These data identify amoebae as potential environmental reservoirs as well as amplifying and disseminating vectors for B. bronchiseptica and reveal an important role for the Bvg- phase in these interactions. PMID:28403138

A cascade of Ca2+/calmodulin-dependent protein kinases regulates the differentiation and functional activation of murine neutrophils

PubMed Central

Gaines, Peter; Lamoureux, James; Marisetty, Anantha; Chi, Jeffrey; Berliner, Nancy

2008-01-01

Objective The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the NADPH oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex network of intracellular signaling pathways. In this study we have investigated the role of two members of the calcium/calmodulin-dependent protein kinase (CaMK) signaling cascade, CaMKI-like kinase (CKLiK) and CaMKKα, in regulating neutrophil differentiation and functional activation. Materials and Methods Mouse myeloid cell lines were used to examine the expression of a CaMK cascade in developing neutrophils and to examine the effects of constitutive activation versus inhibition of CaMKs on neutrophil maturation. Results Expression of CaMKKα was shown to increase during neutrophil differentiation in multiple cell lines, whereas expression of CKLiK increased as multipotent progenitors committed to promyelocytes but then decreased as cells differentiated into mature neutrophils. Expression of constitutively active CKLiKs did not affect morphologic maturation, but caused dramatic decreases in both respiratory burst responses and chemotaxis. This loss of neutrophil function was accompanied by reduced secondary granule and gp91phox gene expression. The CaMK inhibitor KN93 attenuated cytokine-stimulated proliferative responses in promyelocytic cell lines, and inhibited the respiratory burst. Similar data were observed with the CaMKKα inhibitor, STO-609. Conclusions Overactivation of a cascade of CaMKs inhibits neutrophil maturation, suggesting that these kinases play an antagonistic role during neutrophil differentiation, but at least one CaMK is required for myeloid cell expansion and functional activation. PMID:18400360

The general mitochondrial processing peptidase from potato is an integral part of cytochrome c reductase of the respiratory chain.

PubMed Central

Braun, H P; Emmermann, M; Kruft, V; Schmitz, U K

1992-01-01

The major mitochondrial processing activity removing presequences from nuclear encoded precursor proteins is present in the soluble fraction of fungal and mammalian mitochondria. We found that in potato, this activity resides in the inner mitochondrial membrane. Surprisingly, the proteolytic activity co-purifies with cytochrome c reductase, a protein complex of the respiratory chain. The purified complex is bifunctional, as it has the ability to transfer electrons from ubiquinol to cytochrome c and to cleave off the presequences of mitochondrial precursor proteins. In contrast to the nine subunit fungal complex, cytochrome c reductase from potato comprises 10 polypeptides. Protein sequencing of peptides from individual subunits and analysis of corresponding cDNA clones reveals that subunit III of cytochrome c reductase (51 kDa) represents the general mitochondrial processing peptidase. Images PMID:1324169

21 CFR 520.2170 - Sulfabromomethazine sodium boluses.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Section 520.2170 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... pound body weight. (2) Indications for use. Treatment of necrotic pododermatitis (foot rot) and calf... pneumonia and bovine respiratory disease complex (shipping fever complex) associated with Pasteurella spp...

21 CFR 520.2170 - Sulfabromomethazine sodium boluses.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Section 520.2170 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... pound body weight. (2) Indications for use. Treatment of necrotic pododermatitis (foot rot) and calf... pneumonia and bovine respiratory disease complex (shipping fever complex) associated with Pasteurella spp...

Comprehensive mathematical model of oxidative phosphorylation valid for physiological and pathological conditions.

PubMed

Heiske, Margit; Letellier, Thierry; Klipp, Edda

2017-09-01

We developed a mathematical model of oxidative phosphorylation (OXPHOS) that allows for a precise description of mitochondrial function with respect to the respiratory flux and the ATP production. The model reproduced flux-force relationships under various experimental conditions (state 3 and 4, uncoupling, and shortage of respiratory substrate) as well as time courses, exhibiting correct P/O ratios. The model was able to reproduce experimental threshold curves for perturbations of the respiratory chain complexes, the F 1 F 0 -ATP synthase, the ADP/ATP carrier, the phosphate/OH carrier, and the proton leak. Thus, the model is well suited to study complex interactions within the OXPHOS system, especially with respect to physiological adaptations or pathological modifications, influencing substrate and product affinities or maximal catalytic rates. Moreover, it could be a useful tool to study the role of OXPHOS and its capacity to compensate or enhance physiopathologies of the mitochondrial and cellular energy metabolism. © 2017 Federation of European Biochemical Societies.

Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

PubMed

Gershwin, Laurel J; Van Eenennaam, Alison L; Anderson, Mark L; McEligot, Heather A; Shao, Matt X; Toaff-Rosenstein, Rachel; Taylor, Jeremy F; Neibergs, Holly L; Womack, James

2015-01-01

Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex

PubMed Central

Gershwin, Laurel J.; Van Eenennaam, Alison L.; Anderson, Mark L.; McEligot, Heather A.; Toaff-Rosenstein, Rachel; Taylor, Jeremy F.; Neibergs, Holly L.; Womack, James

2015-01-01

Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described. PMID:26571015

Identification of small non-coding RNA classes expressed in swine whole blood during HP-PRRSV infection

USDA-ARS?s Scientific Manuscript database

It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

42 CFR 84.12 - Delivery of respirators and components by applicant; requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 1 2010-10-01 2010-10-01 false Delivery of respirators and components by applicant; requirements. 84.12 Section 84.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES...

42 CFR 84.12 - Delivery of respirators and components by applicant; requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 1 2011-10-01 2011-10-01 false Delivery of respirators and components by applicant; requirements. 84.12 Section 84.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES...

42 CFR 84.12 - Delivery of respirators and components by applicant; requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 1 2013-10-01 2013-10-01 false Delivery of respirators and components by applicant; requirements. 84.12 Section 84.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES...

42 CFR 84.12 - Delivery of respirators and components by applicant; requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 1 2014-10-01 2014-10-01 false Delivery of respirators and components by applicant; requirements. 84.12 Section 84.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES...

42 CFR 84.12 - Delivery of respirators and components by applicant; requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 1 2012-10-01 2012-10-01 false Delivery of respirators and components by applicant; requirements. 84.12 Section 84.12 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES...

Involvement of the raphe in the respiratory effects of gigantocellular area activation.

PubMed

Richard, C A; Stremel, R W

1990-07-01

Previous reports indicate that the nucleus reticularis gigantocellularis (NGC) of the brainstem reticular formation is involved in inhibitory respiratory and cardiovascular reflexes. Stimulation of portions of the nearby bulbar raphe complex, specifically the raphe magnus (RM), have also been shown to suppress phrenic activity and to decrease blood pressure and heart rate. Since synaptic connectivity between the NGC and the RM has been demonstrated, we hypothesized that the RM may be involved in the cardiopulmonary effects of NGC stimulation. This study found that electrolytic lesions in the raphe magnus attenuated the inhibitory respiratory effects but not the cardiovascular suppression due to NGC stimulation. Lesions in the raphe magnus also lowered resting blood pressure and resting breath frequency. We conclude that the RM may mediate part of the NGC-mediated respiratory effects.

Respiratory exacerbation in a young adult with cystic fibrosis and tricuspid atresia.

PubMed

Wood, Jamie; Sawyer, Abbey; Mulrennan, Siobhain; Bullock, Andrew

2018-07-01

Tricuspid atresia (TAt) is a complex congenital heart defect (CHD) characterized by the absence of the tricuspid valve and right ventricular hypoplasia requiring surgery in childhood, the Fontan procedure. We present a case of a 21-year-old male with TAt and cystic fibrosis (CF), who underwent a Fontan procedure in childhood, presenting to an adult CF clinic with severe deterioration in his respiratory status and multi-organ dysfunction associated with CF. This report describes problems associated with the management of a CF respiratory exacerbation and extrapulmonary manifestations of CF in the unique situation of a Fontan circulation, a circulation with absence of a subpulmonary ventricle and pulsatile pulmonary arterial blood flow where maintenance of systemic cardiac output is totally dependent on good respiratory function and low pulmonary artery pressures.

Respiratory Pathways Reconstructed by Multi-Omics Analysis in Melioribacter roseus, Residing in a Deep Thermal Aquifer of the West-Siberian Megabasin

PubMed Central

Gavrilov, Sergey; Podosokorskaya, Olga; Alexeev, Dmitry; Merkel, Alexander; Khomyakova, Maria; Muntyan, Maria; Altukhov, Ilya; Butenko, Ivan; Bonch-Osmolovskaya, Elizaveta; Govorun, Vadim; Kublanov, Ilya

2017-01-01

Melioribacter roseus, a representative of recently proposed Ignavibacteriae phylum, is a metabolically versatile thermophilic bacterium, inhabiting subsurface biosphere of the West-Siberian megabasin and capable of growing on various substrates and electron acceptors. Genomic analysis followed by inhibitor studies and membrane potential measurements of aerobically grown M. roseus cells revealed the activity of aerobic respiratory electron transfer chain comprised of respiratory complexes I and IV, and an alternative complex III. Phylogeny reconstruction revealed that oxygen reductases belonged to atypical cc(o/b)o3-type and canonical cbb3–type cytochrome oxidases. Also, two molybdoenzymes of M. roseus were affiliated either with Ttr or Psr/Phs clades, but not with typical respiratory arsenate reductases of the Arr clade. Expression profiling, both at transcripts and protein level, allowed us to assign the role of the terminal respiratory oxidase under atmospheric oxygen concentration for the cc(o/b)o3 cytochrome oxidase, previously proposed to serve for oxygen detoxification only. Transcriptomic analysis revealed the involvement of both molybdoenzymes of M. roseus in As(V) respiration, yet differences in the genomic context of their gene clusters allow to hypothesize about their distinct roles in arsenate metabolism with the ‘Psr/Phs’-type molybdoenzyme being the most probable candidate respiratory arsenate reductase. Basing on multi-omics data, the pathways for aerobic and arsenate respiration were proposed. Our results start to bridge the vigorously increasing gap between homology-based predictions and experimentally verified metabolic processes, what is especially important for understudied microorganisms of novel lineages from deep subsurface environments of Eurasia, which remained separated from the rest of the biosphere for several geological periods. PMID:28713355

Partitioning of electron flux between the respiratory chains of the yeast Candida parapsilosis: parallel working of the two chains.

PubMed

Guerin, M G; Camougrand, N M

1994-02-08

Partitioning of the electron flux between the classical and the alternative respiratory chains of the yeast Candida parapsilosis, was measured as a function of the oxidation rate and of the Q-pool redox poise. At low respiration rate, electrons from external NADH travelled preferentially through the alternative pathway as indicated by the antimycin A-insensitivity of electron flow. Inhibition of the alternative pathway by SHAM restored full antimycin A-sensitivity to the remaining electro flow. The dependence of the respiratory rate on the redox poise of the quinone pool was investigated when the electron flux was mediated either by the main respiratory chain (growth in the absence of antimycin A) or by the second respiratory chain (growth in the presence of antimycin A). In the former case, a linear relationship was found between these two parameters. In contrast, in the latter case, the relationship between Q-pool reduction level and electron flux was non-linear, but it could be resolved into two distinct curves. This second quinone is not reducible in the presence of antimycin A but only in the presence of high concentrations of myxothiazol or cyanide. Since two quinone species exist in C. parapsilosis, UQ9 and Qx (C33H54O4), we hypothesized that these two curves could correspond to the functioning of the second quinone engaged during the alternative pathway activity. Partitioning of electrons between both respiratory chains could occur upstream of complex III with the second chain functioning in parallel to the main one, and with the additional possibility of merging into the main one at the complex IV level.

Nicotine and elevated body temperature reduce the complexity of the genioglossus and diaphragm EMG signals in rats during early maturation

NASA Astrophysics Data System (ADS)

Akkurt, David; Akay, Yasemin M.; Akay, Metin

2009-10-01

In this paper, we examined the effect of nicotine exposure and increased body temperature on the complexity (dynamics) of the genioglossus muscle (EMGg) and the diaphragm muscle (EMGdia) to explore the effects of nicotine and hyperthermia. Nonlinear dynamical analysis of the EMGdia and EMGg signals was performed using the approximate entropy method on 15 (7 saline- and 8 nicotine-treated) juvenile rats (P25-P35) and 19 (11 saline- and 8 nicotine-treated) young adult rats (P36-P44). The mean complexity values were calculated over the ten consecutive breaths using the approximate entropy method during mild elevated body temperature (38 °C) and severe elevated body temperature (39-40 °C) in two groups. In the first (nicotine) group, rats were treated with single injections of nicotine enough to produce brain levels of nicotine similar to those achieved in human smokers (2.5 (mg kg-1)/day) until the recording day. In the second (control) group, rats were treated with injections of saline, beginning at postnatal 5 days until the recording day. Our results show that warming the rat by 2-3 °C and nicotine exposure significantly decreased the complexity of the EMGdia and EMGg for the juvenile age group. This reduction in the complexity of the EMGdia and EMGg for the nicotine group was much greater than the normal during elevated body temperatures. We speculate that the generalized depressive effects of nicotine exposure and elevated body temperature on the respiratory neural firing rate and the behavior of the central respiratory network could be responsible for the drastic decrease in the complexity of the EMGdia and EMGg signals, the outputs of the respiratory neural network during early maturation.

