Physiologically relevant organs on chips.

PubMed

Yum, Kyungsuk; Hong, Soon Gweon; Healy, Kevin E; Lee, Luke P

2014-01-01

Recent advances in integrating microengineering and tissue engineering have generated promising microengineered physiological models for experimental medicine and pharmaceutical research. Here we review the recent development of microengineered physiological systems, or also known as "ogans-on-chips", that reconstitute the physiologically critical features of specific human tissues and organs and their interactions. This technology uses microengineering approaches to construct organ-specific microenvironments, reconstituting tissue structures, tissue-tissue interactions and interfaces, and dynamic mechanical and biochemical stimuli found in specific organs, to direct cells to assemble into functional tissues. We first discuss microengineering approaches to reproduce the key elements of physiologically important, dynamic mechanical microenvironments, biochemical microenvironments, and microarchitectures of specific tissues and organs in microfluidic cell culture systems. This is followed by examples of microengineered individual organ models that incorporate the key elements of physiological microenvironments into single microfluidic cell culture systems to reproduce organ-level functions. Finally, microengineered multiple organ systems that simulate multiple organ interactions to better represent human physiology, including human responses to drugs, is covered in this review. This emerging organs-on-chips technology has the potential to become an alternative to 2D and 3D cell culture and animal models for experimental medicine, human disease modeling, drug development, and toxicology. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermal mechanisms of interaction of radiofrequency energy with biological systems with relevance to exposure guidelines.

PubMed

Foster, Kenneth R; Glaser, Roland

2007-06-01

This article reviews thermal mechanisms of interaction between radiofrequency (RF) fields and biological systems, focusing on theoretical frameworks that are of potential use in setting guidelines for human exposure to RF energy. Several classes of thermal mechanisms are reviewed that depend on the temperature increase or rate of temperature increase and the relevant dosimetric considerations associated with these mechanisms. In addition, attention is drawn to possible molecular and physiological reactions that could be induced by temperature elevations below 0.1 degrees, which are normal physiological responses to heat, and to the so-called microwave auditory effect, which is a physiologically trivial effect resulting from thermally-induced acoustic stimuli. It is suggested that some reported "nonthermal" effects of RF energy may be thermal in nature; also that subtle thermal effects from RF energy exist but have no consequence to health or safety. It is proposed that future revisions of exposure guidelines make more explicit use of thermal models and empirical data on thermal effects in quantifying potential hazards of RF fields.

Magnesium degradation under physiological conditions - Best practice.

PubMed

Gonzalez, Jorge; Hou, Rui Qing; Nidadavolu, Eshwara P S; Willumeit-Römer, Regine; Feyerabend, Frank

2018-06-01

This review focusses on the application of physiological conditions for the mechanistic understanding of magnesium degradation. Despite the undisputed relevance of simplified laboratory setups for alloy screening purposes, realistic and predictive in vitro setups are needed. Due to the complexity of these systems, the review gives an overview about technical measures, defines some caveats and can be used as a guideline for the establishment of harmonized laboratory approaches.

Human physiology in space

NASA Technical Reports Server (NTRS)

Vernikos, J.

1996-01-01

The universality of gravity (1 g) in our daily lives makes it difficult to appreciate its importance in morphology and physiology. Bone and muscle support systems were created, cellular pumps developed, neurons organised and receptors and transducers of gravitational force to biologically relevant signals evolved under 1g gravity. Spaceflight provides the only microgravity environment where systematic experimentation can expand our basic understanding of gravitational physiology and perhaps provide new insights into normal physiology and disease processes. These include the surprising extent of our body's dependence on perceptual information, and understanding the effect and importance of forces generated within the body's weightbearing structures such as muscle and bones. Beyond this exciting prospect is the importance of this work towards opening the solar system for human exploration. Although both appear promising, we are only just beginning to taste what lies ahead.

Overview of the Anatomy, Physiology, and Pharmacology of the Autonomic Nervous System.

PubMed

Wehrwein, Erica A; Orer, Hakan S; Barman, Susan M

2016-06-13

Comprised of the sympathetic nervous system, parasympathetic nervous system, and enteric nervous system, the autonomic nervous system (ANS) provides the neural control of all parts of the body except for skeletal muscles. The ANS has the major responsibility to ensure that the physiological integrity of cells, tissues, and organs throughout the entire body is maintained (homeostasis) in the face of perturbations exerted by both the external and internal environments. Many commonly prescribed drugs, over-the-counter drugs, toxins, and toxicants function by altering transmission within the ANS. Autonomic dysfunction is a signature of many neurological diseases or disorders. Despite the physiological relevance of the ANS, most neuroscience textbooks offer very limited coverage of this portion of the nervous system. This review article provides both historical and current information about the anatomy, physiology, and pharmacology of the sympathetic and parasympathetic divisions of the ANS. The ultimate aim is for this article to be a valuable resource for those interested in learning the basics of these two components of the ANS and to appreciate its importance in both health and disease. Other resources should be consulted for a thorough understanding of the third division of the ANS, the enteric nervous system. © 2016 American Physiological Society. Compr Physiol 6:1239-1278, 2016. Copyright © 2016 John Wiley & Sons, Inc.

A Database as a Service for the Healthcare System to Store Physiological Signal Data.

PubMed

Chang, Hsien-Tsung; Lin, Tsai-Huei

2016-01-01

Wearable devices that measure physiological signals to help develop self-health management habits have become increasingly popular in recent years. These records are conducive for follow-up health and medical care. In this study, based on the characteristics of the observed physiological signal records- 1) a large number of users, 2) a large amount of data, 3) low information variability, 4) data privacy authorization, and 5) data access by designated users-we wish to resolve physiological signal record-relevant issues utilizing the advantages of the Database as a Service (DaaS) model. Storing a large amount of data using file patterns can reduce database load, allowing users to access data efficiently; the privacy control settings allow users to store data securely. The results of the experiment show that the proposed system has better database access performance than a traditional relational database, with a small difference in database volume, thus proving that the proposed system can improve data storage performance.

A Database as a Service for the Healthcare System to Store Physiological Signal Data

PubMed Central

Lin, Tsai-Huei

2016-01-01

Wearable devices that measure physiological signals to help develop self-health management habits have become increasingly popular in recent years. These records are conducive for follow-up health and medical care. In this study, based on the characteristics of the observed physiological signal records– 1) a large number of users, 2) a large amount of data, 3) low information variability, 4) data privacy authorization, and 5) data access by designated users—we wish to resolve physiological signal record-relevant issues utilizing the advantages of the Database as a Service (DaaS) model. Storing a large amount of data using file patterns can reduce database load, allowing users to access data efficiently; the privacy control settings allow users to store data securely. The results of the experiment show that the proposed system has better database access performance than a traditional relational database, with a small difference in database volume, thus proving that the proposed system can improve data storage performance. PMID:28033415

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications.

PubMed

Schwitzer, Thomas; Schwan, Raymund; Angioi-Duprez, Karine; Giersch, Anne; Laprevote, Vincent

2016-01-01

Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.

Collection of annotated data in a clinical validation study for alarm algorithms in intensive care--a methodologic framework.

PubMed

Siebig, Sylvia; Kuhls, Silvia; Imhoff, Michael; Langgartner, Julia; Reng, Michael; Schölmerich, Jürgen; Gather, Ursula; Wrede, Christian E

2010-03-01

Monitoring of physiologic parameters in critically ill patients is currently performed by threshold alarm systems with high sensitivity but low specificity. As a consequence, a multitude of alarms are generated, leading to an impaired clinical value of these alarms due to reduced alertness of the intensive care unit (ICU) staff. To evaluate a new alarm procedure, we currently generate a database of physiologic data and clinical alarm annotations. Data collection is taking place at a 12-bed medical ICU. Patients with monitoring of at least heart rate, invasive arterial blood pressure, and oxygen saturation are included in the study. Numerical physiologic data at 1-second intervals, monitor alarms, and alarm settings are extracted from the surveillance network. Bedside video recordings are performed with network surveillance cameras. Based on the extracted data and the video recordings, alarms are clinically annotated by an experienced physician. The alarms are categorized according to their technical validity and clinical relevance by a taxonomy system that can be broadly applicable. Preliminary results showed that only 17% of the alarms were classified as relevant, and 44% were technically false. The presented system for collecting real-time bedside monitoring data in conjunction with video-assisted annotations of clinically relevant events is the first allowing the assessment of 24-hour periods and reduces the bias usually created by bedside observers in comparable studies. It constitutes the basis for the development and evaluation of "smart" alarm algorithms, which may help to reduce the number of alarms at the ICU, thereby improving patient safety. Copyright 2010 Elsevier Inc. All rights reserved.

The concept of function in modern physiology.

PubMed

Roux, Etienne

2014-06-01

An overview of the scientific literature shows that the concept of function is central in physiology. However, the concept itself is not defined by physiologists. On the other hand, the teleological, namely, the 'goal-directed' dimension of function, and its subsequent explanatory relevance, is a philosophical problem. Intuitively, the function of a trait in a system explains why this trait is present, but, in the early 1960s, Ernest Nagel and Carl Hempel have shown that this inference cannot be logically founded. However, they showed that self-regulated systems are teleological. According to the selectionist theories, the function of an item is its effect that has been selected by natural selection, a process that explains its presence. As they restrict the functional attribution of a trait to its past selective value and not its current properties, these theories are inconsistent with the concept of function in physiology. A more adequate one is the causal role theory, for which a function of a trait in a system is its causal contribution to the functional capacity of the system. However, this leaves unsolved the question of the 'surplus meaning' of the teleological dimension of function. The significance of considering organisms as 'purpose-like' (teleological) systems may reside not in its explanatory power but in its methodological fruitfulness in physiology. In this view, the teleological dimension of physiological functions is convergent to but not imported from, the teleological dimension of evolutionary biology. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Personality, emotion, and individual differences in physiological responses.

