Complex systems in pulmonary medicine: a systems biology approach to lung disease

2011 ◽  
Vol 110 (6) ◽  
pp. 1716-1722 ◽  
Author(s):  
David A. Kaminsky ◽  
Charles G. Irvin ◽  
Peter J. Sterk
Keyword(s):  
Systems Biology ◽  
Lung Disease ◽  
Clinical Medicine ◽  
Molecular Genetic ◽  
Whole Body ◽  
Pulmonary Medicine ◽  
Pulmonary Physiology ◽  
The Many ◽  
And Function ◽  
Work Done

The lung is a highly complex organ that can only be understood by integrating the many aspects of its structure and function into a comprehensive view. Such a view is provided by a systems biology approach, whereby the many layers of complexity, from the molecular genetic, to the cellular, to the tissue, to the whole organ, and finally to the whole body, are synthesized into a working model of understanding. The systems biology approach therefore relies on the expertise of many disciplines, including genomics, proteomics, metabolomics, physiomics, and, ultimately, clinical medicine. The overall structure and functioning of the lung cannot be predicted from studying any one of these systems in isolation, and so this approach highlights the importance of emergence as the fundamental feature of systems biology. In this paper, we will provide an overview of a systems biology approach to lung disease by briefly reviewing the advances made at many of these levels, with special emphasis on recent work done in the realm of pulmonary physiology and the analysis of clinical phenotypes.

Hormonal synergism in mammary growth

1958 ◽  
Vol 149 (936) ◽  
pp. 303-325 ◽  
Keyword(s):  
Mammary Gland ◽  
Hormonal Control ◽  
The Past ◽  
Hormone Research ◽  
Long Time ◽  
Proper Perspective ◽  
The Many ◽  
And Function ◽  
The University ◽  
Work Done

Much of this report will consist of a summary of the mammary work done in the Department of Anatomy during the past 25 years in collaboration with Professor H. M. Evans’s group in the Institute of Experimental Biology and Professor Choh Hao Li of the Laboratory of Hormone Research, all of the University of California. Such a summary may be made most conveniently by using a schema and some photographs representing our main findings in the Long-Evans rat. The more difficult task is to fit this research into proper perspective involving, as it must, some reference to a mass of literature on the mammary gland. Rather than attempt a thorough review of the thousands of papers in this field, relatively few key examples have been chosen to indicate the trend of thought and theory during and just preceding the period of our investigations. For more complete reviews on this subject the reader is referred to Mayer & Klein (1948, 1949), Cowie & Folley (1955) and Folley (1956). Of historical interest is de Rothschild’s (1900) list of about 10 000 references to the literature prior to 1900, with supplements in 1901 and 1902. If a quarter of a century seems a long time to be engaged in elucidating the problem of hormonal control of the mammary gland, some explanation may be found in the fact that this was the period of isolation of the many hormones involved, and of developing satisfactory techniques for multiple endocrinectomies. That the problem would become a complicated one might have been suspected from the knowledge that the mammary gland arrived late, if not last, in the phylogenetic scale of organ evolution. Further, proof that such suspicion was well founded has been adduced in the many experiments showing that the main phases of mammary growth and function are dependent upon all of the hypophysial hormones and their target organ hormones, plus the secretions of that latest arrival on the endocrine scene—the placenta.

scholarly journals The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia

2020 ◽  
Vol 22 (1) ◽  
pp. 91
Author(s):  
Vanina Romanello
Keyword(s):  
Mitochondrial Dysfunction ◽  
Poor Quality ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Mitochondrial Morphology ◽  
Mass Force ◽  
Major Mechanism ◽  
Muscle Aging ◽  
And Function

Sarcopenia is a chronic disease characterized by the progressive loss of skeletal muscle mass, force, and function during aging. It is an emerging public problem associated with poor quality of life, disability, frailty, and high mortality. A decline in mitochondria quality control pathways constitutes a major mechanism driving aging sarcopenia, causing abnormal organelle accumulation over a lifetime. The resulting mitochondrial dysfunction in sarcopenic muscles feedbacks systemically by releasing the myomitokines fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), influencing the whole-body homeostasis and dictating healthy or unhealthy aging. This review describes the principal pathways controlling mitochondrial quality, many of which are potential therapeutic targets against muscle aging, and the connection between mitochondrial dysfunction and the myomitokines FGF21 and GDF15 in the pathogenesis of aging sarcopenia.