Comparison of Four Commercial One-Dose Porcine Circovirus Type 2 (PCV2) Vaccines Administered to Pigs Challenged with PCV2 and Porcine Reproductive and Respiratory Syndrome Virus at 17 Weeks Postvaccination To Control Porcine Respiratory Disease Complex under Korean Field Conditions

PubMed Central

Park, Changhoon; Seo, Hwi Won; Han, Kiwon

2014-01-01

Under Korean field conditions, coinfection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is most commonly observed in porcine respiratory disease complex (PRDC). Despite the wide use of PCV2 vaccination, PRDC remains a serious respiratory problem. Thus, the objective of this study was to determine and compare the efficacy of 4 one-dose PCV2 vaccines on 3-week-old pigs with an experimental PCV2-PRRSV challenge at 17 weeks postvaccination. Regardless of which commercial PCV2 vaccine was used, the vaccination of piglets at 3 weeks of age was efficacious against cochallenge of PCV2 and PRRSV, on the basis of growth performance and PCV2-associated lesions. However, the inactivated chimeric PCV1-2 and the PCV2 vaccines induced higher PCV2-specific neutralizing antibody (NA) titers and PCV2-specific gamma interferon-secreting cells and lower PCV2 viremia levels than the two PCV2 subunit vaccines. The vaccination of piglets against PCV2 at 3 weeks of age was effective in reducing PCV2 viremia and PCV2-associated lesions during the finishing period, which is an age at which pigs are frequently affected by PRDC caused by coinfection with PCV2 and PRRSV under Korean field conditions. PMID:24403524

Comparison of four commercial one-dose porcine circovirus type 2 (PCV2) vaccines administered to pigs challenged with PCV2 and porcine reproductive and respiratory syndrome virus at 17 weeks postvaccination to control porcine respiratory disease complex under Korean field conditions.

PubMed

Park, Changhoon; Seo, Hwi Won; Han, Kiwon; Chae, Chanhee

2014-03-01

Under Korean field conditions, coinfection with porcine circovirus type 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRSV) is most commonly observed in porcine respiratory disease complex (PRDC). Despite the wide use of PCV2 vaccination, PRDC remains a serious respiratory problem. Thus, the objective of this study was to determine and compare the efficacy of 4 one-dose PCV2 vaccines on 3-week-old pigs with an experimental PCV2-PRRSV challenge at 17 weeks postvaccination. Regardless of which commercial PCV2 vaccine was used, the vaccination of piglets at 3 weeks of age was efficacious against cochallenge of PCV2 and PRRSV, on the basis of growth performance and PCV2-associated lesions. However, the inactivated chimeric PCV1-2 and the PCV2 vaccines induced higher PCV2-specific neutralizing antibody (NA) titers and PCV2-specific gamma interferon-secreting cells and lower PCV2 viremia levels than the two PCV2 subunit vaccines. The vaccination of piglets against PCV2 at 3 weeks of age was effective in reducing PCV2 viremia and PCV2-associated lesions during the finishing period, which is an age at which pigs are frequently affected by PRDC caused by coinfection with PCV2 and PRRSV under Korean field conditions.

Are minidisc recorders adequate for the study of respiratory sounds?

PubMed

Kraman, Steve S; Wodicka, George R; Kiyokawa, Hiroshi; Pasterkamp, Hans

2002-01-01

Digital audio tape (DAT) recorders have become the de facto gold standard recording devices for lung sounds. Sound recorded on DAT is compact-disk (CD) quality with adequate sensitivity from below 20 Hz to above 20 KHz. However, DAT recorders have drawbacks. Although small, they are relatively heavy, the recording mechanism is complex and delicate, and finding one desired track out of many is inconvenient. A more recent development in portable recording devices is the minidisc (MD) recorder. These recorders are widely available, inexpensive, small and light, rugged, mechanically simple, and record digital data in tracks that may be named and accessed directly. Minidiscs hold as much recorded sound as a compact disk but in about 1/5 of the recordable area. The data compression is achieved by use of a technique known as adaptive transform acoustic coding for minidisc (ATRAC). This coding technique makes decisions about what components of the sound would not be heard by a human listener and discards the digital information that represents these sounds. Most of this compression takes place on sounds above 5.5 KHz. As the intended use of these recorders is the storage and reproduction of music, it is unknown whether ATRAC will discard or distort significant portions of typical lung sound signals. We determined the suitability of MD recorders for respiratory sound research by comparing a variety of normal and pathologic lung sounds that were digitized directly into a computer and also after recording by a DAT recorder and 2 different MD recorders (Sharp and Sony). We found that the frequency spectra and waveforms of respiratory sounds were not distorted in any important way by recording on the two MD recorders tested.

The role of respiratory measures to assess mental load in pilot selection.

PubMed

Grassmann, Mariel; Vlemincx, Elke; von Leupoldt, Andreas; Van den Bergh, Omer

2016-06-01

While cardiovascular measures have a long tradition of being used to determine operator load, responsiveness of the respiratory system to mental load has rarely been investigated. In this study, we assessed basic and variability measures of respiration rate (RR), partial pressure of end-tidal carbon dioxide (petCO2) as well as performance measures in 63 male pilot candidates during completion of a complex cognitive task and subsequent recovery. Mental load was associated with an increase in RR and a decrease in respiratory variability. A significant decrease was also found for petCO2. RR and respiratory variability showed partial and complete effects of recovery, respectively, whereas petCO2 did not return to baseline level. Overall, a good performance was related to a stronger reactivity in RR. Our findings suggest that respiratory parameters would be a useful supplement to common measures for the assessment of mental load in pilot selection. Practitioner Summary: Respiratory measures are a promising yet poorly investigated approach to monitor operator load. For pilot selection, we assessed respiration in response to multitasking in 63 candidates. Task-related changes as well as covariation with performance strongly support the consideration of respiratory parameters when evaluating reactivity to mental load.

Biomarker as a Research Tool in Linking Exposure to Air Particles and Respiratory Health

PubMed Central

2015-01-01

Some of the environmental toxicants from air pollution include particulate matter (PM10), fine particulate matter (PM2.5), and ultrafine particles (UFP). Both short- and long-term exposure could result in various degrees of respiratory health outcomes among exposed persons, which rely on the individuals' health status. Methods. In this paper, we highlight a review of the studies that have used biomarkers to understand the association between air particles exposure and the development of respiratory problems resulting from the damage in the respiratory system. Data from previous epidemiological studies relevant to the application of biomarkers in respiratory system damage reported from exposure to air particles are also summarized. Results. Based on these analyses, the findings agree with the hypothesis that biomarkers are relevant in linking harmful air particles concentrations to increased respiratory health effects. Biomarkers are used in epidemiological studies to provide an understanding of the mechanisms that follow airborne particles exposure in the airway. However, application of biomarkers in epidemiological studies of health effects caused by air particles in both environmental and occupational health is inchoate. Conclusion. Biomarkers unravel the complexity of the connection between exposure to air particles and respiratory health. PMID:25984536

Understanding the use of continuous oscillating positive airway pressure (bubble CPAP) to treat neonatal respiratory disease: an engineering approach.

PubMed

Manilal-Reddy, P I; Al-Jumaily, A M

2009-01-01

A continuous oscillatory positive airway pressure with pressure oscillations incidental to the mean airway pressure (bubble CPAP) is defined as a modified form of traditional continuous positive airway pressure (CPAP) delivery where pressure oscillations in addition to CPAP are administered to neonates with lung diseases. The mechanical effect of the pressure oscillations on lung performance is investigated by formulating mathematical models of a typical bubble CPAP device and a simple representation of a neonatal respiratory system. Preliminary results of the respiratory system's mechanical response suggest that bubble CPAP may improve lung performance by minimizing the respiratory system impedance and that the resonant frequency of the respiratory system may be a controlling factor. Additional steps in terms of clinical trials and a more complex respiratory system model are required to gain a deeper insight into the mechanical receptiveness of the respiratory system to pressure oscillations. However, the current results are promising in that they offer a deeper insight into the trends of variations that can be expected in future extended models as well as the model philosophies that need to be adopted to produce results that are compatible with experimental verification.

Development of therapeutic antibodies to G protein-coupled receptors and ion channels: Opportunities, challenges and their therapeutic potential in respiratory diseases.

PubMed

Douthwaite, Julie A; Finch, Donna K; Mustelin, Tomas; Wilkinson, Trevor C I

2017-01-01

The development of recombinant antibody therapeutics continues to be a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Therapeutic drug targets such as soluble cytokines, growth factors and single transmembrane spanning receptors have been successfully targeted by recombinant monoclonal antibodies and the development of new product candidates continues. Despite this growth, however, certain classes of important disease targets have remained intractable to therapeutic antibodies due to the complexity of the target molecules. These complex target molecules include G protein-coupled receptors and ion channels which represent a large target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these important regulators of cell function. Given this opportunity, a significant effort has been applied to address the challenges of targeting these complex molecules and a number of targets are linked to the pathophysiology of respiratory diseases. In this review, we provide a summary of the importance of GPCRs and ion channels involved in respiratory disease and discuss advantages offered by antibodies as therapeutics at these targets. We highlight some recent GPCRs and ion channels linked to respiratory disease mechanisms and describe in detail recent progress made in the strategies for discovery of functional antibodies against challenging membrane protein targets such as GPCRs and ion channels. Copyright © 2016 Elsevier Inc. All rights reserved.

Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease

PubMed Central

Lax, Nichola Z.; Grady, John; Laude, Alex; Chan, Felix; Hepplewhite, Philippa D.; Gorman, Grainne; Whittaker, Roger G.; Ng, Yi; Cunningham, Mark O.

2015-01-01

Aims Mitochondrial disorders are among the most frequently inherited cause of neurological disease and arise due to mutations in mitochondrial or nuclear DNA. Currently, we do not understand the specific involvement of certain brain regions or selective neuronal vulnerability in mitochondrial disease. Recent studies suggest γ‐aminobutyric acid (GABA)‐ergic interneurones are particularly susceptible to respiratory chain dysfunction. In this neuropathological study, we assess the impact of mitochondrial DNA defects on inhibitory interneurones in patients with mitochondrial disease. Methods Histochemical, immunohistochemical and immunofluorescent assays were performed on post‐mortem brain tissue from 10 patients and 10 age‐matched control individuals. We applied a quantitative immunofluorescent method to interrogate complex I and IV protein expression in mitochondria within GABAergic interneurone populations in the frontal, temporal and occipital cortices. We also evaluated the density of inhibitory interneurones in serial sections to determine if cell loss was occurring. Results We observed significant, global reductions in complex I expression within GABAergic interneurones in frontal, temporal and occipital cortices in the majority of patients. While complex IV expression is more variable, there is reduced expression in patients harbouring m.8344A>G point mutations and POLG mutations. In addition to the severe respiratory chain deficiencies observed in remaining interneurones, quantification of GABAergic cell density showed a dramatic reduction in cell density suggesting interneurone loss. Conclusions We propose that the combined loss of interneurones and severe respiratory deficiency in remaining interneurones contributes to impaired neuronal network oscillations and could underlie development of neurological deficits, such as cognitive impairment and epilepsy, in mitochondrial disease. PMID:25786813

Cardiac metabolic pathways affected in the mouse model of barth syndrome.

PubMed

Huang, Yan; Powers, Corey; Madala, Satish K; Greis, Kenneth D; Haffey, Wendy D; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W; Khuchua, Zaza

2015-01-01

Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.

Hypoxic Episodes in Bronchopulmonary Dysplasia

PubMed Central

Martin, Richard J.; Di Fiore, Juliann M.; Walsh, Michele C.

2015-01-01

Hypoxic episodes are troublesome components of bronchopulmonary dysplasia in preterm infants. Immature respiratory control appears to be the major contributor, typically superimposed upon abnormal respiratory function. As a result, relatively short respiratory pauses may precipitate desaturation and accompanying bradycardia. As this population is predisposed to pulmonary hypertension, it is likely that pulmonary vasoconstriction may also play a role in hypoxic episodes. The natural history of intermittent hypoxic episodes has been well characterized in the preterm population at risk for BPD. However, the consequences of these episodes are less clear. Proposed associations of intermittent hypoxia include retinopathy of prematurity, sleep disordered breathing, and neurodevelopmental delay. Future study should address whether these associations are causal relationships. PMID:26593081

Reactive Oxygen Species Production by Forward and Reverse Electron Fluxes in the Mitochondrial Respiratory Chain

PubMed Central

Selivanov, Vitaly A.; Votyakova, Tatyana V.; Pivtoraiko, Violetta N.; Zeak, Jennifer; Sukhomlin, Tatiana; Trucco, Massimo; Roca, Josep; Cascante, Marta

2011-01-01

Reactive oxygen species (ROS) produced in the mitochondrial respiratory chain (RC) are primary signals that modulate cellular adaptation to environment, and are also destructive factors that damage cells under the conditions of hypoxia/reoxygenation relevant for various systemic diseases or transplantation. The important role of ROS in cell survival requires detailed investigation of mechanism and determinants of ROS production. To perform such an investigation we extended our rule-based model of complex III in order to account for electron transport in the whole RC coupled to proton translocation, transmembrane electrochemical potential generation, TCA cycle reactions, and substrate transport to mitochondria. It fits respiratory electron fluxes measured in rat brain mitochondria fueled by succinate or pyruvate and malate, and the dynamics of NAD+ reduction by reverse electron transport from succinate through complex I. The fitting of measured characteristics gave an insight into the mechanism of underlying processes governing the formation of free radicals that can transfer an unpaired electron to oxygen-producing superoxide and thus can initiate the generation of ROS. Our analysis revealed an association of ROS production with levels of specific radicals of individual electron transporters and their combinations in species of complexes I and III. It was found that the phenomenon of bistability, revealed previously as a property of complex III, remains valid for the whole RC. The conditions for switching to a state with a high content of free radicals in complex III were predicted based on theoretical analysis and were confirmed experimentally. These findings provide a new insight into the mechanisms of ROS production in RC. PMID:21483483

Characterization of an ntrX mutant of Neisseria gonorrhoeae reveals a response regulator that controls expression of respiratory enzymes in oxidase-positive proteobacteria.