PubMed

Stemmler, Gerhard; Wacker, Jan

2010-07-01

A dominant paradigm in biopsychological personality research seeks to establish links between emotional and motivational traits and habitual, transsituationally consistent individual differences in measures of physiological activity. An alternative approach conceptualizes traits as dispositions that are only operative in certain situational contexts and consequently predicts associations between emotional and motivational traits and physiological activity only for trait-relevant situational contexts in which the physiological systems underlying the traits in question are engaged. In the present paper we first examine and contrast these personistic and interactionistic conceptualizations of personality and personality-physiology associations and then present data from several large studies (N>100) in which electrocortical (e.g., frontal alpha asymmetry) and somatovisceral parameters were measured in various situational contexts (e.g., after the induction of either anger, or fear, or anxiety). As predicted by the interactionistic conceptualization of traits as dispositions the situational context and its subjective representation by the participants moderated the personality-physiology relationships for measures of both central and peripheral nervous system activity. We conclude by outlining the implications of the interactionistic approach for biopsychological personality research. Copyright © 2009 Elsevier B.V. All rights reserved.

A Novel, Ecologically Relevant, Highly Preferred, and Non-invasive Means of Oral Substance Administration for Rodents

PubMed Central

Sobolewski, Marissa; Allen, Joshua L.; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A.

2017-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of xenobiotic administration that eliminates physiological alterations associated with other methods of delivery. PMID:27094606

A novel, ecologically relevant, highly preferred, and non-invasive means of oral substance administration for rodents.

PubMed

Sobolewski, Marissa; Allen, Joshua L; Morris-Schaffer, Keith; Klocke, Carolyn; Conrad, Katherine; Cory-Slechta, Deborah A

2016-01-01

Prenatal stress and nutrition are well-known to alter a broad range of physiological systems, notably metabolic, endocrine and neurobehavioral function. Commonly used methods for oral administration of xenobiotics can, by acting as a stressor or altering normal nutrition intake, alter these physiological systems as well. Taken together, oral administration methods may unintentionally introduce confounding physiological effects that can mask or enhance toxicity of xenobiotics, particularly if they share biological targets. Consequently, it should be preferable to develop alternative methods without these potential confounds. The aim of this study was to determine the suitability of mealworms as an alternative treat-based method to deliver xenobiotics via the orogastric route. Accurate oral administration is contingent on motivation and preference; mice reliably preferred mealworms over wafer cookie treats. Further, ingestion of wafer cookies significantly increased mouse blood glucose levels, whereas unaltered mealworms produced no such change. Mealworms functioned effectively to orally administer glucose, as glucose-spiked mealworms produced a rise in blood glucose equivalent to the ingestion of the wafer cookie. Mealworms did not interfere with the physiological function of orally administered d-amphetamine, as both mealworm and oral gavage administered d-amphetamine showed similar alterations in locomotor behavior (mice did not fully consume d-amphetamine-dosed cookies and thus could not be compared). Collectively, the findings indicate that mealworms are a preferred and readily consumed treat, which importantly mimics environmental-relevant nutritional intake, and mealworms per se do not alter glucose metabolic pathways. Additionally, mealworms accurately delivered xenobiotics into blood circulation and did not interfere with the physiological function of administered xenobiotics. Thus mealworm-based oral administration may be a preferable and accurate route of xenobiotic administration that eliminates physiological alterations associated with other methods of delivery. Copyright © 2016. Published by Elsevier Inc.

Applying systems biology methods to the study of human physiology in extreme environments

PubMed Central

2013-01-01

Systems biology is defined in this review as ‘an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems’. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling. PMID:23849719

Reviewing the relevance of fluorescence in biological systems.

PubMed

Lagorio, M Gabriela; Cordon, Gabriela B; Iriel, Analia

2015-09-26

Fluorescence is emitted by diverse living organisms. The analysis and interpretation of these signals may give information about their physiological state, ways of communication among species and the presence of specific chemicals. In this manuscript we review the state of the art in the research on the fluorescence emitted by plant leaves, fruits, flowers, avians, butterflies, beetles, dragonflies, millipedes, cockroaches, bees, spiders, scorpions and sea organisms and discuss its relevance in nature.

Overview of exocrine pancreatic pathobiology.

PubMed

Pandiri, Arun R

2014-01-01

Exocrine pancreas is a source of several enzymes that are essential for the digestive process. The exocrine pancreatic secretion is tightly regulated by the neuroendocrine system. The endocrine pancreas is tightly integrated anatomically and physiologically with the exocrine pancreas and modulates its function. Compound-induced pancreatitis is not a common event in toxicology or drug development, but it becomes a significant liability when encountered. Understanding the species-specific differences in physiology is essential to understand the underlying pathobiology of pancreatic disease in animal models and its relevance to human disease. This review will mainly focus on understanding the morphology and physiology of the pancreas, unique islet-exocrine interactions, and pancreatitis.

Biological properties of extracellular vesicles and their physiological functions

PubMed Central

Yáñez-Mó, María; Siljander, Pia R.-M.; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E.; Buzas, Edit I.; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Silva, Anabela Cordeiro-da; Fais, Stefano; Falcon-Perez, Juan M.; Ghobrial, Irene M.; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H. H.; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Hoen, Esther N.M. Nolte-‘t; Nyman, Tuula A.; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; del Portillo, Hernando A.; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N.; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G.; Vasconcelos, M. Helena; Wauben, Marca H. M.; De Wever, Olivier

2015-01-01

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. PMID:25979354

Biological properties of extracellular vesicles and their physiological functions.

PubMed

Yáñez-Mó, María; Siljander, Pia R-M; Andreu, Zoraida; Zavec, Apolonija Bedina; Borràs, Francesc E; Buzas, Edit I; Buzas, Krisztina; Casal, Enriqueta; Cappello, Francesco; Carvalho, Joana; Colás, Eva; Cordeiro-da Silva, Anabela; Fais, Stefano; Falcon-Perez, Juan M; Ghobrial, Irene M; Giebel, Bernd; Gimona, Mario; Graner, Michael; Gursel, Ihsan; Gursel, Mayda; Heegaard, Niels H H; Hendrix, An; Kierulf, Peter; Kokubun, Katsutoshi; Kosanovic, Maja; Kralj-Iglic, Veronika; Krämer-Albers, Eva-Maria; Laitinen, Saara; Lässer, Cecilia; Lener, Thomas; Ligeti, Erzsébet; Linē, Aija; Lipps, Georg; Llorente, Alicia; Lötvall, Jan; Manček-Keber, Mateja; Marcilla, Antonio; Mittelbrunn, Maria; Nazarenko, Irina; Nolte-'t Hoen, Esther N M; Nyman, Tuula A; O'Driscoll, Lorraine; Olivan, Mireia; Oliveira, Carla; Pállinger, Éva; Del Portillo, Hernando A; Reventós, Jaume; Rigau, Marina; Rohde, Eva; Sammar, Marei; Sánchez-Madrid, Francisco; Santarém, N; Schallmoser, Katharina; Ostenfeld, Marie Stampe; Stoorvogel, Willem; Stukelj, Roman; Van der Grein, Susanne G; Vasconcelos, M Helena; Wauben, Marca H M; De Wever, Olivier

2015-01-01

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Biomarkers and Environmental Stress: Relevance of Cellular Responses in Determining Adverse Outcomes

EPA Science Inventory

Biomarkers are measurable changes in a biological system indicative of an interaction with a chemical, physical, or biological agent. Such changes can be molecular, biochemical, physiological, or histological and can be reflective of either xenobiotic exposures or effects. Molecu...

WAT-on-a-chip: A physiologically relevant microfluidic system incorporating white adipose tissue

PubMed Central

Loskill, Peter; Sezhian, Thiagarajan; Tharp, Kevin; Lee-Montiel, Felipe T.; Jeeawoody, Shaheen; Reese, Willie Mae; Zushin, Pete-James H.; Stahl, Andreas; Healy, Kevin E.

2017-01-01

Organ-on-a-chip systems possess a promising future as drug screening assays and as testbeds for disease modeling in the context of both single-organ systems and multi-organ-chips. Although it comprises approximately one fourth of the body weight of a healthy human, an organ frequently overlooked in this context is white adipose tissue (WAT). WAT-on-a-chip systems are required to create safety profiles of a large number of drugs due to their interactions with adipose tissue and other organs via paracrine signals, fatty acid release, and drug levels through sequestration. We report a WAT-on-a-chip system with a footprint of less than 1 mm2 consisting of a separate media channel and WAT chamber connected via small micropores. Analogous to the in vivo blood circulation, convective transport is thereby confined to the vasculature-like structures and the tissues protected from shear stresses. Numerical and analytical modeling revealed that the flow rates in the WAT chambers are less than 1/100 of the input flow rate. Using optimized injection parameters, we were able to inject pre-adipocytes, which subsequently formed adipose tissue featuring fully functional lipid metabolism. The physiologically relevant microfluidic environment of the WAT-chip supported long term culture of the functional adipose tissue for more than two weeks. Due to its physiological, highly controlled, and computationally predictable character, the system has the potential to be a powerful tool for the study of adipose tissue associated diseases such as obesity and type 2 diabetes. PMID:28418430

ECVAM and new technologies for toxicity testing.