scholarly journals Spanning the gap: unraveling RSC dynamics in vivo

2021 ◽  
Author(s):  
Heinz Neumann ◽  
Bryan J. Wilkins
Keyword(s):  
Cell Cycle ◽  
Posttranslational Modifications ◽  
Transcriptional Activation ◽  
Binding Mode ◽  
Binding Modes ◽  
Binding Domains ◽  
Binding Interface ◽  
The Many ◽  
And Function

AbstractMultiple reports over the past 2 years have provided the first complete structural analyses for the essential yeast chromatin remodeler, RSC, providing elaborate molecular details for its engagement with the nucleosome. However, there still remain gaps in resolution, particularly within the many RSC subunits that harbor histone binding domains.Solving contacts at these interfaces is crucial because they are regulated by posttranslational modifications that control remodeler binding modes and function. Modifications are dynamic in nature often corresponding to transcriptional activation states and cell cycle stage, highlighting not only a need for enriched spatial resolution but also temporal understanding of remodeler engagement with the nucleosome. Our recent work sheds light on some of those gaps by exploring the binding interface between the RSC catalytic motor protein, Sth1, and the nucleosome, in the living nucleus. Using genetically encoded photo-activatable amino acids incorporated into histones of living yeast we are able to monitor the nucleosomal binding of RSC, emphasizing the regulatory roles of histone modifications in a spatiotemporal manner. We observe that RSC prefers to bind H2B SUMOylated nucleosomes in vivo and interacts with neighboring nucleosomes via H3K14ac. Additionally, we establish that RSC is constitutively bound to the nucleosome and is not ejected during mitotic chromatin compaction but alters its binding mode as it progresses through the cell cycle. Our data offer a renewed perspective on RSC mechanics under true physiological conditions.

scholarly journals Surfactant Composition and Function in a Primate Model of Infant Chronic Lung Disease: Effects of Inhaled Nitric Oxide

2006 ◽  
Vol 59 (1) ◽  
pp. 157-162 ◽  
Author(s):  
Philip L Ballard ◽  
Linda W Gonzales ◽  
Rodolfo I Godinez ◽  
Marye H Godinez ◽  
Rashmin C Savani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Inhaled Nitric Oxide ◽  
Primate Model ◽  
Surfactant Composition ◽  
And Function

THE CRITICALLY ILL CHILD: SICKLE CELL DISEASE CRISES AND THEIR MANAGEMENT

PEDIATRICS ◽  
1971 ◽  
Vol 48 (4) ◽  
pp. 629-635
Author(s):  
Howard A. Pearson ◽  
Louis K. Diamond
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mutant Gene ◽  
Point Of View ◽  
Clinical Aspects ◽  
Cell Disease ◽  
Form And Function ◽  
Heterozygous Form ◽  
The Many ◽  
And Function

This brief review, being limited in scope to the recognition and management of the life-threatening and painful crises in infants and children with sickle-cell disease, has not even touched on the intriguing mystery of the molecular basis for the sickling phenomenon–how one amino-acid substitution (gene controlled) in the beta chain sequence of 146 amino acids can cause such serious disruption in form and function; or how this mutation occurred in the first place and why it has persisted in contrast to the rapid disappearance of many other deleterious mutants. Nor has there been even mention of the many milder symptoms, signs, and complications due to the presence of Hb. S., either in the homozygous (disease-producing) state or heterozygous form when found in combination with other hereditary hemoglobin defects. The accumulated knowledge about this mutant gene, its biochemical effects, and geographic distribution is enormous. From a fundamental scientific standpoint, sickle cell disease is one of the best understood of human afflictions. However, from a practical point of view treatment of the patient himself is often only symptomatic and palliative. Nevertheless, prompt and effective therapy of the myriad manifestations of sickle cell disease can effectively reduce morbidity and mortality. The pediatrician who cares for black children in his practice should be familiar with the cardinal diagnostic and clinical aspects of sickle cell disease and its crises.