PubMed

Atack, John M; Srikhanta, Yogitha N; Djoko, Karrera Y; Welch, Jessica P; Hasri, Norain H M; Steichen, Christopher T; Vanden Hoven, Rachel N; Grimmond, Sean M; Othman, Dk Seti Maimonah Pg; Kappler, Ulrike; Apicella, Michael A; Jennings, Michael P; Edwards, Jennifer L; McEwan, Alastair G

2013-06-01

NtrYX is a sensor-histidine kinase/response regulator two-component system that has had limited characterization in a small number of Alphaproteobacteria. Phylogenetic analysis of the response regulator NtrX showed that this two-component system is extensively distributed across the bacterial domain, and it is present in a variety of Betaproteobacteria, including the human pathogen Neisseria gonorrhoeae. Microarray analysis revealed that the expression of several components of the respiratory chain was reduced in an N. gonorrhoeae ntrX mutant compared to that in the isogenic wild-type (WT) strain 1291. These included the cytochrome c oxidase subunit (ccoP), nitrite reductase (aniA), and nitric oxide reductase (norB). Enzyme activity assays showed decreased cytochrome oxidase and nitrite reductase activities in the ntrX mutant, consistent with microarray data. N. gonorrhoeae ntrX mutants had reduced capacity to survive inside primary cervical cells compared to the wild type, and although they retained the ability to form a biofilm, they exhibited reduced survival within the biofilm compared to wild-type cells, as indicated by LIVE/DEAD staining. Analyses of an ntrX mutant in a representative alphaproteobacterium, Rhodobacter capsulatus, showed that cytochrome oxidase activity was also reduced compared to that in the wild-type strain SB1003. Taken together, these data provide evidence that the NtrYX two-component system may be a key regulator in the expression of respiratory enzymes and, in particular, cytochrome c oxidase, across a wide range of proteobacteria, including a variety of bacterial pathogens.

Respiratory complex I: 'steam engine' of the cell?

PubMed

Efremov, Rouslan G; Sazanov, Leonid A

2011-08-01

Complex I is the first enzyme of the respiratory chain and plays a central role in cellular energy production. It has been implicated in many human neurodegenerative diseases, as well as in ageing. One of the biggest membrane protein complexes, it is an L-shaped assembly consisting of hydrophilic and membrane domains. Previously, we have determined structures of the hydrophilic domain in several redox states. Last year was marked by fascinating breakthroughs in the understanding of the complete structure. We described the architecture of the membrane domain and of the entire bacterial complex I. X-ray analysis of the larger mitochondrial enzyme has also been published. The core subunits of the bacterial and mitochondrial enzymes have remarkably similar structures. The proposed mechanism of coupling between electron transfer and proton translocation involves long-range conformational changes, coordinated in part by a long α-helix, akin to the coupling rod of a steam engine. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

Route complexity and simulated physical ageing negatively influence wayfinding.

PubMed

Zijlstra, Emma; Hagedoorn, Mariët; Krijnen, Wim P; van der Schans, Cees P; Mobach, Mark P

2016-09-01

The aim of this age-simulation field experiment was to assess the influence of route complexity and physical ageing on wayfinding. Seventy-five people (aged 18-28) performed a total of 108 wayfinding tasks (i.e., 42 participants performed two wayfinding tasks and 33 performed one wayfinding task), of which 59 tasks were performed wearing gerontologic ageing suits. Outcome variables were wayfinding performance (i.e., efficiency and walking speed) and physiological outcomes (i.e., heart and respiratory rates). Analysis of covariance showed that persons on more complex routes (i.e., more floor and building changes) walked less efficiently than persons on less complex routes. In addition, simulated elderly participants perform worse in wayfinding than young participants in terms of speed (p < 0.001). Moreover, a linear mixed model showed that simulated elderly persons had higher heart rates and respiratory rates compared to young people during a wayfinding task, suggesting that simulated elderly consumed more energy during this task. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice

PubMed Central

Tupal, Srinivasan; Huang, Wei-Hsiang; Picardo, Maria Cristina D; Ling, Guang-Yi; Del Negro, Christopher A; Zoghbi, Huda Y; Gray, Paul A

2014-01-01

All motor behaviors require precise temporal coordination of different muscle groups. Breathing, for example, involves the sequential activation of numerous muscles hypothesized to be driven by a primary respiratory oscillator, the preBötzinger Complex, and at least one other as-yet unidentified rhythmogenic population. We tested the roles of Atoh1-, Phox2b-, and Dbx1-derived neurons (three groups that have known roles in respiration) in the generation and coordination of respiratory output. We found that Dbx1-derived neurons are necessary for all respiratory behaviors, whereas independent but coupled respiratory rhythms persist from at least three different motor pools after eliminating or silencing Phox2b- or Atoh1-expressing hindbrain neurons. Without Atoh1 neurons, however, the motor pools become temporally disorganized and coupling between independent respiratory oscillators decreases. We propose Atoh1 neurons tune the sequential activation of independent oscillators essential for the fine control of different muscles during breathing. DOI: http://dx.doi.org/10.7554/eLife.02265.001 PMID:24842997

Structural Basis of Resistance to Anti-Cytochrome bc1 Complex Inhibitors: Implication for Drug Improvement

PubMed Central

Esser, Lothar; Yu, Chang-An; Xia, Di

2016-01-01

The emergence of drug resistance has devastating economic and social consequences, a testimonial of which is the rise and fall of inhibitors against the respiratory component cytochrome bc1 complex, a time tested and highly effective target for disease control. Unfortunately, the mechanism of resistance is a multivariate problem, including primarily mutations in the gene of the cytochrome b subunit but also activation of alternative pathways of ubiquinol oxidation and pharmacokinetic effects. There is a considerable interest in designing new bc1 inhibitors with novel modes of binding and lower propensity to induce the development of resistance. The accumulation of crystallographic data of bc1 complexes with and without inhibitors bound provides the structural basis for rational drug design. In particular, the cytochrome b subunit offers two distinct active sites that can be targeted for inhibition - the quinol oxidation site and the quinone reduction site. This review brings together available structural information of inhibited bc1 by various quinol oxidation- and reduction-site inhibitors, the inhibitor binding modes, conformational changes upon inhibitor binding of side chains in the active site and large scale domain movements of the iron-sulfur protein subunit. Structural data analysis provides a clear understanding of where and why existing inhibitors fail and points towards promising alternatives. PMID:23688079

Involvement of an Alternative Oxidase in Oxidative Stress and Mycelium-to-Yeast Differentiation in Paracoccidioides brasiliensis ▿ †

PubMed Central

Martins, Vicente P.; Dinamarco, Taisa M.; Soriani, Frederico M.; Tudella, Valéria G.; Oliveira, Sergio C.; Goldman, Gustavo H.; Curti, Carlos; Uyemura, Sérgio A.

2011-01-01

Paracoccidioides brasiliensis is a thermodimorphic human pathogenic fungus that causes paracoccidioidomycosis (PCM), which is the most prevalent systemic mycosis in Latin America. Differentiation from the mycelial to the yeast form (M-to-Y) is an essential step for the establishment of PCM. We evaluated the involvement of mitochondria and intracellular oxidative stress in M-to-Y differentiation. M-to-Y transition was delayed by the inhibition of mitochondrial complexes III and IV or alternative oxidase (AOX) and was blocked by the association of AOX with complex III or IV inhibitors. The expression of P. brasiliensis aox (Pbaox) was developmentally regulated through M-to-Y differentiation, wherein the highest levels were achieved in the first 24 h and during the yeast exponential growth phase; Pbaox was upregulated by oxidative stress. Pbaox was cloned, and its heterologous expression conferred cyanide-resistant respiration in Saccharomyces cerevisiae and Escherichia coli and reduced oxidative stress in S. cerevisiae cells. These results reinforce the role of PbAOX in intracellular redox balancing and demonstrate its involvement, as well as that of other components of the mitochondrial respiratory chain complexes, in the early stages of the M-to-Y differentiation of P. brasiliensis. PMID:21183691

The CoQH2/CoQ Ratio Serves as a Sensor of Respiratory Chain Efficiency.

PubMed

Guarás, Adela; Perales-Clemente, Ester; Calvo, Enrique; Acín-Pérez, Rebeca; Loureiro-Lopez, Marta; Pujol, Claire; Martínez-Carrascoso, Isabel; Nuñez, Estefanía; García-Marqués, Fernando; Rodríguez-Hernández, María Angeles; Cortés, Ana; Diaz, Francisca; Pérez-Martos, Acisclo; Moraes, Carlos T; Fernández-Silva, Patricio; Trifunovic, Aleksandra; Navas, Plácido; Vazquez, Jesús; Enríquez, Jose A

2016-04-05

Electrons feed into the mitochondrial electron transport chain (mETC) from NAD- or FAD-dependent enzymes. A shift from glucose to fatty acids increases electron flux through FAD, which can saturate the oxidation capacity of the dedicated coenzyme Q (CoQ) pool and result in the generation of reactive oxygen species. To prevent this, the mETC superstructure can be reconfigured through the degradation of respiratory complex I, liberating associated complex III to increase electron flux via FAD at the expense of NAD. Here, we demonstrate that this adaptation is driven by the ratio of reduced to oxidized CoQ. Saturation of CoQ oxidation capacity induces reverse electron transport from reduced CoQ to complex I, and the resulting local generation of superoxide oxidizes specific complex I proteins, triggering their degradation and the disintegration of the complex. Thus, CoQ redox status acts as a metabolic sensor that fine-tunes mETC configuration in order to match the prevailing substrate profile. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Coevolution study of mitochondria respiratory chain proteins: toward the understanding of protein--protein interaction.

PubMed

Yang, Ming; Ge, Yan; Wu, Jiayan; Xiao, Jingfa; Yu, Jun

2011-05-20

Coevolution can be seen as the interdependency between evolutionary histories. In the context of protein evolution, functional correlation proteins are ever-present coordinated evolutionary characters without disruption of organismal integrity. As to complex system, there are two forms of protein--protein interactions in vivo, which refer to inter-complex interaction and intra-complex interaction. In this paper, we studied the difference of coevolution characters between inter-complex interaction and intra-complex interaction using "Mirror tree" method on the respiratory chain (RC) proteins. We divided the correlation coefficients of every pairwise RC proteins into two groups corresponding to the binary protein--protein interaction in intra-complex and the binary protein--protein interaction in inter-complex, respectively. A dramatical discrepancy is detected between the coevolution characters of the two sets of protein interactions (Wilcoxon test, p-value = 4.4 × 10(-6)). Our finding reveals some critical information on coevolutionary study and assists the mechanical investigation of protein--protein interaction. Furthermore, the results also provide some unique clue for supramolecular organization of protein complexes in the mitochondrial inner membrane. More detailed binding sites map and genome information of nuclear encoded RC proteins will be extraordinary valuable for the further mitochondria dynamics study. Copyright © 2011. Published by Elsevier Ltd.

RNA-binding proteins regulate cell respiration and coenzyme Q biosynthesis by post-transcriptional regulation of COQ7.

PubMed

Cascajo, María V; Abdelmohsen, Kotb; Noh, Ji Heon; Fernández-Ayala, Daniel J M; Willers, Imke M; Brea, Gloria; López-Lluch, Guillermo; Valenzuela-Villatoro, Marina; Cuezva, José M; Gorospe, Myriam; Siendones, Emilio; Navas, Plácido

2016-07-02

Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain carrying electrons from complexes I and II to complex III and it is an intrinsic component of the respirasome. CoQ concentration is highly regulated in cells in order to adapt the metabolism of the cell to challenges of nutrient availability and stress stimuli. At least 10 proteins have been shown to be required for CoQ biosynthesis in a multi-peptide complex and COQ7 is a central regulatory factor of this pathway. We found that the first 765 bp of the 3'-untranslated region (UTR) of COQ7 mRNA contains cis-acting elements of interaction with RNA-binding proteins (RBPs) HuR and hnRNP C1/C2. Binding of hnRNP C1/C2 to COQ7 mRNA was found to require the presence of HuR, and hnRNP C1/C2 silencing appeared to stabilize COQ7 mRNA modestly. By contrast, lowering HuR levels by silencing or depriving cells of serum destabilized and reduced the half-life of COQ7 mRNA, thereby reducing COQ7 protein and CoQ biosynthesis rate. Accordingly, HuR knockdown decreased oxygen consumption rate and mitochondrial production of ATP, and increased lactate levels. Taken together, our results indicate that a reduction in COQ7 mRNA levels by HuR depletion causes mitochondrial dysfunction and a switch toward an enhanced aerobic glycolysis, the characteristic phenotype exhibited by primary deficiency of CoQ10. Thus HuR contributes to efficient oxidative phosphorylation by regulating of CoQ10 biosynthesis.