PubMed

Bouvier d'Yvoire, Michel; Bremer, Susanne; Casati, Silvia; Ceridono, Mara; Coecke, Sandra; Corvi, Raffaella; Eskes, Chantra; Gribaldo, Laura; Griesinger, Claudius; Knaut, Holger; Linge, Jens P; Roi, Annett; Zuang, Valérie

2012-01-01

The development of alternative empirical (testing) and non-empirical (non-testing) methods to traditional toxicological tests for complex human health effects is a tremendous task. Toxicants may potentially interfere with a vast number of physiological mechanisms thereby causing disturbances on various levels of complexity of human physiology. Only a limited number of mechanisms relevant for toxicity ('pathways' of toxicity) have been identified with certainty so far and, presumably, many more mechanisms by which toxicants cause adverse effects remain to be identified. Recapitulating in empirical model systems (i.e., in vitro test systems) all those relevant physiological mechanisms prone to be disturbed by toxicants and relevant for causing the toxicity effect in question poses an enormous challenge. First, the mechanism(s) of action of toxicants in relation to the most relevant adverse effects of a specific human health endpoint need to be identified. Subsequently, these mechanisms need to be modeled in reductionist test systems that allow assessing whether an unknown substance may operate via a specific (array of) mechanism(s). Ideally, such test systems should be relevant for the species of interest, i.e., based on human cells or modeling mechanisms present in humans. Since much of our understanding about toxicity mechanisms is based on studies using animal model systems (i.e., experimental animals or animal-derived cells), designing test systems that model mechanisms relevant for the human situation may be limited by the lack of relevant information from basic research. New technologies from molecular biology and cell biology, as well as progress in tissue engineering, imaging techniques and automated testing platforms hold the promise to alleviate some of the traditional difficulties associated with improving toxicity testing for complex endpoints. Such new technologies are expected (1) to accelerate the identification of toxicity pathways with human relevance that need to be modeled in test methods for toxicity testing (2) to enable the reconstruction of reductionist test systems modeling at a reduced level of complexity the target system/organ of interest (e.g., through tissue engineering, use of human-derived cell lines and stem cells etc.), (3) to allow the measurement of specific mechanisms relevant for a given health endpoint in such test methods (e.g., through gene and protein expression, changes in metabolites, receptor activation, changes in neural activity etc.), (4) to allow to measure toxicity mechanisms at higher throughput rates through the use of automated testing. In this chapter, we discuss the potential impact of new technologies on the development, optimization and use of empirical testing methods, grouped according to important toxicological endpoints. We highlight, from an ECVAM perspective, the areas of topical toxicity, skin absorption, reproductive and developmental toxicity, carcinogenicity/genotoxicity, sensitization, hematopoeisis and toxicokinetics and discuss strategic developments including ECVAM's database service on alternative methods. Neither the areas of toxicity discussed nor the highlighted new technologies represent comprehensive listings which would be an impossible endeavor in the context of a book chapter. However, we feel that these areas are of utmost importance and we predict that new technologies are likely to contribute significantly to test development in these fields. We summarize which new technologies are expected to contribute to the development of new alternative testing methods over the next few years and point out current and planned ECVAM projects for each of these areas.

Magnesium degradation observed in situ under flow by synchrotron radiation based microtomography

NASA Astrophysics Data System (ADS)

Feyerabend, Frank; Dose, Thomas; Xu, Yuling; Beckmann, Felix; Stekker, Michael; Willumeit-Römer, Regine; Schreyer, Andreas; Wilde, Fabian; Hammel, Jörg U.

2016-10-01

The use of degradable magnesium based implants is becoming clinically relevant, e.g. for the use as bone screws. Still there is a lack of analyzing techniques to characterize the in vitro degradation behavior of implant prototypes. The aim of this study was to design an in situ environment to continuously monitor the degradation processes under physiological conditions by time-lapse SRμCT. The use of physiological conditions was chosen to get a better approach to the in vivo situation, as it could be shown by many studies, that these conditions change on the one hand the degradation rate and on the other hand also the formed degradation products. The resulting in situ environment contains a closed bioreactor system to control and monitor the relevant parameters (37°C, 5 % O2, 20 % CO2) and to grant sterility of the setup. A flow cell was designed and manufactured from polyether etherketone (PEEK), which was chosen because of the good mechanical properties, high thermal and chemical resistance and radiographic translucency. Sterilization of the system including the sample was reached by a transient flush with 70 % ethanol and subsequent replacement by physiological medium (Modified Eagle Medium alpha). As proof of principle it could be shown that the system remained sterile during a beamtime of several days and that the continuous SRμCT imaging was feasible.

The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications

PubMed Central

Schwitzer, Thomas; Schwan, Raymund; Angioi-Duprez, Karine; Giersch, Anne; Laprevote, Vincent

2016-01-01

Cannabis is one of the most prevalent drugs used in industrialized countries. The main effects of Cannabis are mediated by two major exogenous cannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2. Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes. This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system. As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology. This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection. Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases. Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing. PMID:26881099

Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

PubMed

Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

2013-03-01

New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

[Clinical, morphological and molecular biological characteristics of the aging eye].

PubMed

Böhm, M R R; Thomasen, H; Parnitzke, F; Steuhl, K-P

2017-02-01

The physiological aging of the eye is associated with loss of visual function. Age-related changes of the eye can result in ophthalmological diseases. The aim of this article is to display morphological, histological and molecular biological alterations of the aging eye. A web-based search and review of the literature for aging of the visual system including cornea, lens, vitreous humor, retina, retinal pigment epithelium (RPE), choroidea and optic nerve were carried out. The most important results related to morphological, histological and molecular biological changes are summarized. Age-related, morphological alterations can be found in preretinal structures, e. g. cornea, lens and vitreous humor, as well as neuronal structures, such as the retina. In addition to negligible clinical signs of the aging eye, there are clinically relevant changes which can develop into pathological ophthalmological diseases. These transitions from age-related alterations to relevant ophthalmological diseases, e. g. age-related macular degeneration and glaucoma are continuous. An understanding of aging could provide predictive factors to detect the conversion of physiological aging into pathological conditions. The derivation of physiological markers or new approaches to detection and treatment of disease-related entities associated with the risk factor aging are desirable. Translational approaches in clinical and basic science are necessary to provide new therapeutic options for relevant ophthalmological diseases in the future.

Effect of noisy stimulation on neurobiological sensitization systems and its role for normal and pathological physiology

NASA Astrophysics Data System (ADS)

Huber, Martin; Braun, Hans; Krieg, J.\\:Urgen-Christian

2004-03-01

Sensitization is discussed as an important phenomenon playing a role in normal physiology but also with respect to the initiation and progression of a variety of neuropsychiatric disorders such as epilepsia, substance-related disorders or recurrent affective disorders. The relevance to understand the dynamics of sensitization phenomena is emphasized by recent findings that even single stimulations can induce longlasting changes in biological systems. To address specific questions associated with the sensitization dynamics, we use a computational approach and develop simple but physiologically-plausible models. In the present study we examine the effect of noisy stimulation on sensitization development in the model. We consider sub- and suprathresold stimulations with varying noise intensities and determine as response measures the (i) absolute number of stimulus-induced sensitzations and (ii) the temporal relsation of stimulus-sensitization coupling. The findings indicate that stochastic effects including stochastic resonance might well contribute to the physiology of sensitization mechanisms under both nomal and pathological conditions.

Host-regulated Hepatitis B Virus Capsid Assembly in a Mammalian Cell-free System.

PubMed

Liu, Kuancheng; Hu, Jianming

2018-04-20

The hepatitis B virus (HBV) is an important global human pathogen and represents a major cause of hepatitis, liver cirrhosis and liver cancer. The HBV capsid is composed of multiple copies of a single viral protein, the capsid or core protein (HBc), plays multiple roles in the viral life cycle, and has emerged recently as a major target for developing antiviral therapies against HBV infection. Although several systems have been developed to study HBV capsid assembly, including heterologous overexpression systems like bacteria and insect cells, in vitro assembly using purified protein, and mammalian cell culture systems, the requirement for non-physiological concentrations of HBc and salts and the difficulty in manipulating host regulators of assembly presents major limitations for detailed studies on capsid assembly under physiologically relevant conditions. We have recently developed a mammalian cell-free system based on the rabbit reticulocyte lysate (RRL), in which HBc is expressed at physiological concentrations and assembles into capsids under near-physiological conditions. This system has already revealed HBc assembly requirements that are not anticipated based on previous assembly systems. Furthermore, capsid assembly in this system is regulated by endogenous host factors that can be readily manipulated. Here we present a detailed protocol for this cell-free capsid assembly system, including an illustration on how to manipulate host factors that regulate assembly.

The stress response and immune system share, borrow, and reconfigure their physiological network elements: Evidence from the insects.