Flow-Volume Curves in Infants with Lung Disease

PEDIATRICS ◽  
1983 ◽  
Vol 72 (4) ◽  
pp. 517-522
Author(s):  
S. Godfrey ◽  
E. Bar-Yishay ◽  
I. Arad ◽  
L. I. Landau ◽  
L. M. Taussig
Keyword(s):  
Lung Disease ◽  
Airway Obstruction ◽  
Lung Volume ◽  
Airway Resistance ◽  
Whole Body ◽  
Small Airways ◽  
Forced Expiration ◽  
Flow Volume ◽  
Complete Evaluation ◽  
Expiratory Flow

Partial expiratory flow-volume maneuvers have been performed on nine occasions on six infants with a variety of pulmonary problems using a new tech nique for thoracic compression. The infants were placed within an inflatable bag that was, itself, within a canvas bag. By sudden controlled inflation of the inner bag at end inspiration, partial expiratory flow-volume curves were generated and recorded by means of a face mask and pneumotachograph. By comparing these flow results with those airway resistance and lung volume measurements obtained from the infants in whole body plethysmography and by noting the effect of inhaling a helium/oxygen gas mixture, it was possible to partition the airway obstruction between large and small airways. The presence of small airway obstruction was noted in the absence of changes in airway resistance or lung volume in several instances. A complete evaluation of airway function should include this test of forced expiration for greater understanding and treatment of lung disease in infancy.

Structure and Function of the Lateral Giant Neurone of the Primitive Crustacean Anaspides Tasmaniae

1979 ◽  
Vol 78 (1) ◽  
pp. 121-136
Author(s):  
GERALD E. SILVEY ◽  
IAN S. WILSON
Keyword(s):  
Action Potentials ◽  
Tactile Stimulation ◽  
Large Diameter ◽  
Whole Body ◽  
Giant Fibre ◽  
Single Action ◽  
Giant Neurone ◽  
And Function ◽  
Thoracic And Abdominal ◽  
Stimulation Of

The syncarid crustacean Anaspides tasmaniae rapidly flexes its free thoracic and abdominal segments in response to tactile stimulation of its body. This response decrements but recovers in slightly more than one hour. The fast flexion is evoked by single action potentials in the lateral of two large diameter fibres (40 μm) which lie on either side of the cord. The lateral giant fibre is made up of fused axons of 11 neurones, one in each of the last 5 thoracic and 6 abdominal ganglia. The soma of each neurone lies contralateral to the axon. Its neurite crosses that of its counterpart in the commissure and gives out dendrites into the neuropile of each hemiganglion. The lateral giant neurone receives input from the whole body but fires in response only to input from the fourth thoracic segment posteriorly. Both fibres respond with tactile stimulation of only one side. Since neither current nor action potentials spread from one fibre to the other, afferents must synapse with both giant neurones. The close morphological and physiological similarities of the lateral giant neurone in Anaspides to that in the crayfish (Eucarida) suggest that the lateral giant system arose in the ancestor common to syncarids and eucarids, prior to the Carboniferous.

Integrative Sleep Medicine

2021 ◽  
Keyword(s):  
Circadian Rhythm ◽  
Sleep Disorders ◽  
Health Care Providers ◽  
Sleep Disturbances ◽  
Well Being ◽  
Sleep Medicine ◽  
Whole Body ◽  
Care Providers ◽  
Obstructive Sleep ◽  
The Many

Sleep is one of the key underpinnings of human health, yet sleep disturbances and impaired sleep are rampant in modern life. Healthy sleep is a whole-body process impacted by circadian rhythm, daily activities, and emotional well-being, among others. When properly aligned, these work in concert to produce restorative and refreshing sleep. When not in balance, however, sleep disorders result. Yet too often, the approach to treatment of sleep disorders is compartmentalized, failing to recognize all of the complex interactions that are involved. This text offers a comprehensive approach to sleep and sleep disorders by delineating the many factors that interplay into healthy sleep. Health care providers can learn how to better manage their patients with sleep disorders by integrating complementary and conventional approaches. Using an evidence-based approach throughout, this book describes the basics of normal sleep then delves into the foundations of integrative sleep medicine, including the circadian rhythm, mind/body-sleep connection, light, dreaming, the gastrointestinal system, and botanicals/supplements. Specific sleep issues and disorders are then addressed from an integrative perspective, including insomnia, obstructive sleep apnea, sleep related movement disorders, and parasomnias.

A Systems Biology Approach for Understanding Granuloma Formation and Function in Tuberculosis

2012 ◽  
pp. 127-155 ◽  
Author(s):  
Mohammad Fallahi-Sichani ◽  
Simeone Marino ◽  
JoAnne L. Flynn ◽  
Jennifer J. Linderman ◽  
Denise E. Kirschner
Keyword(s):  
Systems Biology ◽  
Granuloma Formation ◽  
And Function
Sign in / Sign up

Export Citation Format

Share Document