Breathing

MedlinePlus Videos and Cool Tools

... system. Other components of the respiratory system conduct air to the lungs, such as the trachea (windpipe) ... and decreases the pressure inside. As a result, air rushes in and fills the lungs. During expiration, ...

Mobility of diesel versus non-diesel coal miners: some evidence on the healthy worker effect.

PubMed Central

Ames, R G; Trent, B

1984-01-01

Workers who are particularly susceptible to the effects of their occupational exposure, from the perspective of the healthy worker effect, soon leave the workplace. The result of this mobility, called survival bias, is that cross sectional studies based on the survivors underestimate the true risk of occupational exposures. Two questions are addressed in this empirical study of the "survival bias" component of the "healthy worker" effect. Do miners with respiratory impairment or symptoms disproportionately leave jobs that have a potentially harmful respiratory exposure? And does the presence of an additional potentially harmful respiratory exposure, in this case diesel emissions, accelerate the rate of mobility for miners with respiratory impairment or symptoms? No confirmation was found for the survival effect in a study of 738 diesel and 420 non-diesel US underground coal miners. No additional increment in mobility was associated with exposure to both coal mine dust and diesel emissions. PMID:6722047

Supramolecular organization of cytochrome c oxidase- and alternative oxidase-dependent respiratory chains in the filamentous fungus Podospora anserina.

PubMed

Krause, Frank; Scheckhuber, Christian Q; Werner, Alexandra; Rexroth, Sascha; Reifschneider, Nicole H; Dencher, Norbert A; Osiewacz, Heinz D

2004-06-18

To elucidate the molecular basis of the link between respiration and longevity, we have studied the organization of the respiratory chain of a wild-type strain and of two long-lived mutants of the filamentous fungus Podospora anserina. This established aging model is able to respire by either the standard or the alternative pathway. In the latter pathway, electrons are directly transferred from ubiquinol to the alternative oxidase and thus bypass complexes III and IV. We show that the cytochrome c oxidase pathway is organized according to the mammalian "respirasome" model (Schägger, H., and Pfeiffer, K. (2000) EMBO J. 19, 1777-1783). In contrast, the alternative pathway is composed of distinct supercomplexes of complexes I and III (i.e. I(2) and I(2)III(2)), which have not been described so far. Enzymatic analysis reveals distinct functional properties of complexes I and III belonging to either cytochrome c oxidase- or alternative oxidase-dependent pathways. By a gentle colorless-native PAGE, almost all of the ATP synthases from mitochondria respiring by either pathway were preserved in the dimeric state. Our data are of significance for the understanding of both respiratory pathways as well as lifespan control and aging.

Designing To Learn about Complex Systems.

ERIC Educational Resources Information Center

Hmelo, Cindy E.; Holton, Douglas L.; Kolodner, Janet L.

2000-01-01

Indicates the presence of complex structural, behavioral, and functional relations to understanding. Reports on a design experiment in which 6th grade children learned about the human respiratory system by designing artificial lungs and building partial working models. Makes suggestions for successful learning from design activities. (Contains 44…

Enhanced Critical Care Air Transport Team Training for Mitigation of Task Saturation

DTIC Science & Technology

2013-03-01

specialized members (physician, critical care nurse , and respiratory therapist) trained to handle the complex, critical nature of patients in hemodynamic ...with complex medical conditions have been poorly studied. 3.0 BACKGROUND Teams are composed of three medical personnel (a physician, a nurse , and

Pulmonary adverse effects of welding fume in automobile assembly welders.

PubMed

Sharifian, Seyed Akbar; Loukzadeh, Ziba; Shojaoddiny-Ardekani, Ahmad; Aminian, Omid

2011-01-01

Welding is one of the key components of numerous manufacturing industries, which has potential physical and chemical health hazards. Many components of welding fumes can potentially affect the lung function. This study investigates the effects of welding fumes on lung function and respiratory symptoms among welders of an automobile manufacturing plant in Iran. This historical cohort study assesses 43 male welders and 129 office workers by a questionnaire to record demographic data, smoking habits, work history and respiratory symptoms as well as lung function status by spirometry. The average pulmonary function values of welders were lower relative to controls with dose-effect relationship between work duration and pulmonary function impairment. The prevalence of chronic bronchitis was higher in welders than controls. Our findings suggest that welders are at risk for pulmonary disease.

The Arabidopsis Elongator complex is required for nonhost resistance against the bacterial pathogens Xanthomonas citri subsp. citri and Pseudomonas syringae pv. phaseolicola NPS3121.

PubMed

An, Chuanfu; Wang, Chenggang; Mou, Zhonglin

2017-05-01

Although in recent years nonhost resistance has attracted considerable attention for its broad spectrum and durability, the genetic and mechanistic components of nonhost resistance have not been fully understood. We used molecular and histochemical approaches including quantitative PCR, chromatin immunoprecipitation, and 3,3'-diaminobenzidine and aniline blue staining. The evolutionarily conserved histone acetyltransferase complex Elongator was identified as a major component of nonhost resistance against Xanthomonas citri subsp. citri (Xcc) and Pseudomonas syringae pv. phaseolicola (Psp) NPS3121. Mutations in Elongator genes inhibit Xcc-, Psp NPS3121- and/or flg22-induced defense responses including defense gene expression, callose deposition, and reactive oxygen species (ROS) and salicylic acid (SA) accumulation. Mutations in Elongator also attenuate the ROS-SA amplification loop. We show that suppressed ROS and SA accumulation in Elongator mutants is correlated with reduced expression of the Arabidopsis respiratory burst oxidase homologue AtrbohD and the SA biosynthesis gene ISOCHORISMATE SYNTHASE1 (ICS1). Furthermore, we found that the Elongator subunit ELP2 is associated with the chromatin of AtrbohD and ICS1 and is required for maintaining basal histone H3 acetylation levels in these key defense genes. As both AtrbohD and ICS1 contribute to nonhost resistance against Xcc, our results reveal an epigenetic mechanism by which Elongator regulates nonhost resistance in Arabidopsis. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

In female rat heart mitochondria, oophorectomy results in loss of oxidative phosphorylation.

PubMed

Pavón, Natalia; Cabrera-Orefice, Alfredo; Gallardo-Pérez, Juan Carlos; Uribe-Alvarez, Cristina; Rivero-Segura, Nadia A; Vazquez-Martínez, Edgar Ricardo; Cerbón, Marco; Martínez-Abundis, Eduardo; Torres-Narvaez, Juan Carlos; Martínez-Memije, Raúl; Roldán-Gómez, Francisco-Javier; Uribe-Carvajal, Salvador

2017-02-01

Oophorectomy in adult rats affected cardiac mitochondrial function. Progression of mitochondrial alterations was assessed at one, two and three months after surgery: at one month, very slight changes were observed, which increased at two and three months. Gradual effects included decrease in the rates of oxygen consumption and in respiratory uncoupling in the presence of complex I substrates, as well as compromised Ca 2+ buffering ability. Malondialdehyde concentration increased, whereas the ROS-detoxifying enzyme Mn 2+ superoxide dismutase (MnSOD) and aconitase lost activity. In the mitochondrial respiratory chain, the concentration and activity of complex I and complex IV decreased. Among other mitochondrial enzymes and transporters, adenine nucleotide carrier and glutaminase decreased. 2-Oxoglutarate dehydrogenase and pyruvate dehydrogenase also decreased. Data strongly suggest that in the female rat heart, estrogen depletion leads to progressive, severe mitochondrial dysfunction. © 2017 Society for Endocrinology.

The ubiquitous PM component Zn2+ induces HO-1 expression through multiple targets in the Nrf2/Keap1 signaling pathway

EPA Science Inventory

Oxidant stress can play an important role in particulate matter (PM)–mediated toxicity in the respiratory tract. Zinc (Zn2+) is a ubiquitous component of ambient PM that induces adverse responses such as inflammatory and adaptive gene expression in human airway epithelial c...

The Role of the Microbiome in Exacerbations of Chronic Lung Diseases

PubMed Central

Dickson, Robert P.; Martinez, Fernando J.; Huffnagle, Gary B.

2014-01-01

Summary Culture-independent microbiological techniques have revealed a previously unappreciated complexity to the bacterial microbiome of the respiratory tract, forcing reconsideration of the interactions between host, bacteria and the pathogenesis of exacerbations of chronic lung disease. The composition of the lung microbiome is determined by microbial immigration, elimination, and the relative growth rates of its members; all of these change dramatically in chronic lung disease and further during exacerbations. Exacerbations lack key features of bacterial infections, including increased bacterial burden and decreased community diversity. We propose instead that exacerbations are occasions of respiratory dysbiosis: a disordered respiratory microbial ecosystem with negative effects on host biology. Respiratory dysbiosis provokes a dysregulated host immune response, which in turn alters microbial growth conditions in patient airways, further promoting dysbiosis and perpetuating a coupled cycle of inflammation and disordered microbiota. Differences in baseline respiratory microbiota may help explain the “frequent-exacerbator” phenotype observed across multiple disease states, and may provide novel targets for therapeutic intervention. PMID:25152271

Increasing Prevalence of Nontuberculous Mycobacteria in Respiratory Specimens from US-Affiliated Pacific Island Jurisdictions1

PubMed Central

Russell, Chad; Soll, Bruce; Chow, Dominic; Bamrah, Sapna; Brostrom, Richard; Kim, Wesley; Scott, Jerry; Bankowski, Matthew J.

2018-01-01

Nontuberculous mycobacteria (NTM) respiratory infections represent a growing public health problem in many countries. However, there are limited published epidemiologic studies for the Western Pacific region. We reviewed respiratory specimens submitted to Diagnostic Laboratory Services in Hawaii, USA, for culture of Mycobacterium tuberculosis during August 2007–December 2011 to determine the NTM isolation rate. We observed a statistically significant increase in the rate of specimens with NTM isolated in respiratory culture (adjusted rate ratio per year 1.65, 95% CI 1.54–1.77; p<0.01). In contrast, the number of patients with respiratory cultures positive for M. tuberculosis showed no increase (adjusted rate ratio per year 0.98, 95% CI 0.94–1.01; p = 0.19). A 6-month subset of NTM isolates was identified by using a nucleic acid probe or 16S rRNA sequencing. M. avium complex and M. fortuitum were the most common NTM identified. PMID:29460734

Fractal-Based Analysis of the Influence of Music on Human Respiration

NASA Astrophysics Data System (ADS)

Reza Namazi, H.

An important challenge in respiration related studies is to investigate the influence of external stimuli on human respiration. Auditory stimulus is an important type of stimuli that influences human respiration. However, no one discovered any trend, which relates the characteristics of the auditory stimuli to the characteristics of the respiratory signal. In this paper, we investigate the correlation between auditory stimuli and respiratory signal from fractal point of view. We found out that the fractal structure of respiratory signal is correlated with the fractal structure of the applied music. Based on the obtained results, the music with greater fractal dimension will result in respiratory signal with smaller fractal dimension. In order to verify this result, we benefit from approximate entropy. The results show the respiratory signal will have smaller approximate entropy by choosing the music with smaller approximate entropy. The method of analysis could be further investigated to analyze the variations of different physiological time series due to the various types of stimuli when the complexity is the main concern.

Respiratory Muscle Plasticity

PubMed Central

Gransee, Heather M.; Mantilla, Carlos B.; Sieck, Gary C.

2014-01-01

Muscle plasticity is defined as the ability of a given muscle to alter its structural and functional properties in accordance with the environmental conditions imposed on it. As such, respiratory muscle is in a constant state of remodeling, and the basis of muscle’s plasticity is its ability to change protein expression and resultant protein balance in response to varying environmental conditions. Here, we will describe the changes of respiratory muscle imposed by extrinsic changes in mechanical load, activity, and innervation. Although there is a large body of literature on the structural and functional plasticity of respiratory muscles, we are only beginning to understand the molecular-scale protein changes that contribute to protein balance. We will give an overview of key mechanisms regulating protein synthesis and protein degradation, as well as the complex interactions between them. We suggest future application of a systems biology approach that would develop a mathematical model of protein balance and greatly improve treatments in a variety of clinical settings related to maintaining both muscle mass and optimal contractile function of respiratory muscles. PMID:23798306

The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

PubMed Central

Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

2015-01-01

The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

MafB deficiency causes defective respiratory rhythmogenesis and fatal central apnea at birth.

PubMed

Blanchi, Bruno; Kelly, Louise M; Viemari, Jean-Charles; Lafon, Isabelle; Burnet, Henri; Bévengut, Michelle; Tillmanns, Silke; Daniel, Laurent; Graf, Thomas; Hilaire, Gerard; Sieweke, Michael H

2003-10-01

The genetic basis for the development of brainstem neurons that generate respiratory rhythm is unknown. Here we show that mice deficient for the transcription factor MafB die from central apnea at birth and are defective for respiratory rhythmogenesis in vitro. MafB is expressed in a subpopulation of neurons in the preBötzinger complex (preBötC), a putative principal site of rhythmogenesis. Brainstems from Mafb(-/-) mice are insensitive to preBötC electrolytic lesion or stimulation and modulation of rhythmogenesis by hypoxia or peptidergic input. Furthermore, in Mafb(-/-) mice the preBötC, but not major neuromodulatory groups, presents severe anatomical defects with loss of cellularity. Our results show an essential role of MafB in central respiratory control, possibly involving the specification of rhythmogenic preBötC neurons.