PubMed

Adamo, Shelley A

2017-02-01

The classic biomedical view is that stress hormone effects on the immune system are largely pathological, especially if the stress is chronic. However, more recent interpretations have focused on the potential adaptive function of these effects. This paper examines stress response-immune system interactions from a physiological network perspective, using insects because of their simpler physiology. For example, stress hormones can reduce disease resistance, yet activating an immune response results in the release of stress hormones in both vertebrates and invertebrates. From a network perspective, this phenomenon is consistent with the 'sharing' of the energy-releasing ability of stress hormones by both the stress response and the immune system. Stress-induced immunosuppression is consistent with the stress response 'borrowing' molecular components from the immune system to increase the capacity of stress-relevant physiological processes (i.e. a trade off). The insect stress hormones octopamine and adipokinetic hormone can also 'reconfigure' the immune system to help compensate for the loss of some of the immune system's molecular resources (e.g. apolipophorin III). This view helps explain seemingly maladaptive interactions between the stress response and immune system. The adaptiveness of stress hormone effects on individual immune components may be apparent only from the perspective of the whole organism. These broad principles will apply to both vertebrates and invertebrates. Copyright © 2016 Elsevier Inc. All rights reserved.

Sex Differences in Androgen Regulation of Metabolism in Nonhuman Primates.

PubMed

True, Cadence; Abbott, David H; Roberts, Charles T; Varlamov, Oleg

2017-01-01

The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females. This review will also focus on the interaction between altered androgen levels and dietary restriction and excess, in particular the Western-style diet that underlies significant human pathophysiology.

SEX DIFFERENCES IN ANDROGEN REGULATION OF METABOLISM IN NONHUMAN PRIMATES

PubMed Central

True, Cadence; Abbott, David H.; Roberts, Charles T.; Varlamov, Oleg

2018-01-01

The in-depth characterization of sex differences relevant to human physiology requires the judicious use of a variety of animal models and human clinical data. Nonhuman primates (NHPs) represent an important experimental system that bridges rodent studies and clinical investigations. NHP studies have been especially useful in understanding the role of sex hormones in development and metabolism and also allow the elucidation of the effects of pertinent dietary influences on physiology pertinent to disease states such as obesity and diabetes. This chapter summarizes the current state of our understanding of androgen effects on male and female NHP metabolism relevant to hypogonadism in human males and polycystic ovary syndrome in human females, as well as the interaction between altered androgen levels and dietary restriction and excess, in particular the western-style diet that underlies significant human pathophysiology. PMID:29224110

Kernel-Based Relevance Analysis with Enhanced Interpretability for Detection of Brain Activity Patterns

PubMed Central

Alvarez-Meza, Andres M.; Orozco-Gutierrez, Alvaro; Castellanos-Dominguez, German

2017-01-01

We introduce Enhanced Kernel-based Relevance Analysis (EKRA) that aims to support the automatic identification of brain activity patterns using electroencephalographic recordings. EKRA is a data-driven strategy that incorporates two kernel functions to take advantage of the available joint information, associating neural responses to a given stimulus condition. Regarding this, a Centered Kernel Alignment functional is adjusted to learning the linear projection that best discriminates the input feature set, optimizing the required free parameters automatically. Our approach is carried out in two scenarios: (i) feature selection by computing a relevance vector from extracted neural features to facilitating the physiological interpretation of a given brain activity task, and (ii) enhanced feature selection to perform an additional transformation of relevant features aiming to improve the overall identification accuracy. Accordingly, we provide an alternative feature relevance analysis strategy that allows improving the system performance while favoring the data interpretability. For the validation purpose, EKRA is tested in two well-known tasks of brain activity: motor imagery discrimination and epileptic seizure detection. The obtained results show that the EKRA approach estimates a relevant representation space extracted from the provided supervised information, emphasizing the salient input features. As a result, our proposal outperforms the state-of-the-art methods regarding brain activity discrimination accuracy with the benefit of enhanced physiological interpretation about the task at hand. PMID:29056897

Development of physiologically based toxicokinetic (PBTK) models for fish: Confessions of a former fish physiologist

EPA Science Inventory

Abstract: In toxicology, as in pharmacology, the fundamental paradigm used to describe chemical interactions with biological systems is the dose-response relationship. Depending on the chemical mode of action, however, the relevant expression of dose may any one of several metri...

Microbial ecology and host-microbiota interactions during early life stages

PubMed Central

Collado, Maria Carmen; Cernada, Maria; Baüerl, Christine; Vento, Máximo; Pérez-Martínez, Gaspar

2012-01-01

The role of human microbiota has been redefined during recent years and its physiological role is now much more important than earlier understood. Intestinal microbial colonization is essential for the maturation of immune system and for the developmental regulation of the intestinal physiology. Alterations in this process of colonization have been shown to predispose and increase the risk to disease later in life. The first contact of neonates with microbes is provided by the maternal microbiota. Moreover, mode of delivery, type of infant feeding and other perinatal factors can influence the establishment of the infant microbiota. Taken into consideration all the available information it could be concluded that the exposure to the adequate microbes early in gestation and neonatal period seems to have a relevant role in health. Maternal microbial environment affects maternal and fetal immune physiology and, of relevance, this interaction with microbes at the fetal-maternal interface could be modulated by specific microbes administered to the pregnant mother. Indeed, probiotic interventions aiming to reduce the risk of immune-mediated diseases may appear effective during early life. PMID:22743759

Ambulatory instrumentation suitable for long-term monitoring of cattle health.

PubMed

Schoenig, S A; Hildreth, T S; Nagl, L; Erickson, H; Spire, M; Andresen, D; Warren, S

2004-01-01

The benefits of real-time health diagnoses of cattle are potentially tremendous. Early detection of transmissible disease, whether from natural or terrorist events, could help to avoid huge financial losses in the agriculture industry while also improving meat quality. This work discusses physiological and behavioral parameters relevant to cattle state-of-health assessment. These parameters, along with a potentially harsh monitoring environment, drive a set of design considerations that must be addressed when building systems to acquire long-term, real-time measurements in the field. A prototype system is presented that supports the measurement of suitable physiologic parameters and begins to address the design constraints for continuous state-of-health determination in free-roaming cattle.

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

De Vos, Winnok H., E-mail: winnok.devos@uantwerpen.be; Cell Systems and Imaging Research Group, Department of Molecular Biotechnology, Ghent University, Ghent; Beghuin, Didier

As commercial space flights have become feasible and long-term extraterrestrial missions are planned, it is imperative that the impact of space travel and the space environment on human physiology be thoroughly characterized. Scrutinizing the effects of potentially detrimental factors such as ionizing radiation and microgravity at the cellular and tissue level demands adequate visualization technology. Advanced light microscopy (ALM) is the leading tool for non-destructive structural and functional investigation of static as well as dynamic biological systems. In recent years, technological developments and advances in photochemistry and genetic engineering have boosted all aspects of resolution, readout and throughput, rendering ALMmore » ideally suited for biological space research. While various microscopy-based studies have addressed cellular response to space-related environmental stressors, biological endpoints have typically been determined only after the mission, leaving an experimental gap that is prone to bias results. An on-board, real-time microscopical monitoring device can bridge this gap. Breadboards and even fully operational microscope setups have been conceived, but they need to be rendered more compact and versatile. Most importantly, they must allow addressing the impact of gravity, or the lack thereof, on physiologically relevant biological systems in space and in ground-based simulations. In order to delineate the essential functionalities for such a system, we have reviewed the pending questions in space science, the relevant biological model systems, and the state-of-the art in ALM. Based on a rigorous trade-off, in which we recognize the relevance of multi-cellular systems and the cellular microenvironment, we propose a compact, but flexible concept for space-related cell biological research that is based on light sheet microscopy.« less

Four-Channel Biosignal Analysis and Feature Extraction for Automatic Emotion Recognition

NASA Astrophysics Data System (ADS)

Kim, Jonghwa; André, Elisabeth

This paper investigates the potential of physiological signals as a reliable channel for automatic recognition of user's emotial state. For the emotion recognition, little attention has been paid so far to physiological signals compared to audio-visual emotion channels such as facial expression or speech. All essential stages of automatic recognition system using biosignals are discussed, from recording physiological dataset up to feature-based multiclass classification. Four-channel biosensors are used to measure electromyogram, electrocardiogram, skin conductivity and respiration changes. A wide range of physiological features from various analysis domains, including time/frequency, entropy, geometric analysis, subband spectra, multiscale entropy, etc., is proposed in order to search the best emotion-relevant features and to correlate them with emotional states. The best features extracted are specified in detail and their effectiveness is proven by emotion recognition results.

Evidence against Resveratrol as a viable therapy for the rescue of defective ΔF508 CFTR

PubMed Central

Jai, Ying; Shah, Kalpit; Bridges, Robert J.; Bradbury, Neil A.

2015-01-01

BACKGROUND Resveratrol, a natural phenolic compound, has been reported to rescue mutant ΔF508 CFTR in expression systems and primary epithelial cells. Although this implies a therapeutic benefit to patients with CF, investigations were performed using resveratrol concentrations greatly in excess of those achievable in plasma. We evaluated the efficacy of resveratrol as a CFTR corrector in relevant primary airway cells, using physiologically achievable resveratrol concentrations. METHODS Cells expressing wt or ΔF508 CFTR were exposed to chronic or acute resveratrol. CFTR mRNA and protein expression were monitored. The effects of resveratrol on primary ΔF508 human airway cells were evaluated by equivalent current analysis using modified Ussing chambers. RESULTS Consistent with previously published data in heterologous expression systems, high doses of resveratrol increased CFTR expression; however physiologically relevant concentrations were without effect. In contrast to heterologous expression systems, resveratrol was unable to increase mutant CFTR channel activity in primary airway cells. Elevated amiloride-sensitive currents, indicative of sodium transport and characteristically elevated in CF airway cells, were also unaffected by resveratrol CONCLUSIONS High concentrations of resveratrol can increase CFTR mRNA and protein in some cell types. In addition, acute resveratrol exposure can stimulate CFTR mediated chloride secretion, probably by increasing cellular cAMP levels. Resveratrol at physiologically achievable levels yielded no benefit in primary ΔF508 airway cells, either in terms of amiloride-sensitive currents of CFTR currents. PMID:26342647

The relationship between immediate relevant basic science knowledge and clinical knowledge: physiology knowledge and transthoracic echocardiography image interpretation.