Respiratory chain complex I deficiency due to NDUFA12 mutations as a new cause of Leigh syndrome.

PubMed

Ostergaard, Elsebet; Rodenburg, Richard J; van den Brand, Mariël; Thomsen, Lise Lykke; Duno, Morten; Batbayli, Mustafa; Wibrand, Flemming; Nijtmans, Leo

2011-11-01

This study investigated a girl with Leigh syndrome born to first-cousin parents of Pakistani descent with an isolated respiratory chain complex I deficiency in muscle and fibroblasts. Her early development was delayed, and from age 2 years she started losing motor abilities. Cerebral MRI showed basal ganglia lesions typical of Leigh syndrome. A genome-wide search for homozygosity was performed with the Affymetrix GeneChip 50K Xba array. The analysis revealed several homozygous regions. Three candidate genes were identified, and in one of the genes, NDUFA12, a homozygous c.178C→T mutation leading to a premature stop codon (p.Arg60X) was found. Western blot analysis showed absence of NDUFA12 protein in patient fibroblasts and functional complementation by a baculovirus system showed restoration of complex I activity. NDUFA12 mutations are apparently not a frequent cause of complex I deficiency, since mutations were not found by screening altogether 122 complex I deficient patients in two different studies. NDUFA12 encodes an accessory subunit of complex I and is a paralogue of NDUFAF2. Despite the complete absence of NDUFA12 protein, a fully assembled and enzymatically active complex I could be found, albeit in reduced amounts. This suggests that NDUFA12 is required either at a late step in the assembly of complex I, or in the stability of complex I.

Mitochondrial Respiration in Insulin-Producing β-Cells: General Characteristics and Adaptive Effects of Hypoxia

PubMed Central

Ma, Zuheng; Scholz, Hanne; Björklund, Anneli; Grill, Valdemar

2015-01-01

Objective To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Methods and Design Insulin-producing INS-1 832/13 cells were exposed to 18 hours of hypoxia followed by 20–22 hours re-oxygenation. Mitochondrial respiration was measured by high-resolution respirometry in both intact and permeabilized cells, in the latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins of mitochondrial complexes (Western blotting), ATP and insulin secretion. Results Intact cells exhibited a high degree of intrinsic uncoupling, comprising about 50% of oxygen consumption in the basal respiratory state. Hypoxia followed by re-oxygenation increased maximal overall respiration. Exploratory experiments in peremabilized cells could not show induction of respiration by malate or pyruvate as reducing substrates, thus glutamate and succinate were used as mitochondrial substrates in SUIT protocols. Permeabilized cells displayed a high capacity for oxidative phosphorylation for both complex I- and II-linked substrates in relation to maximum capacity of electron transfer. Previous hypoxia decreased phosphorylation control of complex I-linked respiration, but not in complex II-linked respiration. Coupling control ratios showed increased coupling efficiency for both complex I- and II-linked substrates in hypoxia-exposed cells. Respiratory rates overall were increased. Also previous hypoxia increased proteins of mitochondrial complexes I and II (Western blotting) in INS-1 cells as well as in rat and human islets. Mitochondrial effects were accompanied by unchanged levels of ATP, increased basal and preserved glucose-induced insulin secretion. Conclusions Exposure of INS-1 832/13 cells to hypoxia, followed by a re-oxygenation period increases substrate-stimulated respiratory capacity and coupling efficiency. Such effects are accompanied by up-regulation of mitochondrial complexes also in pancreatic islets, highlighting adaptive capacities of possible importance in an islet transplantation setting. Results also indicate idiosyncrasies of β-cells that do not respire in response to a standard inclusion of malate in SUIT protocols. PMID:26401848

Mitochondrial Respiration in Insulin-Producing β-Cells: General Characteristics and Adaptive Effects of Hypoxia.

PubMed

Hals, Ingrid K; Bruerberg, Simon Gustafson; Ma, Zuheng; Scholz, Hanne; Björklund, Anneli; Grill, Valdemar

2015-01-01

To provide novel insights on mitochondrial respiration in β-cells and the adaptive effects of hypoxia. Insulin-producing INS-1 832/13 cells were exposed to 18 hours of hypoxia followed by 20-22 hours re-oxygenation. Mitochondrial respiration was measured by high-resolution respirometry in both intact and permeabilized cells, in the latter after establishing three functional substrate-uncoupler-inhibitor titration (SUIT) protocols. Concomitant measurements included proteins of mitochondrial complexes (Western blotting), ATP and insulin secretion. Intact cells exhibited a high degree of intrinsic uncoupling, comprising about 50% of oxygen consumption in the basal respiratory state. Hypoxia followed by re-oxygenation increased maximal overall respiration. Exploratory experiments in peremabilized cells could not show induction of respiration by malate or pyruvate as reducing substrates, thus glutamate and succinate were used as mitochondrial substrates in SUIT protocols. Permeabilized cells displayed a high capacity for oxidative phosphorylation for both complex I- and II-linked substrates in relation to maximum capacity of electron transfer. Previous hypoxia decreased phosphorylation control of complex I-linked respiration, but not in complex II-linked respiration. Coupling control ratios showed increased coupling efficiency for both complex I- and II-linked substrates in hypoxia-exposed cells. Respiratory rates overall were increased. Also previous hypoxia increased proteins of mitochondrial complexes I and II (Western blotting) in INS-1 cells as well as in rat and human islets. Mitochondrial effects were accompanied by unchanged levels of ATP, increased basal and preserved glucose-induced insulin secretion. Exposure of INS-1 832/13 cells to hypoxia, followed by a re-oxygenation period increases substrate-stimulated respiratory capacity and coupling efficiency. Such effects are accompanied by up-regulation of mitochondrial complexes also in pancreatic islets, highlighting adaptive capacities of possible importance in an islet transplantation setting. Results also indicate idiosyncrasies of β-cells that do not respire in response to a standard inclusion of malate in SUIT protocols.

Potential impact of fireworks on respiratory health

PubMed Central

Gouder, Caroline; Montefort, Stephen

2014-01-01

The world-wide use of fireworks with their consequent detrimental effect on the air quality is widely recognized with elevated ambient air levels of particulate matter and its several metallic components and gases identified in several studies carried out during such events. Exposed individuals may be at risk following inhalation of such produced pollutants. This review focuses on the impact of fireworks on air quality and the potential effect of fireworks on the respiratory system of healthy individuals as well as those suffering from underlying respiratory diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). This applies not only to spectators including children but also to pyrotechnicians themselves. An extensive Medline search revealed that a strong evidence of the impact of fireworks on respiratory health is lacking in susceptible as well as healthy individuals with no formal studies on COPD or asthma, other than a few case reports in the latter. The implementation of global strategies to control the use of fireworks and hence improve air quality could possibly reduce their likely detrimental effect on human respiratory health in exposed individuals, but clearly a more targeted research is needed. PMID:25378846

Electron transport chains in organohalide-respiring bacteria and bioremediation implications.

PubMed

Wang, Shanquan; Qiu, Lan; Liu, Xiaowei; Xu, Guofang; Siegert, Michael; Lu, Qihong; Juneau, Philippe; Yu, Ling; Liang, Dawei; He, Zhili; Qiu, Rongliang

In situ remediation employing organohalide-respiring bacteria represents a promising solution for cleanup of persistent organohalide pollutants. The organohalide-respiring bacteria conserve energy by utilizing H 2 or organic compounds as electron donors and organohalides as electron acceptors. Reductive dehalogenase (RDase), a terminal reductase of the electron transport chain in organohalide-respiring bacteria, is the key enzyme that catalyzes halogen removal. Accumulating experimental evidence thus far suggests that there are distinct models for respiratory electron transfer in organohalide-respirers of different lineages, e.g., Dehalococcoides, Dehalobacter, Desulfitobacterium and Sulfurospirillum. In this review, to connect the knowledge in organohalide-respiratory electron transport chains to bioremediation applications, we first comprehensively review molecular components and their organization, together with energetics of the organohalide-respiratory electron transport chains, as well as recent elucidation of intramolecular electron shuttling and halogen elimination mechanisms of RDases. We then highlight the implications of organohalide-respiratory electron transport chains in stimulated bioremediation. In addition, major challenges and further developments toward understanding the organohalide-respiratory electron transport chains and their bioremediation applications are identified and discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Structural basis of respiratory syncytial virus neutralization by motavizumab

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

McLellan, Jason S.; Chen, Man; Kim, Albert

2010-04-13

Motavizumab is {approx}tenfold more potent than its predecessor, palivizumab (Synagis), the FDA-approved monoclonal antibody used to prevent respiratory syncytial virus (RSV) infection. The structure of motavizumab in complex with a 24-residue peptide corresponding to its epitope on the RSV fusion (F) glycoprotein reveals the structural basis for this greater potency. Modeling suggests that motavizumab recognizes a different quaternary configuration of the F glycoprotein than that observed in a homologous structure.

Bachelor of science degree education programs: organization, structure, and curriculum.

PubMed

Douce, F Herbert

2005-09-01

Therapists with bachelor's degrees in respiratory therapy have become the new advanced clinicians of the twenty-first century. Although the opportunity has increased in recent years, earning a baccalaureate degree in respiratory therapy remains a limited option. The "2-year preprofessional plus 2-year respiratory therapy" is the most popular curriculum design, but several other notable designs also fulfill the definition of a bachelor's degree in respiratory therapy. Two landmark documents issued in 2003 make strong arguments for expanding opportunities for baccalaureate education in respiratory therapy. Recognizing the "need to increase the number of respiratory therapists with advanced levels of training and education to meet the demands of providing services requiring complex cognitive abilities and patient management skills," the American Association for Respiratory Therapy has strongly encouraged the continuing development of baccalaureate education. Strategies for expanding baccalaureate opportunities include increasing the number and capacities of traditional programs, creating more articulation and bridge agreements between community and junior colleges with 4-year colleges and universities, and offering baccalaureate respiratory therapy through distance education. For the profession of respiratory therapy to require a baccalaureate at entry level, expansion of baccalaureate education will be necessary, and educators, managers, practitioners, and professional leaders will need to pursue all viable strategies. As an interim phase in the evolution of the profession, Becker suggests a strategy of"reprofessionalism" aimed at assisting therapists currently in the workforce to complete their degrees. Through a combination of strategies, a bachelor's degree in respiratory therapy will inevitably become the standard for clinicians in the decades to come.

Connecting students to institutions: the relationship between program resources and student retention in respiratory care education programs.

PubMed

Ari, Arzu

2009-09-01

Respiratory care education programs are being held accountable for student retention. Increasing student retention is necessary for the respiratory therapy profession, which suffers from a shortage of qualified therapists needed to meet the increased demand. The present study investigated the relationship between student retention rate and program resources, in order to understand which and to what extent the different components of program resources predict student retention rate. The target population of this study was baccalaureate of science degree respiratory care education programs. After utilizing a survey research method, Pearson correlations and multiple regression analysis were used for data analysis. With a 63% response rate (n = 36), this study found a statistically significant relationship between program resources and student retention rate. Financial and personnel resources had a statistically significant positive relationship with student retention. The mean financial resources per student was responsible for 33% of the variance in student retention, while the mean personnel resources per student accounted for 12% of the variance in student retention. Program financial resources available to students was the single best predictor of program performance on student retention. Respiratory care education programs spending more money per student and utilizing more personnel in the program have higher mean performance in student retention. Therefore, respiratory care education programs must devote sufficient resources to retaining students so that they can produce more respiratory therapists and thereby make the respiratory therapy profession stronger.

Roles of Neuroglobin Binding to Mitochondrial Complex III Subunit Cytochrome c1 in Oxygen-Glucose Deprivation-Induced Neurotoxicity in Primary Neurons.

PubMed

Yu, Zhanyang; Zhang, Yu; Liu, Ning; Yuan, Jing; Lin, Li; Zhuge, Qichuan; Xiao, Jian; Wang, Xiaoying

2016-07-01

Neuroglobin (Ngb) is a tissue globin specifically expressed in brain neurons. Recent studies by our laboratory and others have demonstrated that Ngb is protective against stroke and related neurological disorders, but the mechanisms remain poorly understood. We previously identified cytochrome c1 (Cyc1) as an Ngb-interacting molecule by yeast two-hybrid screening. Cyc1 is a subunit of mitochondria complex III, which is a component of mitochondrial respiratory chain and a major source of reactive oxygen species (ROS) production under both physiological and pathological conditions. In this study, we for the first time defined Ngb-Cyc1 binding, and investigated its roles in oxygen-glucose deprivation (OGD)/reoxygenation-induced neurotoxicity and ROS production in primary neurons. Immunocytochemistry and co-immunoprecipitation validated Ngb-Cyc1 binding, which was significantly increased by OGD and Ngb overexpression. We found 4 h OGD with/without 4 h reoxygenation significantly increased complex III activity, but this activity elevation was significantly attenuated in three groups of neurons: Ngb overexpression, specific complex III inhibitor stigmatellin, or stigmatellin plus Ngb overexpression, whereas there was no significant differences between these three groups, suggesting Ngb-Cyc1 binding may function in suppressing OGD-mediated complex III activity elevation. Importantly, these three groups of neurons also showed significant decreases in OGD-induced superoxide anion generation and neurotoxicity. These results suggest that Ngb can bind to mitochondrial complex III subunit Cyc1, leading to suppression of OGD-mediated complex III activity and subsequent ROS production elevation, and eventually reduction of OGD-induced neurotoxicity. This molecular signaling cascade may be at least part of the mechanisms of Ngb neuroprotection against OGD-induced neurotoxicity.

Respiratory comfort and breathing pattern during volume proportional assist ventilation and pressure support ventilation: a study on volunteers with artificially reduced compliance.

PubMed

Mols, G; von Ungern-Sternberg, B; Rohr, E; Haberthür, C; Geiger, K; Guttmann, J

2000-06-01

To assess respiratory comfort and associated breathing pattern during volume assist (VA) as a component of proportional assist ventilation and during pressure support ventilation (PSV). Prospective, double-blind, interventional study. Laboratory. A total of 15 healthy volunteers (11 females, 4 males) aged 21-31 yrs. Decreased respiratory system compliance was simulated by banding of the thorax and abdomen. Volunteers breathed via a mouthpiece with VA and PSV each applied at two levels (VA, 8 cm H2O/L and 12 cm H2O/L; PSV, 10 cm H2O and 15 cm H2O) using a positive end-expiratory pressure of 5 cm H2O throughout. The study was subdivided into two parts. In Part 1, volunteers breathed three times with each of the four settings for 2 mins in random order. In Part 2, the first breath effects of multiple, randomly applied mode, and level shifts were studied. In Part 1, the volunteers were asked to estimate respiratory comfort in comparison with normal breathing using a visual analog scale. In Part 2, they were asked to estimate the change of respiratory comfort as increased, decreased, or unchanged immediately after a mode shift. Concomitantly, the respiratory pattern (change) was characterized with continuously measured tidal volume, respiratory rate, pressure, and gas flow. Respiratory comfort during VA was higher than during PSV. The higher support level was less important during VA but had a major negative influence on comfort during PSV. Both modes differed with respect to the associated breathing pattern. Variability of breathing was higher during VA than during PSV (Part 1). Changes in respiratory variables were associated with changes in respiratory comfort (Part 2). For volunteers breathing with artificially reduced respiratory system compliance, respiratory comfort is higher with VA than with PSV. This is probably caused by a better adaptation of the ventilatory support to the volunteer's need with VA.

Quantifying functional mobility progress for chronic disease management.

PubMed

Boyle, Justin; Karunanithi, Mohan; Wark, Tim; Chan, Wilbur; Colavitti, Christine

2006-01-01

A method for quantifying improvements in functional mobility is presented based on patient-worn accelerometer devices. For patients with cardiovascular, respiratory, or other chronic disease, increasing the amount of functional mobility is a large component of rehabilitation programs. We have conducted an observational trial on the use of accelerometers for quantifying mobility improvements in a small group of chronic disease patients (n=15, 48 - 86 yrs). Cognitive impairments precluded complex instrumentation of patients, and movement data was obtained from a single 2-axis accelerometer device worn at the hip. In our trial, movement data collected from accelerometer devices was classified into Lying vs Sitting/Standing vs Walking/Activity movements. This classification enabled the amount of walking to be quantified and graphically presented to clinicians and carers for feedback on exercise efficacy. Presenting long term trends in this data to patients also provides valuable feedback for self managed care and assisting with compliance.

Bacterial inactivation of the anticancer drug doxorubicin.

PubMed

Westman, Erin L; Canova, Marc J; Radhi, Inas J; Koteva, Kalinka; Kireeva, Inga; Waglechner, Nicholas; Wright, Gerard D

2012-10-26

Microbes are exposed to compounds produced by members of their ecological niche, including molecules with antibiotic or antineoplastic activities. As a result, even bacteria that do not produce such compounds can harbor the genetic machinery to inactivate or degrade these molecules. Here, we investigated environmental actinomycetes for their ability to inactivate doxorubicin, an aminoglycosylated anthracycline anticancer drug. One strain, Streptomyces WAC04685, inactivates doxorubicin via a deglycosylation mechanism. Activity-based purification of the enzymes responsible for drug inactivation identified the NADH dehydrogenase component of respiratory electron transport complex I, which was confirmed by gene inactivation studies. A mechanism where reduction of the quinone ring of the anthracycline by NADH dehydrogenase leads to deglycosylation is proposed. This work adds anticancer drug inactivation to the enzymatic inactivation portfolio of actinomycetes and offers possibilities for novel applications in drug detoxification. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Automated RNA amplification for the rapid identification of Mycobacterium tuberculosis complex in respiratory specimens].

PubMed

Drouillon, V; Houriez, F; Buze, M; Lagrange, P; Herrmann, J-L

2006-01-01

Rapid and sensitive detection of Mycobacterium tuberculosis complex (MTB) directly on clinical respiratory specimens is essential for a correct management of patients suspected of tuberculosis. For this purpose PCR-based kits are available to detect MTB in respiratory specimen but most of them need at least 4 hours to be completed. New methods, based on TRC method (TRC: Transcription Reverse transcription Concerted--TRCRapid M. Tuberculosis--Tosoh Bioscience, Tokyo, Japon) and dedicated monitor have been developed. A new kit (TRC Rapid M. tuberculosis and Real-time monitor TRCRapid-160, Tosoh Corporation, Japan) enabling one step amplification and real-time detection of MTB 16S rRNA by a combination of intercalative dye oxazole yellow-linked DNA probe and isothermal RNA amplification directly on respiratory specimens has been tested in our laboratory. 319 respiratory specimens were tested in this preliminary study and results were compared to smear and culture. Fourteen had a positive culture for MTB. Among theses samples, smear was positive in 11 cases (78.6%) and TRC process was positive in 8 cases (57.1%). Overall sensitivity of TRC compared to smear positive samples is 73%. Theses first results demonstrated that a rapid identification of MTB was possible (less than 2 processing hours for 14 specimens and about 1 hour for 1 specimen) in most cases of smear positive samples using ready to use reagents for real time detection of MTB rRNA in clinical samples. New pretreatment and extraction reagents kits to increase the stability of the sputum RNA and the extraction efficiency are now tested in our laboratory.

The effect of low-frequency oscillations on cardio-respiratory synchronization. Observations during rest and exercise

NASA Astrophysics Data System (ADS)

Kenwright, D. A.; Bahraminasab, A.; Stefanovska, A.; McClintock, P. V. E.

2008-10-01

We show that the transitions which occur between close orders of synchronization in the cardiorespiratory system are mainly due to modulation of the cardiac and respiratory processes by low-frequency components. The experimental evidence is derived from recordings on healthy subjects at rest and during exercise. Exercise acts as a perturbation of the system that alters the mean cardiac and respiratory frequencies and changes the amount of their modulation by low-frequency oscillations. The conclusion is supported by numerical evidence based on a model of phase-coupled oscillators, with white noise and lowfrequency noise. Both the experimental and numerical approaches confirm that low-frequency oscillations play a significant role in the transitional behavior between close orders of synchronization.

Robust lung identification in MSCT via controlled flooding and shape constraints: dealing with anatomical and pathological specificity

NASA Astrophysics Data System (ADS)

Fetita, Catalin; Tarando, Sebastian; Brillet, Pierre-Yves; Grenier, Philippe A.

2016-03-01

Correct segmentation and labeling of lungs in thorax MSCT is a requirement in pulmonary/respiratory disease analysis as a basis for further processing or direct quantitative measures: lung texture classification, respiratory functional simulations, intrapulmonary vascular remodeling evaluation, detection of pleural effusion or subpleural opacities, are only few clinical applications related to this requirement. Whereas lung segmentation appears trivial for normal anatomo-pathological conditions, the presence of disease may complicate this task for fully-automated algorithms. The challenges come either from regional changes of lung texture opacity or from complex anatomic configurations (e.g., thin septum between lungs making difficult proper lung separation). They make difficult or even impossible the use of classic algorithms based on adaptive thresholding, 3-D connected component analysis and shape regularization. The objective of this work is to provide a robust segmentation approach of the pulmonary field, with individualized labeling of the lungs, able to overcome the mentioned limitations. The proposed approach relies on 3-D mathematical morphology and exploits the concept of controlled relief flooding (to identify contrasted lung areas) together with patient-specific shape properties for peripheral dense tissue detection. Tested on a database of 40 MSCT of pathological lungs, the proposed approach showed correct identification of lung areas with high sensitivity and specificity in locating peripheral dense opacities.

Dynamics of enhanced mitochondrial respiration in female compared with male rat cerebral arteries.

PubMed

Rutkai, Ibolya; Dutta, Somhrita; Katakam, Prasad V; Busija, David W

2015-11-01

Mitochondrial respiration has never been directly examined in intact cerebral arteries. We tested the hypothesis that mitochondrial energetics of large cerebral arteries ex vivo are sex dependent. The Seahorse XFe24 analyzer was used to examine mitochondrial respiration in isolated cerebral arteries from adult male and female Sprague-Dawley rats. We examined the role of nitric oxide (NO) on mitochondrial respiration under basal conditions, using N(ω)-nitro-l-arginine methyl ester, and following pharmacological challenge using diazoxide (DZ), and also determined levels of mitochondrial and nonmitochondrial proteins using Western blot, and vascular diameter responses to DZ. The components of mitochondrial respiration including basal respiration, ATP production, proton leak, maximal respiration, and spare respiratory capacity were elevated in females compared with males, but increased in both male and female arteries in the presence of the NOS inhibitor. Although acute DZ treatment had little effect on mitochondrial respiration of male arteries, it decreased the respiration in female arteries. Levels of mitochondrial proteins in Complexes I-V and the voltage-dependent anion channel protein were elevated in female compared with male cerebral arteries. The DZ-induced vasodilation was greater in females than in males. Our findings show that substantial sex differences in mitochondrial respiratory dynamics exist in large cerebral arteries and may provide the mechanistic basis for observations that the female cerebral vasculature is more adaptable after injury. Copyright © 2015 the American Physiological Society.

TLR-activated repression of Fe-S cluster biogenesis drives a metabolic shift and alters histone and tubulin acetylation.

PubMed

Tong, Wing-Hang; Maio, Nunziata; Zhang, De-Liang; Palmieri, Erika M; Ollivierre, Hayden; Ghosh, Manik C; McVicar, Daniel W; Rouault, Tracey A

2018-05-22

Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17. Previous studies have shown that the metabolic shift in Toll-like receptor (TLR)-activated myeloid cells involves rapid activation of glycolysis and subsequent mitochondrial respiratory failure due to nitric oxide (NO)-mediated damage to Fe-S proteins. Our studies indicated that TLR activation also actively suppresses many components of the Fe-S cluster biogenesis machinery, which exacerbates NO-mediated damage to Fe-S proteins by interfering with cluster recovery. These results reveal new regulatory pathways and novel roles of the Fe-S cluster biogenesis machinery in modifying the epigenome and acetylome and provide new insights into the etiology of Fe-S cluster biogenesis disorders.

Vapor, Dust and Smoke Exposure in relation to adult-onset asthma and chronic respiratory symptoms: The Singapore Chinese Health Study

PubMed Central

LeVan, Tricia D.; Koh, Woon-Puay; Lee, Hin-Peng; Koh, David; Yu, Mimi C.; London, Stephanie J.

2006-01-01

Occupational factors contribute to a significant fraction of respiratory disease and symptoms. We evaluated the role of occupational exposures on asthma, chronic bronchitis, and respiratory symptoms in a population-based cohort, the Singapore Chinese Health Study. History of occupations, occupational exposures, and respiratory conditions were collected by interviews with 52,325 Singaporeans born 1918–1953. Exposure to dusts, from cotton, wood, metal, mineral and/or asbestos, was associated with non-chronic cough and/or phlegm (OR = 1.19, 95% CI = 1.08, 1.30), chronic bronchitis (OR = 1.26, 95% CI = 1.01, 1.57) and adult-onset asthma (OR = 1.14, 95% CI = 1.00, 1.30). Cotton dust was the major component contributing to respiratory symptoms. Vapor exposure, from chemical solvents, dyes, cooling oils, paints, wood preservatives and/or pesticides, was associated with non-chronic cough or phlegm (OR = 1.14, 95% CI = 1.03, 1.27), chronic dry cough (OR = 1.55, 95% CI = 1.19, 2.01) and adult-onset asthma (OR = 1.34, 95% CI = 1.15, 1.56). Chemical solvents, cooling oils and pesticides were the major sources contributing to respiratory symptoms. These data support the role of occupational exposures in the etiology of respiratory illness in a population-based cohort in Singapore with a low prevalence of atopic illness. PMID:16707657

Activation of respiratory muscles during weaning from mechanical ventilation.

PubMed

Walterspacher, Stephan; Gückler, Julia; Pietsch, Fabian; Walker, David Johannes; Kabitz, Hans-Joachim; Dreher, Michael

2017-04-01

Respiratory muscle dysfunction is a key component of weaning failure. Balancing respiratory muscle loading and unloading by applying different ventilation modes along with spontaneous breathing episodes are established weaning strategies. However, the effects of body positioning on the respiratory muscles during weaning remains unclear. This study aimed at assessing respiratory drive by surface electromyography (EMG) of the diaphragm (EMG dia ) and parasternal muscles (EMG para ) in tracheotomized patients during prolonged weaning in 3 randomized body positions-supine, 30° semirecumbent, and 80° sitting-during mechanical ventilation and spontaneous breathing. Nine patients were included for analysis. Cardiorespiratory parameters (heart rate, blood pressure, arterial oxygen saturation, dyspnea) did not change under each condition (all P>.05). EMG para and EMG dia did not change under mechanical ventilation (both P>.05). EMG dia changed under spontaneous breathing from supine to sitting (0.45±0.26 vs 0.32±0.19; P=.012) and between semirecumbent to sitting (0.41±0.23 vs 0.32±0.19; P=.039), whereas EMG para did not change. This is the first study to show that body positioning influences respiratory drive to the diaphragm in tracheotomized patients with prolonged weaning from mechanical ventilation during unassisted breathing. Sitting position reduces respiratory drive compared with semirecumbent and supine positioning and might therefore be favored during spontaneous breathing trials. Copyright © 2016 Elsevier Inc. All rights reserved.