PubMed

Nielsen, Dorte Guldbrand; Gotzsche, Ole; Sonne, Ole; Eika, Berit

2012-10-01

Two major views on the relationship between basic science knowledge and clinical knowledge stand out; the Two-world view seeing basic science and clinical science as two separate knowledge bases and the encapsulated knowledge view stating that basic science knowledge plays an overt role being encapsulated in the clinical knowledge. However, resent research has implied that a more complex relationship between the two knowledge bases exists. In this study, we explore the relationship between immediate relevant basic science (physiology) and clinical knowledge within a specific domain of medicine (echocardiography). Twenty eight medical students in their 3rd year and 45 physicians (15 interns, 15 cardiology residents and 15 cardiology consultants) took a multiple-choice test of physiology knowledge. The physicians also viewed images of a transthoracic echocardiography (TTE) examination and completed a checklist of possible pathologies found. A total score for each participant was calculated for the physiology test, and for all physicians also for the TTE checklist. Consultants scored significantly higher on the physiology test than did medical students and interns. A significant correlation between physiology test scores and TTE checklist scores was found for the cardiology residents only. Basic science knowledge of immediate relevance for daily clinical work expands with increased work experience within a specific domain. Consultants showed no relationship between physiology knowledge and TTE interpretation indicating that experts do not use basic science knowledge in routine daily practice, but knowledge of immediate relevance remains ready for use.

Performance of first-year health sciences students in a large, diverse, multidisciplinary, first-semester, physiology service module.

PubMed

Higgins-Opitz, Susan B; Tufts, Mark

2014-06-01

Health Science students at the University of KwaZulu-Natal perform better in their professional modules compared with their physiology modules. The pass rates of physiology service modules have steadily declined over the years. While a system is in place to identify "at-risk" students, it is only activated after the first semester. As a result, it is only from the second semester of their first year studies onward that at-risk students can be formally assisted. The challenge is thus to devise an appropriate strategy to identify struggling students earlier in the semester. Using questionnaires, students were asked about attendance, financing of their studies, and relevance of physiology. After the first class test, failing students were invited to complete a second questionnaire. In addition, demographic data were also collected and analyzed. Correlation analyses were undertaken of performance indicators based on the demographical data collected. The 2011 class comprised mainly sport science students (57%). The pass rate of sport science students was lower than the pass rates of other students (42% vs. 70%, P < 0.001). Most students were positive about physiology and recognized its relevance. Key issues identified were problems understanding concepts and terminology, poor study environment and skills, and lack of matriculation biology. The results of the first class test and final module marks correlated well. It is clear from this study that student performance in the first class test is a valuable tool to identify struggling students and that appropriate testing should be held as early as possible. Copyright © 2014 The American Physiological Society.

Study of electromechanical and mechanical properties of bacteria using force microscopy

NASA Astrophysics Data System (ADS)

Reukov, Vladimir; Thompson, Gary; Nikiforov, Maxim; Guo, Senli; Ovchinnikov, Oleg; Jesse, Stephen; Kalinin, Sergei; Vertegel, Alexey

2010-03-01

The application of scanning probe microscopy (SPM) to biological systems has evolved over the past decade into a multimodal and spectroscopic instrument that provides multiple information channels at each spatial pixel acquired. Recently, functional recognition imaging based on differing electromechanical properties between Gram negative and Gram positive bacteria was achieved using artificial neural network analysis of band excitation piezoresponse force microscopy (BEPFM) data. The immediate goal of this project was to study mechanical and electromechanical properties of bacterial systems physiologically-relevant solutions using Band-width Excitation Piezoresponce Force Microscopy (BE PFM) in combination with Force Mapping. Electromechanical imaging in physiological environments will improve the versatility of functional recognition imaging and open the way for application of the rapid BEPFM line mode method to other living cell systems.

The Use of Silk as a Scaffold for Mature, Sustainable Unilocular Adipose 3D Tissue Engineered Systems.

PubMed

Abbott, Rosalyn D; Wang, Rebecca Y; Reagan, Michaela R; Chen, Ying; Borowsky, Francis E; Zieba, Adam; Marra, Kacey G; Rubin, J Peter; Ghobrial, Irene M; Kaplan, David L

2016-07-01

There is a critical need for monitoring physiologically relevant, sustainable, human adipose tissues in vitro to gain new insights into metabolic diseases. To support long-term culture, a 3D silk scaffold assisted culture system is developed that maintains mature unilocular adipocytes ex vivo in coculture with preadipocytes, endothelial cells, and smooth muscle cells obtained from small volumes of liquefied adipose samples. Without the silk scaffold, adipose tissue explants cannot be sustained in long-term culture (3 months) due to their fragility. Adjustments to media components are used to tune lipid metabolism and proliferation, in addition to responsiveness to an inflammatory stimulus. Interestingly, patient specific responses to TNFα stimulation are observed, providing a proof-of-concept translational technique for patient specific disease modeling in the future. In summary, this novel 3D scaffold assisted approach is required for establishing physiologically relevant, sustainable, human adipose tissue systems from small volumes of lipoaspirate, making this methodology of great value to studies of metabolism, adipokine-driven diseases, and other diseases where the roles of adipocytes are only now becoming uncovered. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Knowledge Retention of Exercise Physiology Content between Athletes and Nonathletes

ERIC Educational Resources Information Center

Clark, Brian; Webster, Collin; Druger, Marvin

2006-01-01

Based on the idea that learning is linked to personal relevance, this study examined knowledge retention of exercise physiology content between college athletes and nonathletes. No differences were observed between the groups. These findings have implications on understanding the relationship between personal relevance and memory. (Contains 1…

Impedance-based cellular assay technologies: recent advances, future promise.

PubMed

McGuinness, Ryan

2007-10-01

Cell-based assays are continuing to grow in importance in the drug discovery workflow. Their early introduction holds the promise of limiting attrition in the later, more costly phases of the process. This article reviews recent advances in the development of impedance technologies for label-free cell-based assays. These systems are capable of monitoring endogenous receptor activation, and thus generate more physiologically relevant measures of pharmacological endpoints. Primary cells can be investigated as well, thus producing disease relevant information. Label-free assays significantly decrease assay development efforts and avoid many complications inherent in recombinant readout systems. Impedance-based systems have great potential to advance the utility of cell-based assays as they are applied to drug discovery and pharmacology.

Biological role of bacterial inclusion bodies: a model for amyloid aggregation.

PubMed

García-Fruitós, Elena; Sabate, Raimon; de Groot, Natalia S; Villaverde, Antonio; Ventura, Salvador

2011-07-01

Inclusion bodies are insoluble protein aggregates usually found in recombinant bacteria when they are forced to produce heterologous protein species. These particles are formed by polypeptides that cross-interact through sterospecific contacts and that are steadily deposited in either the cell's cytoplasm or the periplasm. An important fraction of eukaryotic proteins form inclusion bodies in bacteria, which has posed major problems in the development of the biotechnology industry. Over the last decade, the fine dissection of the quality control system in bacteria and the recognition of the amyloid-like architecture of inclusion bodies have provided dramatic insights on the dynamic biology of these aggregates. We discuss here the relevant aspects, in the interface between cell physiology and structural biology, which make inclusion bodies unique models for the study of protein aggregation, amyloid formation and prion biology in a physiologically relevant background. © 2011 The Authors Journal compilation © 2011 FEBS.

Approach to Reptile Emergency Medicine.

PubMed

Long, Simon Y

2016-05-01

This article summarizes the physiology and anatomy of reptiles, highlighting points relevant for emergency room veterinarians. Other systems, such as the endocrine and immune systems, have not been covered. The many other aspects of reptile species variation are too numerous to be covered. This article provides an overview but encourages clinicians to seek additional species-specific information to better medically diagnose and treat their reptile patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating physiological regulation with stem cell and tissue homeostasis

PubMed Central

Nakada, Daisuke; Levi, Boaz P.; Morrison, Sean J.

2015-01-01

Summary Stem cells are uniquely able to self-renew, to undergo multilineage differentiation, and to persist throughout life in a number of tissues. Stem cells are regulated by a combination of shared and tissue-specific mechanisms and are distinguished from restricted progenitors by differences in transcriptional and epigenetic regulation. Emerging evidence suggests that other aspects of cellular physiology, including mitosis, signal transduction, and metabolic regulation also differ between stem cells and their progeny. These differences may allow stem cells to be regulated independently of differentiated cells in response to circadian rhythms, changes in metabolism, diet, exercise, mating, aging, infection, and disease. This allows stem cells to sustain homeostasis or to remodel relevant tissues in response to physiological change. Stem cells are therefore not only regulated by short-range signals that maintain homeostasis within their tissue of origin, but also by long-range signals that integrate stem cell function with systemic physiology. PMID:21609826

Learning about stress: neural, endocrine and behavioral adaptations.

PubMed

McCarty, Richard

2016-09-01

In this review, nonassociative learning is advanced as an organizing principle to draw together findings from both sympathetic-adrenal medullary and hypothalamic-pituitary-adrenocortical (HPA) axis responses to chronic intermittent exposure to a variety of stressors. Studies of habituation, facilitation and sensitization of stress effector systems are reviewed and linked to an animal's prior experience with a given stressor, the intensity of the stressor and the appraisal by the animal of its ability to mobilize physiological systems to adapt to the stressor. Brain pathways that regulate physiological and behavioral responses to stress are discussed, especially in light of their regulation of nonassociative processes in chronic intermittent stress. These findings may have special relevance to various psychiatric diseases, including depression and post-traumatic stress disorder (PTSD).

Building an experimental model of the human body with non-physiological parameters.

PubMed

Labuz, Joseph M; Moraes, Christopher; Mertz, David R; Leung, Brendan M; Takayama, Shuichi

2017-03-01

New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform - commonly called a 'human-on-a-chip (HOC)' - requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo -like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O 2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10 -6 ) microfluidic model of the human body.

Building an experimental model of the human body with non-physiological parameters

PubMed Central

Labuz, Joseph M.; Moraes, Christopher; Mertz, David R.; Leung, Brendan M.; Takayama, Shuichi

2017-01-01

New advances in engineering and biomedical technology have enabled recent efforts to capture essential aspects of human physiology in microscale, in-vitro systems. The application of these advances to experimentally model complex processes in an integrated platform — commonly called a ‘human-on-a-chip (HOC)’ — requires that relevant compartments and parameters be sized correctly relative to each other and to the system as a whole. Empirical observation, theoretical treatments of resource distribution systems and natural experiments can all be used to inform rational design of such a system, but technical and fundamental challenges (e.g. small system blood volumes and context-dependent cell metabolism, respectively) pose substantial, unaddressed obstacles. Here, we put forth two fundamental principles for HOC design: inducing in-vivo-like cellular metabolic rates is necessary and may be accomplished in-vitro by limiting O2 availability and that the effects of increased blood volumes on drug concentration can be mitigated through pharmacokinetics-based treatments of solute distribution. Combining these principles with natural observation and engineering workarounds, we derive a complete set of design criteria for a practically realizable, physiologically faithful, five-organ millionth-scale (× 10−6) microfluidic model of the human body. PMID:28713851

Invited review article: Advanced light microscopy for biological space research.

PubMed

De Vos, Winnok H; Beghuin, Didier; Schwarz, Christian J; Jones, David B; van Loon, Jack J W A; Bereiter-Hahn, Juergen; Stelzer, Ernst H K

2014-10-01

As commercial space flights have become feasible and long-term extraterrestrial missions are planned, it is imperative that the impact of space travel and the space environment on human physiology be thoroughly characterized. Scrutinizing the effects of potentially detrimental factors such as ionizing radiation and microgravity at the cellular and tissue level demands adequate visualization technology. Advanced light microscopy (ALM) is the leading tool for non-destructive structural and functional investigation of static as well as dynamic biological systems. In recent years, technological developments and advances in photochemistry and genetic engineering have boosted all aspects of resolution, readout and throughput, rendering ALM ideally suited for biological space research. While various microscopy-based studies have addressed cellular response to space-related environmental stressors, biological endpoints have typically been determined only after the mission, leaving an experimental gap that is prone to bias results. An on-board, real-time microscopical monitoring device can bridge this gap. Breadboards and even fully operational microscope setups have been conceived, but they need to be rendered more compact and versatile. Most importantly, they must allow addressing the impact of gravity, or the lack thereof, on physiologically relevant biological systems in space and in ground-based simulations. In order to delineate the essential functionalities for such a system, we have reviewed the pending questions in space science, the relevant biological model systems, and the state-of-the art in ALM. Based on a rigorous trade-off, in which we recognize the relevance of multi-cellular systems and the cellular microenvironment, we propose a compact, but flexible concept for space-related cell biological research that is based on light sheet microscopy.

Invited Review Article: Advanced light microscopy for biological space research

NASA Astrophysics Data System (ADS)

De Vos, Winnok H.; Beghuin, Didier; Schwarz, Christian J.; Jones, David B.; van Loon, Jack J. W. A.; Bereiter-Hahn, Juergen; Stelzer, Ernst H. K.

2014-10-01

As commercial space flights have become feasible and long-term extraterrestrial missions are planned, it is imperative that the impact of space travel and the space environment on human physiology be thoroughly characterized. Scrutinizing the effects of potentially detrimental factors such as ionizing radiation and microgravity at the cellular and tissue level demands adequate visualization technology. Advanced light microscopy (ALM) is the leading tool for non-destructive structural and functional investigation of static as well as dynamic biological systems. In recent years, technological developments and advances in photochemistry and genetic engineering have boosted all aspects of resolution, readout and throughput, rendering ALM ideally suited for biological space research. While various microscopy-based studies have addressed cellular response to space-related environmental stressors, biological endpoints have typically been determined only after the mission, leaving an experimental gap that is prone to bias results. An on-board, real-time microscopical monitoring device can bridge this gap. Breadboards and even fully operational microscope setups have been conceived, but they need to be rendered more compact and versatile. Most importantly, they must allow addressing the impact of gravity, or the lack thereof, on physiologically relevant biological systems in space and in ground-based simulations. In order to delineate the essential functionalities for such a system, we have reviewed the pending questions in space science, the relevant biological model systems, and the state-of-the art in ALM. Based on a rigorous trade-off, in which we recognize the relevance of multi-cellular systems and the cellular microenvironment, we propose a compact, but flexible concept for space-related cell biological research that is based on light sheet microscopy.

We can't explore space without it - Common human space needs for exploration spaceflight

NASA Technical Reports Server (NTRS)

Daues, K. R.; Erwin, H. O.

1992-01-01

An overview is conducted of physiological, psychological, and human-interface requirements for manned spaceflight programs to establish common criteria. Attention is given to the comfort levels relevant to human support in exploration mission spacecraft and planetary habitats, and three comfort levels (CLs) are established. The levels include: (1) CL-1 for basic crew life support; (2) CL-2 for enabling the nominal completion of mission science; and (3) CL-3 which provides for enhanced life support and user-friendly interface systems. CL-2 support systems can include systems for EVA, workstations, and activity centers for repairs and enhanced utilization of payload and human/machine integration. CL-3 supports can be useful for maintaining crew psychological and physiological health as well as the design of comfortable and earthlike surroundings. While all missions require CL-1 commonality, CL-2 commonality is required only for EVA systems, display nomenclature, and restraint designs.

Comparisons between the attitudes of medical and dental students toward the clinical importance of gross anatomy and physiology.

PubMed

Olowo-Ofayoku, Anthony; Moxham, Bernard John

2014-10-01

Marked changes are occurring within both the medical and dental curricula and new ways of teaching the basic sciences have been devised and traditional methods (e.g., dissection for gross anatomy and of bench-based animal preparations for physiology) are increasingly no longer the norm. Although there is much anecdotal evidence that students are not in favor of such changes, there is little evidence for this based on quantitative analyses of students' attitudes. Using Thurstone and Chave attitude analyses, we assessed the attitudes of first year medical and dental students at Cardiff University toward gross anatomy and physiology in terms of their perceived clinical importance. In addition, we investigated the appropriateness ("fitness for purpose") of teaching methodologies used for anatomy and physiology. The hypotheses tested recognized the possibility that medical and dental students differed in their opinions, but that they had a preference to being taught gross anatomy through the use of dissection and had no preference for physiology teaching. It was found that both medical and dental students displayed positive attitudes toward the clinical relevance of gross anatomy and that they preferred to be taught by means of dissection. Although both medical and dental students displayed positives attitudes toward the clinical relevance of physiology, this was greater for the medical students. Both medical and dental students showed a preference for being taught physiology through didactic teaching in small groups but the medical students also appreciated being taught by means of practicals. Overall, this study highlights the expectations that students have for the basic science foundation teaching within their professional training and signals a preference for being taught experientially/practically. Differences were discerned between medical and dental students that might reflect the direct association between systems physiology and pathophysiology and the application of this knowledge within the medical field in comparison to the dental field, which is heavily skill-based. © 2014 Wiley Periodicals, Inc.

An Update on Non-CB1, Non-CB2 Cannabinoid Related G-Protein-Coupled Receptors

PubMed Central

Morales, Paula; Reggio, Patricia H.

2017-01-01

Abstract The endocannabinoid system (ECS) has been shown to be of great importance in the regulation of numerous physiological and pathological processes. To date, two Class A G-protein-coupled receptors (GPCRs) have been discovered and validated as the main therapeutic targets of this system: the cannabinoid receptor type 1 (CB1), which is the most abundant neuromodulatory receptor in the brain, and the cannabinoid receptor type 2 (CB2), predominantly found in the immune system among other organs and tissues. Endogenous cannabinoid receptor ligands (endocannabinoids) and the enzymes involved in their synthesis, cell uptake, and degradation have also been identified as part of the ECS. However, its complex pharmacology suggests that other GPCRs may also play physiologically relevant roles in this therapeutically promising system. In the last years, GPCRs such as GPR18 and GPR55 have emerged as possible missing members of the cannabinoid family. This categorization still stimulates strong debate due to the lack of pharmacological tools to validate it. Because of their close phylogenetic relationship, the Class A orphan GPCRs, GPR3, GPR6, and GPR12, have also been associated with the cannabinoids. Moreover, certain endo-, phyto-, and synthetic cannabinoid ligands have displayed activity at other well-established GPCRs, including the opioid, adenosine, serotonin, and dopamine receptor families. In addition, the cannabinoid receptors have also been shown to form dimers with other GPCRs triggering cross-talk signaling under specific conditions. In this mini review, we aim to provide insight into the non-CB1, non-CB2 cannabinoid-related GPCRs that have been reported thus far. We consider the physiological relevance of these molecular targets in modulating the ECS. PMID:29098189

Causes of Low and High Citation Potentials in Science: Citation Analysis of Biochemistry and Plant Physiology Journals.