Expanding severe acute respiratory infection (SARI) surveillance beyond influenza: The process and data from 1 year of implementation in Vietnam.

PubMed

Alroy, Karen A; Do, Trang Thuy; Tran, Phu Dac; Dang, Tan Quang; Vu, Long Ngoc; Le, Nga Thi Hang; Dang, Anh Duc; Ngu, Nghia Duy; Ngo, Tu Huy; Hoang, Phuong Vu Mai; Phan, Lan Trong; Nguyen, Thuong Vu; Nguyen, Long Thanh; Nguyen, Thinh Viet; Vien, Mai Quang; Le, Huy Xuan; Dao, Anh The; Nguyen, Trieu Bao; Pham, Duoc Tho; Nguyen, Van Thi Tuyet; Pham, Thanh Ngoc; Phan, Binh Hai; Whitaker, Brett; Do, Thuy Thi Thu; Dao, Phuong Anh; Balajee, S Arunmozhi; Mounts, Anthony W

2018-05-13

In 2016, as a component of the Global Health Security Agenda, the Vietnam Ministry of Health expanded its existing influenza sentinel surveillance for severe acute respiratory infections (SARI) to include testing for 7 additional viral respiratory pathogens. This article describes the steps taken to implement expanded SARI surveillance in Vietnam and reports data from 1 year of expanded surveillance. The process of expanding the suite of pathogens for routine testing by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) included laboratory trainings, procurement/distribution of reagents, and strengthening and aligning SARI surveillance epidemiology practices at sentinel sites and regional institutes (RI). Surveillance data showed that of 4003 specimens tested by the RI laboratories, 20.2% (n = 810) were positive for influenza virus. Of the 3193 influenza-negative specimens, 41.8% (n = 1337) were positive for at least 1 non-influenza respiratory virus, of which 16.2% (n = 518), 13.4% (n = 428), and 9.6% (n = 308) tested positive for respiratory syncytial virus, rhinovirus, and adenovirus, respectively. The Government of Vietnam has demonstrated that expanding respiratory viral surveillance by strengthening and building upon an influenza platform is feasible, efficient, and practical. © 2018 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Reduction of a linear complex model for respiratory system during Airflow Interruption.

PubMed

Jablonski, Ireneusz; Mroczka, Janusz

2010-01-01

The paper presents methodology of a complex model reduction to its simpler version - an identifiable inverse model. Its main tool is a numerical procedure of sensitivity analysis (structural and parametric) applied to the forward linear equivalent designed for the conditions of interrupter experiment. Final result - the reduced analog for the interrupter technique is especially worth of notice as it fills a major gap in occlusional measurements, which typically use simple, one- or two-element physical representations. Proposed electrical reduced circuit, being structural combination of resistive, inertial and elastic properties, can be perceived as a candidate for reliable reconstruction and quantification (in the time and frequency domain) of dynamical behavior of the respiratory system in response to a quasi-step excitation by valve closure.

Bnip3 mediates doxorubicin-induced cardiac myocyte necrosis and mortality through changes in mitochondrial signaling

PubMed Central

Dhingra, Rimpy; Margulets, Victoria; Chowdhury, Subir Roy; Thliveris, James; Jassal, Davinder; Fernyhough, Paul; Dorn, Gerald W.; Kirshenbaum, Lorrie A.

2014-01-01

Doxorubicin (DOX) is widely used for treating human cancers, but can induce heart failure through an undefined mechanism. Herein we describe a previously unidentified signaling pathway that couples DOX-induced mitochondrial respiratory chain defects and necrotic cell death to the BH3-only protein Bcl-2-like 19kDa-interacting protein 3 (Bnip3). Cellular defects, including vacuolization and disrupted mitochondria, were observed in DOX-treated mice hearts. This coincided with mitochondrial localization of Bnip3, increased reactive oxygen species production, loss of mitochondrial membrane potential, mitochondrial permeability transition pore opening, and necrosis. Interestingly, a 3.1-fold decrease in maximal mitochondrial respiration was observed in cardiac mitochondria of mice treated with DOX. In vehicle-treated control cells undergoing normal respiration, the respiratory chain complex IV subunit 1 (COX1) was tightly bound to uncoupling protein 3 (UCP3), but this complex was disrupted in cells treated with DOX. Mitochondrial dysfunction induced by DOX was accompanied by contractile failure and necrotic cell death. Conversely, shRNA directed against Bnip3 or a mutant of Bnip3 defective for mitochondrial targeting abrogated DOX-induced loss of COX1-UCP3 complexes and respiratory chain defects. Finally, Bnip3−/− mice treated with DOX displayed relatively normal mitochondrial morphology, respiration, and mortality rates comparable to those of saline-treated WT mice, supporting the idea that Bnip3 underlies the cardiotoxic effects of DOX. These findings reveal a new signaling pathway in which DOX-induced mitochondrial respiratory chain defects and necrotic cell death are mutually dependent on and obligatorily linked to Bnip3 gene activation. Interventions that antagonize Bnip3 may prove beneficial in preventing mitochondrial injury and heart failure in cancer patients undergoing chemotherapy. PMID:25489073

Effect of chronic pre-treatment with angiotensin converting enzyme inhibition on skeletal muscle mitochondrial recovery after ischemia/reperfusion.

PubMed

Thaveau, Fabien; Zoll, Joffrey; Bouitbir, Jamal; N'guessan, Benoît; Plobner, Philippe; Chakfe, Nabil; Kretz, Jean-Georges; Richard, Ruddy; Piquard, François; Geny, Bernard

2010-06-01

Impaired skeletal muscle energetic participates in peripheral arterial disease (PAD) patient's morbidity and mortality. Angiotensin converting enzyme inhibition (ACEi), cornerstone for pharmacologic risk factor management in PAD patients, might also be interesting by protecting skeletal muscle energetic. We therefore determined whether chronic ACEi might reduce ischemia-induced mitochondrial respiratory chain dysfunction in the frequent setting of hindlimb ischemia-reperfusion. Ischemic legs of rats submitted to 5 h ischemia induced by a rubber band tourniquet applied on the root of the hindlimb followed by reperfusion without (IR, n = 11) or after ACEi (n = 14; captopril 40 mg/kg per day during 28 days before surgery) were studied and compared to that of sham-operated animals (n = 11). The effect of ACEi on the non-ischemic contralateral leg was also determined in the ACEi group. Maximal oxidative capacities (V(max)) and complexes I, II and IV activities of the mitochondrial respiratory chain of the gastrocnemius muscle were determined using glutamate-malate, succinate and TMPD-ascorbate substrates. Arterial blood pressure was significantly decreased after ACEi (124 +/- 2.8 vs. 108 +/- 4.19 mmHg; P = 0.01). Ischemia-reperfusion reduced V(max) (4.4 +/- 0.4 vs. 8.7 +/- 0.5 micromol O2/min/g dry weight, -49%, P < 0.001), affecting mitochondrial complexes I, II and IV activities. ACEi failed to modulate ischemia-induced dysfunction (V(max) 5.1 +/- 0.7 micromol O2/min/g dry weight) or the non-ischemic contralateral muscle respiratory rate. Ischemia-reperfusion significantly impaired the mitochondrial respiratory chain I, II and IV complexes of skeletal muscle. Pharmacologic pre-treatment with ACEi did not prevent or increase such alterations. Further studies might be useful to improve the pharmacologic conditioning of PAD patients needing arterial revascularization.

Extensive respiratory chain defects in inhibitory interneurones in patients with mitochondrial disease.

PubMed

Lax, Nichola Z; Grady, John; Laude, Alex; Chan, Felix; Hepplewhite, Philippa D; Gorman, Grainne; Whittaker, Roger G; Ng, Yi; Cunningham, Mark O; Turnbull, Doug M

2016-02-01

Mitochondrial disorders are among the most frequently inherited cause of neurological disease and arise due to mutations in mitochondrial or nuclear DNA. Currently, we do not understand the specific involvement of certain brain regions or selective neuronal vulnerability in mitochondrial disease. Recent studies suggest γ-aminobutyric acid (GABA)-ergic interneurones are particularly susceptible to respiratory chain dysfunction. In this neuropathological study, we assess the impact of mitochondrial DNA defects on inhibitory interneurones in patients with mitochondrial disease. Histochemical, immunohistochemical and immunofluorescent assays were performed on post-mortem brain tissue from 10 patients and 10 age-matched control individuals. We applied a quantitative immunofluorescent method to interrogate complex I and IV protein expression in mitochondria within GABAergic interneurone populations in the frontal, temporal and occipital cortices. We also evaluated the density of inhibitory interneurones in serial sections to determine if cell loss was occurring. We observed significant, global reductions in complex I expression within GABAergic interneurones in frontal, temporal and occipital cortices in the majority of patients. While complex IV expression is more variable, there is reduced expression in patients harbouring m.8344A>G point mutations and POLG mutations. In addition to the severe respiratory chain deficiencies observed in remaining interneurones, quantification of GABAergic cell density showed a dramatic reduction in cell density suggesting interneurone loss. We propose that the combined loss of interneurones and severe respiratory deficiency in remaining interneurones contributes to impaired neuronal network oscillations and could underlie development of neurological deficits, such as cognitive impairment and epilepsy, in mitochondrial disease. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Biogenesis of mitochondria in cauliflower (Brassica oleracea var. botrytis) curds subjected to temperature stress and recovery involves regulation of the complexome, respiratory chain activity, organellar translation and ultrastructure.

PubMed

Rurek, Michal; Woyda-Ploszczyca, Andrzej M; Jarmuszkiewicz, Wieslawa

2015-01-01

The biogenesis of the cauliflower curd mitochondrial proteome was investigated under cold, heat and the recovery. For the first time, two dimensional fluorescence difference gel electrophoresis was used to study the plant mitochondrial complexome in heat and heat recovery. Particularly, changes in the complex I and complex III subunits and import proteins, and the partial disintegration of matrix complexes were observed. The presence of unassembled subunits of ATP synthase was accompanied by impairment in mitochondrial translation of its subunit. In cold and heat, the transcription profiles of mitochondrial genes were uncorrelated. The in-gel activities of respiratory complexes were particularly affected after stress recovery. Despite a general stability of respiratory chain complexes in heat, functional studies showed that their activity and the ATP synthesis yield were affected. Contrary to cold stress, heat stress resulted in a reduced efficiency of oxidative phosphorylation likely due to changes in alternative oxidase (AOX) activity. Stress and stress recovery differently modulated the protein level and activity of AOX. Heat stress induced an increase in AOX activity and protein level, and AOX1a and AOX1d transcript level, while heat recovery reversed the AOX protein and activity changes. Conversely, cold stress led to a decrease in AOX activity (and protein level), which was reversed after cold recovery. Thus, cauliflower AOX is only induced by heat stress. In heat, contrary to the AOX activity, the activity of rotenone-insensitive internal NADH dehydrogenase was diminished. The relevance of various steps of plant mitochondrial biogenesis to temperature stress response and recovery is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

A Study of metabolic transformation of organic and inorganic components in PM2.5 and PM10, South Korea

NASA Astrophysics Data System (ADS)

Kim, J.; Yoon, H.; Lee, M.

2012-12-01

The important factors of atmospheric particle matter (PM) are size, concentration, composition and toxicity which can considerably affect the possible human health problem, especially respiratory diseases, visibility reduction and climate change. PM2.5 and PM10 are complex mixture of ammonium sulfate, ammonium nitrate, organic carbon, inorganic carbon and inorganic constituents. Recently, most researches of source attribution and assessments of the relationship between health effects and particle concentrations have not taken advantage of the development in analytical tools measuring the detailed molecular structure and microstructure of particles and of the knowledge of particle formation mechanisms in combustion system. This study will combine variety analytical techniques that can provide structural and compositional information to determine the correlation between sources of hazardous material and physicochemical properties in aerosol particle. Inorganic metal can be rapidly quantifying to filter base using ED-XRF (Energy-dispersive X-ray fluorescence). Speciation and quantification of water soluble components applied HPLC-ICP-MS and LC-MS NMR (nuclear magnetic resonance). Afterward, we investigate metabolic transformations of atmospheric particle matter also using FE-TEM (Field Emission Transmission Electron Microscopy).

The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria.