ERIC Educational Resources Information Center

Marton, Janos

1983-01-01

Citation data of 16 biochemistry and plant physiology journals show that reasons for lower citation potentials of plant physiology articles are: (1) readership is narrower for plant physiology journals; (2) plant physiologists can cite fewer thematically relevant new articles; and (3) plant physiology research fields are more isolated. References…

The Neuroendocrinology of the Microbiota-Gut-Brain Axis: A Behavioural Perspective.

PubMed

Cussotto, Sofia; Sandhu, Kiran V; Dinan, Timothy G; Cryan, John F

2018-05-10

The human gut harbours trillions of symbiotic bacteria that play a key role in programming different aspects of host physiology in health and disease. These intestinal microbes are also key components of the gut-brain axis, the bidirectional communication pathway between the gut and the central nervous system (CNS). In addition, the CNS is closely interconnected with the endocrine system to regulate many physiological processes. An expanding body of evidence is supporting the notion that gut microbiota modifications and/or manipulations may also play a crucial role in the manifestation of specific behavioural responses regulated by neuroendocrine pathways. In this review, we will focus on how the intestinal microorganisms interact with elements of the host neuroendocrine system to modify behaviours relevant to stress, eating behaviour, sexual behaviour, social behaviour, cognition and addiction. Copyright © 2018. Published by Elsevier Inc.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

PubMed

Ardell, J L; Andresen, M C; Armour, J A; Billman, G E; Chen, P-S; Foreman, R D; Herring, N; O'Leary, D S; Sabbah, H N; Schultz, H D; Sunagawa, K; Zucker, I H

2016-07-15

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Monochloramine Cometabolism by Nitrifying Biofilm Relevant ...

EPA Pesticide Factsheets

Recently, biological monochloramine removal (i.e., cometabolism) by a pure culture ammonia–oxidizing bacteria, Nitrosomonas europaea, and a nitrifying mixed–culture have been shown to increase monochloramine demand. Although important, these previous suspended culture batch kinetic experiments were not representative of drinking water distribution systems where bacteria grow predominantly as biofilm attached to pipe walls or sediments and physiological differences may exist between suspension and biofilm growth. Therefore, the current research was an important next step in extending the previous results to investigate monochloramine cometabolism by biofilm grown in annular reactors under drinking water relevant conditions. Estimated monochloramine cometabolism kinetics were similar to those of ammonia metabolism, and monochloramine cometabolism was a significant loss mechanism (25–40% of the observed monochloramine loss). These results demonstrated that monochloramine cometabolism occurred in drinking water relevant nitrifying biofilm; thus, cometabolism may be a significant contribution to monochloramine loss during nitrification episodes in distribution systems. Investigate whether or not nitrifying biofilm can biologically transform monochloramine under drinking water relevant conditions.

On the analysis of complex biological supply chains: From Process Systems Engineering to Quantitative Systems Pharmacology.

PubMed

Rao, Rohit T; Scherholz, Megerle L; Hartmanshenn, Clara; Bae, Seul-A; Androulakis, Ioannis P

2017-12-05

The use of models in biology has become particularly relevant as it enables investigators to develop a mechanistic framework for understanding the operating principles of living systems as well as in quantitatively predicting their response to both pathological perturbations and pharmacological interventions. This application has resulted in a synergistic convergence of systems biology and pharmacokinetic-pharmacodynamic modeling techniques that has led to the emergence of quantitative systems pharmacology (QSP). In this review, we discuss how the foundational principles of chemical process systems engineering inform the progressive development of more physiologically-based systems biology models.

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

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

Ucciferri, Nadia; Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa; Sbrana, Tommaso

2014-12-17

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting differentmore » cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.« less

Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism.

PubMed

Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

2014-01-01

Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

Guiding the osteogenic fate of mouse and human mesenchymal stem cells through feedback system control.

PubMed

Honda, Yoshitomo; Ding, Xianting; Mussano, Federico; Wiberg, Akira; Ho, Chih-Ming; Nishimura, Ichiro

2013-12-05

Stem cell-based disease modeling presents unique opportunities for mechanistic elucidation and therapeutic targeting. The stable induction of fate-specific differentiation is an essential prerequisite for stem cell-based strategy. Bone morphogenetic protein 2 (BMP-2) initiates receptor-regulated Smad phosphorylation, leading to the osteogenic differentiation of mesenchymal stromal/stem cells (MSC) in vitro; however, it requires supra-physiological concentrations, presenting a bottleneck problem for large-scale drug screening. Here, we report the use of a double-objective feedback system control (FSC) with a differential evolution (DE) algorithm to identify osteogenic cocktails of extrinsic factors. Cocktails containing significantly reduced doses of BMP-2 in combination with physiologically relevant doses of dexamethasone, ascorbic acid, beta-glycerophosphate, heparin, retinoic acid and vitamin D achieved accelerated in vitro mineralization of mouse and human MSC. These results provide insight into constructive approaches of FSC to determine the applicable functional and physiological environment for MSC in disease modeling, drug screening and tissue engineering.

Redox Regulation of Endothelial Cell Fate

PubMed Central

Song, Ping; Zou, Ming-Hui

2014-01-01

Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

Guiding the osteogenic fate of mouse and human mesenchymal stem cells through feedback system control

PubMed Central

Honda, Yoshitomo; Ding, Xianting; Mussano, Federico; Wiberg, Akira; Ho, Chih-ming; Nishimura, Ichiro

2013-01-01

Stem cell-based disease modeling presents unique opportunities for mechanistic elucidation and therapeutic targeting. The stable induction of fate-specific differentiation is an essential prerequisite for stem cell-based strategy. Bone morphogenetic protein 2 (BMP-2) initiates receptor-regulated Smad phosphorylation, leading to the osteogenic differentiation of mesenchymal stromal/stem cells (MSC) in vitro; however, it requires supra-physiological concentrations, presenting a bottleneck problem for large-scale drug screening. Here, we report the use of a double-objective feedback system control (FSC) with a differential evolution (DE) algorithm to identify osteogenic cocktails of extrinsic factors. Cocktails containing significantly reduced doses of BMP-2 in combination with physiologically relevant doses of dexamethasone, ascorbic acid, beta-glycerophosphate, heparin, retinoic acid and vitamin D achieved accelerated in vitro mineralization of mouse and human MSC. These results provide insight into constructive approaches of FSC to determine the applicable functional and physiological environment for MSC in disease modeling, drug screening and tissue engineering. PMID:24305548

Physiological sensor signals classification for healthcare using sensor data fusion and case-based reasoning.

PubMed

Begum, Shahina; Barua, Shaibal; Ahmed, Mobyen Uddin

2014-07-03

Today, clinicians often do diagnosis and classification of diseases based on information collected from several physiological sensor signals. However, sensor signal could easily be vulnerable to uncertain noises or interferences and due to large individual variations sensitivity to different physiological sensors could also vary. Therefore, multiple sensor signal fusion is valuable to provide more robust and reliable decision. This paper demonstrates a physiological sensor signal classification approach using sensor signal fusion and case-based reasoning. The proposed approach has been evaluated to classify Stressed or Relaxed individuals using sensor data fusion. Physiological sensor signals i.e., Heart Rate (HR), Finger Temperature (FT), Respiration Rate (RR), Carbon dioxide (CO2) and Oxygen Saturation (SpO2) are collected during the data collection phase. Here, sensor fusion has been done in two different ways: (i) decision-level fusion using features extracted through traditional approaches; and (ii) data-level fusion using features extracted by means of Multivariate Multiscale Entropy (MMSE). Case-Based Reasoning (CBR) is applied for the classification of the signals. The experimental result shows that the proposed system could classify Stressed or Relaxed individual 87.5% accurately compare to an expert in the domain. So, it shows promising result in the psychophysiological domain and could be possible to adapt this approach to other relevant healthcare systems.

How to apply clinical cases and medical literature in the framework of a modified "failure mode and effects analysis" as a clinical reasoning tool--an illustration using the human biliary system.

PubMed

Wong, Kam Cheong

2016-04-06

Clinicians use various clinical reasoning tools such as Ishikawa diagram to enhance their clinical experience and reasoning skills. Failure mode and effects analysis, which is an engineering methodology in origin, can be modified and applied to provide inputs into an Ishikawa diagram. The human biliary system is used to illustrate a modified failure mode and effects analysis. The anatomical and physiological processes of the biliary system are reviewed. Failure is defined as an abnormality caused by infective, inflammatory, obstructive, malignancy, autoimmune and other pathological processes. The potential failures, their effect(s), main clinical features, and investigation that can help a clinician to diagnose at each anatomical part and physiological process are reviewed and documented in a modified failure mode and effects analysis table. Relevant medical and surgical cases are retrieved from the medical literature and weaved into the table. A total of 80 clinical cases which are relevant to the modified failure mode and effects analysis for the human biliary system have been reviewed and weaved into a designated table. The table is the backbone and framework for further expansion. Reviewing and updating the table is an iterative and continual process. The relevant clinical features in the modified failure mode and effects analysis are then extracted and included in the relevant Ishikawa diagram. This article illustrates an application of engineering methodology in medicine, and it sows the seeds of potential cross-pollination between engineering and medicine. Establishing a modified failure mode and effects analysis can be a teamwork project or self-directed learning process, or a mix of both. Modified failure mode and effects analysis can be deployed to obtain inputs for an Ishikawa diagram which in turn can be used to enhance clinical experiences and clinical reasoning skills for clinicians, medical educators, and students.