PubMed

Juzyszyn, Z; Czerny, B; Myśliwiec, Z; Pawlik, A; Droździk, M

2010-06-01

The effect of artichoke extract on mitochondrial respiratory chain (MRC) activity in isolated rat liver mitochondria (including reaction kinetics) was studied. The effect of the extract on the activity of isolated cytochrome oxidase was also studied. Extract in the range of 0.68-2.72 microg/ml demonstrated potent and concentration-dependent inhibitory activity. Concentrations > or =5.4 microg/ml entirely inhibited MRC activity. The succinate oxidase system (MRC complexes II-IV) was the most potently inhibited, its activity at an extract concentration of 1.36 microg/ml being reduced by 63.3% compared with the control (p < 0.05). The results suggest a complex inhibitory mechanism of the extract. Inhibition of the succinate oxidase system was competitive (K(i) = 0.23 microg/ml), whereas isolated cytochrome oxidase was inhibited noncompetitively (K(i) = 126 microg/ml). The results of this study suggest that the salubrious effects of artichoke extracts may rely in part on the effects of their active compounds on the activity of the mitochondrial respiratory chain system.

Report of the European Respiratory Society/European Cystic Fibrosis Society task force on the care of adults with cystic fibrosis.

PubMed

Elborn, J Stuart; Bell, Scott C; Madge, Susan L; Burgel, Pierre-Regis; Castellani, Carlo; Conway, Steven; De Rijcke, Karleen; Dembski, Birgit; Drevinek, Pavel; Heijerman, Harry G M; Innes, J Alistair; Lindblad, Anders; Marshall, Bruce; Olesen, Hanne V; Reimann, Andreas L; Solé, Ampara; Viviani, Laura; Wagner, Thomas O F; Welte, Tobias; Blasi, Francesco

2016-02-01

The improved survival in people with cystic fibrosis has led to an increasing number of patients reaching adulthood. This trend is likely to be maintained over the next decades, suggesting a need to increase the number of centres with expertise in the management of adult patients with cystic fibrosis. These centres should be capable of delivering multidisciplinary care addressing the complexity of the disease, in addition to addressing the psychological burden on patients and their families. Further issues that require attention are organ transplantation and end of life management.Lung disease in adults with cystic fibrosis drives most of the clinical care requirements, and major life-threatening complications, such as respiratory infection, respiratory failure, pneumothorax and haemoptysis, and the management of lung transplantation require expertise from trained respiratory physicians. The taskforce therefore strongly reccommends that medical leadership in multidisciplinary adult teams should be attributed to a respiratory physician adequately trained in cystic fibrosis management.The task force suggests the implementation of a core curriculum for trainees in adult respiratory medicine and the selection and accreditation of training centres that deliver postgraduate training to the standards of the HERMES programme. Copyright ©ERS 2016.

Cumulative lesioning of respiratory interneurons disrupts and precludes motor rhythms in vitro

PubMed Central

Hayes, John A.; Wang, Xueying; Del Negro, Christopher A.

2012-01-01

How brain functions degenerate in the face of progressive cell loss is an important issue that pertains to neurodegenerative diseases and basic properties of neural networks. We developed an automated system that uses two-photon microscopy to detect rhythmic neurons from calcium activity, and then individually laser ablates the targets while monitoring network function in real time. We applied this system to the mammalian respiratory oscillator located in the pre-Bötzinger Complex (preBötC) of the ventral medulla, which spontaneously generates breathing-related motor activity in vitro. Here, we show that cumulatively deleting preBötC neurons progressively decreases respiratory frequency and the amplitude of motor output. On average, the deletion of 120 ± 45 neurons stopped spontaneous respiratory rhythm, and our data suggest ≈82% of the rhythm-generating neurons remain unlesioned. Cumulative ablations in other medullary respiratory regions did not affect frequency but diminished the amplitude of motor output to a lesser degree. These results suggest that the preBötC can sustain insults that destroy no more than ≈18% of its constituent interneurons, which may have implications for the onset of respiratory pathologies in disease states. PMID:22566628

The mammalian respiratory system and critical windows of exposure for children's health.

PubMed Central

Pinkerton, K E; Joad, J P

2000-01-01

The respiratory system is a complex organ system composed of multiple cell types involved in a variety of functions. The development of the respiratory system occurs from embryogenesis to adult life, passing through several distinct stages of maturation and growth. We review embryonic, fetal, and postnatal phases of lung development. We also discuss branching morphogenesis and cellular differentiation of the respiratory system, as well as the postnatal development of xenobiotic metabolizing systems within the lungs. Exposure of the respiratory system to a wide range of chemicals and environmental toxicants during perinatal life has the potential to significantly affect the maturation, growth, and function of this organ system. Although the potential targets for exposure to toxic factors are currently not known, they are likely to affect critical molecular signals expressed during distinct stages of lung development. The effects of exposure to environmental tobacco smoke during critical windows of perinatal growth are provided as an example leading to altered cellular and physiological function of the lungs. An understanding of critical windows of exposure of the respiratory system on children's health requires consideration that lung development is a multistep process and cannot be based on studies in adults. Images Figure 1 Figure 4 PMID:10852845

Respiratory manifestations of panic disorder in animals and humans: a unique opportunity to understand how supramedullary structures regulate breathing.

PubMed

Kinkead, Richard; Tenorio, Luana; Drolet, Guy; Bretzner, Frédéric; Gargaglioni, Luciane

2014-12-01

The control of breathing is commonly viewed as being a "brainstem affair". As the topic of this special issue of Respiratory Physiology and Neurobiology indicates, we should consider broadening this notion since the act of breathing is also tightly linked to many functions other than close regulation of arterial blood gases. Accordingly, "non-brainstem" structures can exert a powerful influence on the core elements of the respiratory control network and as it is often the case, the importance of these structures is revealed when their dysfunction leads to disease. There is a clear link between respiration and anxiety and key theories of the psychopathology of anxiety (including panic disorders; PD) focus on respiratory control and related CO2 monitoring system. With that in mind, we briefly present the respiratory manifestations of panic disorder and discuss the role of the dorso-medial/perifornical hypothalamus, the amygdalar complex, and the periaqueductal gray in respiratory control. We then present recent advances in basic research indicating how adult rodent previously subjected to neonatal stress may provide a very good model to investigate the pathophysiology of PD. Copyright © 2014 Elsevier B.V. All rights reserved.

A respiratory alert model for the Shenandoah Valley, Virginia, USA

NASA Astrophysics Data System (ADS)

Hondula, David M.; Davis, Robert E.; Knight, David B.; Sitka, Luke J.; Enfield, Kyle; Gawtry, Stephen B.; Stenger, Phillip J.; Deaton, Michael L.; Normile, Caroline P.; Lee, Temple R.

2013-01-01

Respiratory morbidity (particularly COPD and asthma) can be influenced by short-term weather fluctuations that affect air quality and lung function. We developed a model to evaluate meteorological conditions associated with respiratory hospital admissions in the Shenandoah Valley of Virginia, USA. We generated ensembles of classification trees based on six years of respiratory-related hospital admissions (64,620 cases) and a suite of 83 potential environmental predictor variables. As our goal was to identify short-term weather linkages to high admission periods, the dependent variable was formulated as a binary classification of five-day moving average respiratory admission departures from the seasonal mean value. Accounting for seasonality removed the long-term apparent inverse relationship between temperature and admissions. We generated eight total models specific to the northern and southern portions of the valley for each season. All eight models demonstrate predictive skill (mean odds ratio = 3.635) when evaluated using a randomization procedure. The predictor variables selected by the ensembling algorithm vary across models, and both meteorological and air quality variables are included. In general, the models indicate complex linkages between respiratory health and environmental conditions that may be difficult to identify using more traditional approaches.

How should COPD patients exercise during respiratory rehabilitation? Comparison of exercise modalities and intensities to treat skeletal muscle dysfunction

PubMed Central

Puhan, M; Schunemann, H; Frey, M; Scharplatz, M; Bachmann, L

2005-01-01

Background: Physical exercise is an important component of respiratory rehabilitation because it reverses skeletal muscle dysfunction, a clinically important manifestation of COPD associated with reduced health-related quality of life (HRQL) and survival. However, there is controversy regarding the components of the optimal exercise protocol. A study was undertaken to systematically evaluate and summarise randomised controlled trials (RCTs) comparing different exercise protocols for COPD patients. Methods: Six electronic databases, congress proceedings and bibliographies of included studies were searched without imposing language restrictions. Two reviewers independently screened all records and extracted data on study samples, interventions and methodological characteristics of included studies. Results: The methodological quality of the 15 included RCTs was low to moderate. Strength exercise led to larger improvements of HRQL than endurance exercise (weighted mean difference for Chronic Respiratory Questionnaire 0.27, 95% CI 0.02 to 0.52). Interval exercise seems to be of similar effectiveness as continuous exercise, but there are few data on clinically relevant outcomes. One small RCT which included patients with mild COPD compared the effect of high and low intensity exercise (at 80% and 40% of the maximum exercise capacity, respectively) and found larger physiological training effects from high intensity exercise. Conclusions: Strength exercise should be routinely incorporated in respiratory rehabilitation. There is insufficient evidence to recommend high intensity exercise for COPD patients and investigators should conduct larger high quality trials to evaluate exercise intensities in patients with moderate to severe COPD. PMID:15860711

Development of a blunt chest injury care bundle: An integrative review.

PubMed

Kourouche, Sarah; Buckley, Thomas; Munroe, Belinda; Curtis, Kate

2018-06-01

Blunt chest injuries (BCI) are associated with high rates of morbidity and mortality. There are many interventions for BCI which may be able to be combined as a care bundle for improved and more consistent outcomes. To review and integrate the BCI management interventions to inform the development of a BCI care bundle. A structured search of the literature was conducted to identify studies evaluating interventions for patients with BCI. Databases MEDLINE, CINAHL, PubMed and Scopus were searched from 1990-April 2017. A two-step data extraction process was conducted using pre-defined data fields, including research quality indicators. Each study was appraised using a quality assessment tool, scored for level of evidence, then data collated into categories. Interventions were also assessed using the APEASE criteria then integrated to develop a BCI care bundle. Eighty-one articles were included in the final analysis. Interventions that improved BCI outcomes were grouped into three categories; respiratory intervention, analgesia and surgical intervention. Respiratory interventions included continuous positive airway pressure and high flow nasal oxygen. Analgesia interventions included regular multi-modal analgesia and paravertebral or epidural analgesia. Surgical fixation was supported for use in moderate to severe rib fractures/BCI. Interventions supported by evidence and that met APEASE criteria were combined into a BCI care bundle with four components: respiratory adjuncts, analgesia, complication prevention, and surgical fixation. The key components of a BCI care bundle are respiratory support, analgesia, complication prevention including chest physiotherapy and surgical fixation. Copyright © 2018 Elsevier Ltd. All rights reserved.

[CHANGE OF CHARACTER OF INTERSYSTEMIC INTERACTIONS IN NEWBORN RAT PUPS UNDER CONDITIONS OF A DECREASE OF MOTOR ACTIVITY].

PubMed

Sizonov, V A; Dmitrieva, L E; Kuznetsov, S V

2015-01-01

Interaction of slow-wave.rhythmic components of cardiac, respiratory.and motor activity was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) produced by injecting myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) dosages. The data obtained allow to infer that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of about-one- and many-minute ranges whereas the rhythms of decasecond range do not play a significant role in integrative processes. Injection of miocuran at a dose causing no muscle relaxation and no inhibition of motor activity produces changes of the cardiac and respiratory rhythms as well as a transitory decrease of the magnitude of coordinate relations mediated by the rhythms of about-one- and many-minute ranges. The consequences of muscle relaxant injection were found to be more significant for intersystemic interactions with participation of the respiratory system. An increase of the dosage and, correspondingly, the total inhibition of SPMA is accompanied by reduction of the slow-wave components from the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more expressed in intact rat pups, are reduced in the about-one- and many-minute ranges of modulation whereas in the decasecond range of modulation they are slightly increased. Key words: early ontogenesis, intersystemic interactions, cardiac rhythm, respiration, motor activity, myocuran (myanesin).

Gene silencing in the therapy of influenza and other respiratory diseases: Targeting to RNase P by use of External Guide Sequences (EGS)

PubMed Central

Dreyfus, David H; Tompkins, S Mark; Fuleihan, Ramsay; Ghoda, Lucy Y

2007-01-01

Respiratory diseases provide an attractive target for gene silencing using small nucleic acids since the respiratory epithelium can be reached by inhalation therapy. Natural surfactant appears to facilitate the uptake and distribution of these types of molecules making aerosolized nucleic acids a possible new class of therapeutics. This article will review the rationale for the use of External Guide Sequence (EGS) in targeting specific mRNA molecules for RNase P-mediated intracellular destruction. Specific destruction of target mRNA results in gene-specific silencing similar to that instigated by siRNA via the RISC complex. The application of EGS molecules specific for influenza genes are discussed as well as the potential for synergy with siRNA. Furthermore, EGS could be adapted to target other respiratory diseases of viral etiology as well as conditions such as asthma. PMID:19707312

Respiratory factors in the uptake and excretion of anesthetics. 1965.

PubMed

Epstein, R M; Papper, E M

1998-01-01

We have considered some of the ways in which respiration can affect the gas exchange process. The simplest relationships are purely physical and relate to the speed with which the lung and tissues can be filled or emptied. More complex relationships involve a consideration of the interplay between blood and gas in the lung and the effects of gas exchange on respiratory volumes themselves. Finally, some examples of the importance of physiologic alteration produced by, and producing respiratory shifts during, gas uptake processes were presented briefly. The detailed interpretation of gas exchange phenomena demands more quantitative information of this sort, concerning not only the respiratory but the circulatory and tissue level variations affecting uptake during anesthesia. Nevertheless, understanding of the principles and application of such data as are available can go far toward removing the handicaps of empirical practice from the day-to-day administration of anesthetic agents to human beings.