What makes the learning of physiology in a PBL medical curriculum challenging? Student perceptions.

PubMed

Tufts, Mark A; Higgins-Opitz, Susan B

2009-09-01

Physiology is an integral component of any medical curriculum. Traditionally, the learning of physiology has relied heavily on systems-based didactic lectures. In 2001, the Nelson R. Mandela School of Medicine (NRMSM; Durban, South Africa) embarked on a problem-based curriculum in which the learning of physiology was integrated with relevant clinical scenarios. Students are expected to gain an understanding of physiology through self-directed research with only certain aspects being covered in large-group resource sessions (LGRSs). It has gradually become evident that this approach has resulted in significant gaps in students' understanding of basic physiological concepts. A survey of student perceptions of needs for physiology was undertaken to gain a better understanding of their perceived problems and also to inform them of proposed curricular changes. Students were asked to what extent they thought physiology was essential for their understanding of pathology, interpretation of patients' clinical signs and presentation of symptoms, and analysis of laboratory results. Students were also invited to detail the difficulties they experienced in understanding in LGRSs on clinical and physiological topics. The results of the survey indicate that greater interaction of students with experts is needed. In particular, students felt that they lacked the basic conceptual foundations essential for the learning and understanding of physiology, since the difficulties that the students identified are mainly terminological and conceptual in nature.

Performance of first-year health sciences students in a large, diverse, multidisciplinary, first-semester, physiology service module

PubMed Central

Tufts, Mark

2014-01-01

Health Science students at the University of KwaZulu-Natal perform better in their professional modules compared with their physiology modules. The pass rates of physiology service modules have steadily declined over the years. While a system is in place to identify “at-risk” students, it is only activated after the first semester. As a result, it is only from the second semester of their first year studies onward that at-risk students can be formally assisted. The challenge is thus to devise an appropriate strategy to identify struggling students earlier in the semester. Using questionnaires, students were asked about attendance, financing of their studies, and relevance of physiology. After the first class test, failing students were invited to complete a second questionnaire. In addition, demographic data were also collected and analyzed. Correlation analyses were undertaken of performance indicators based on the demographical data collected. The 2011 class comprised mainly sport science students (57%). The pass rate of sport science students was lower than the pass rates of other students (42% vs. 70%, P < 0.001). Most students were positive about physiology and recognized its relevance. Key issues identified were problems understanding concepts and terminology, poor study environment and skills, and lack of matriculation biology. The results of the first class test and final module marks correlated well. It is clear from this study that student performance in the first class test is a valuable tool to identify struggling students and that appropriate testing should be held as early as possible. PMID:24913452

Automated patch clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction.

PubMed

Stoelzle, Sonja; Haythornthwaite, Alison; Kettenhofen, Ralf; Kolossov, Eugen; Bohlen, Heribert; George, Michael; Brüggemann, Andrea; Fertig, Niels

2011-09-01

Cardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. Similar to primary cells, in vitro-generated stem cell-derived cardiomyocytes simultaneously express cardiac ion channels. Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. The aim of this study was to determine if stem cell-derived cardiomyocytes are suited for use in an automated patch clamp system. The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell-derived cardiomyocytes. Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system.

Creating Simulated Microgravity Patient Models

NASA Technical Reports Server (NTRS)

Hurst, Victor; Doerr, Harold K.; Bacal, Kira

2004-01-01

The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

In-cell thermodynamics and a new role for protein surfaces.

PubMed

Smith, Austin E; Zhou, Larry Z; Gorensek, Annelise H; Senske, Michael; Pielak, Gary J

2016-02-16

There is abundant, physiologically relevant knowledge about protein cores; they are hydrophobic, exquisitely well packed, and nearly all hydrogen bonds are satisfied. An equivalent understanding of protein surfaces has remained elusive because proteins are almost exclusively studied in vitro in simple aqueous solutions. Here, we establish the essential physiological roles played by protein surfaces by measuring the equilibrium thermodynamics and kinetics of protein folding in the complex environment of living Escherichia coli cells, and under physiologically relevant in vitro conditions. Fluorine NMR data on the 7-kDa globular N-terminal SH3 domain of Drosophila signal transduction protein drk (SH3) show that charge-charge interactions are fundamental to protein stability and folding kinetics in cells. Our results contradict predictions from accepted theories of macromolecular crowding and show that cosolutes commonly used to mimic the cellular interior do not yield physiologically relevant information. As such, we provide the foundation for a complete picture of protein chemistry in cells.

Comparative and integrative metabolomics reveal that S-nitrosation inhibits physiologically relevant metabolic enzymes.

PubMed

Bruegger, Joel J; Smith, Brian C; Wynia-Smith, Sarah L; Marletta, Michael A

2018-04-27

Cysteine S -nitrosation is a reversible post-translational modification mediated by nitric oxide ( • NO)-derived agents. S -Nitrosation participates in cellular signaling and is associated with several diseases such as cancer, cardiovascular diseases, and neuronal disorders. Despite the physiological importance of this nonclassical • NO-signaling pathway, little is understood about how much S -nitrosation affects protein function. Moreover, identifying physiologically relevant targets of S -nitrosation is difficult because of the dynamics of transnitrosation and a limited understanding of the physiological mechanisms leading to selective protein S -nitrosation. To identify proteins whose activities are modulated by S -nitrosation, we performed a metabolomics study comparing WT and endothelial nitric-oxide synthase knockout mice. We integrated our results with those of a previous proteomics study that identified physiologically relevant S -nitrosated cysteines, and we found that the activity of at least 21 metabolic enzymes might be regulated by S -nitrosation. We cloned, expressed, and purified four of these enzymes and observed that S -nitrosation inhibits the metabolic enzymes 6-phosphogluconate dehydrogenase, Δ1-pyrroline-5-carboxylate dehydrogenase, catechol- O -methyltransferase, and d-3-phosphoglycerate dehydrogenase. Furthermore, using site-directed mutagenesis, we identified the predominant cysteine residue influencing the observed activity changes in each enzyme. In summary, using an integrated metabolomics approach, we have identified several physiologically relevant S -nitrosation targets, including metabolic enzymes, which are inhibited by this modification, and we have found the cysteines modified by S -nitrosation in each enzyme. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

A G Protein-biased Designer G Protein-coupled Receptor Useful for Studying the Physiological Relevance of Gq/11-dependent Signaling Pathways.

PubMed

Hu, Jianxin; Stern, Matthew; Gimenez, Luis E; Wanka, Lizzy; Zhu, Lu; Rossi, Mario; Meister, Jaroslawna; Inoue, Asuka; Beck-Sickinger, Annette G; Gurevich, Vsevolod V; Wess, Jürgen

2016-04-08

Designerreceptorsexclusivelyactivated by adesignerdrug (DREADDs) are clozapine-N-oxide-sensitive designer G protein-coupled receptors (GPCRs) that have emerged as powerful novel chemogenetic tools to study the physiological relevance of GPCR signaling pathways in specific cell types or tissues. Like endogenous GPCRs, clozapine-N-oxide-activated DREADDs do not only activate heterotrimeric G proteins but can also trigger β-arrestin-dependent (G protein-independent) signaling. To dissect the relative physiological relevance of G protein-mediatedversusβ-arrestin-mediated signaling in different cell types or physiological processes, the availability of G protein- and β-arrestin-biased DREADDs would be highly desirable. In this study, we report the development of a mutationally modified version of a non-biased DREADD derived from the M3muscarinic receptor that can activate Gq/11with high efficacy but lacks the ability to interact with β-arrestins. We also demonstrate that this novel DREADD is activein vivoand that cell type-selective expression of this new designer receptor can provide novel insights into the physiological roles of G protein (Gq/11)-dependentversusβ-arrestin-dependent signaling in hepatocytes. Thus, this novel Gq/11-biased DREADD represents a powerful new tool to study the physiological relevance of Gq/11-dependent signaling in distinct tissues and cell types, in the absence of β-arrestin-mediated cellular effects. Such studies should guide the development of novel classes of functionally biased ligands that show high efficacy in various pathophysiological conditions but display a reduced incidence of side effects. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Spaceflight and Neurosurgery: A Comprehensive Review of the Relevant Literature.

PubMed

Swinney, Christian C; Allison, Zain

2018-01-01

Spaceflight and the associated gravitational fluctuations may impact various components of the central nervous system. These include changes in intracranial pressure, the spine, and neurocognitive performance. The implications of altered astronaut performance on critical spaceflight missions are potentially significant. The current body of research on this important topic is extremely limited, and a comprehensive review has not been published. Herein, the authors address this notable gap, as well as the role of the neurosurgeon in optimizing potential diagnostic and therapeutic modalities. A literature search was conducted using the PubMed, EMBASE, and Google Scholar databases, with no time constraints. Significant manuscripts on physiologic changes associated with spaceflight and microgravity were identified and reviewed. Manifestations were separated into 1 of 3 general categories, including changes in intracranial pressure, the spine, and neurocognitive performance. A comprehensive literature review yielded 27 studies with direct relevance to the impact of microgravity and spaceflight on nervous system physiology. This included 7 studies related to intracranial pressure fluctuations, 17 related to changes in the spinal column, and 3 related to neurocognitive change. The microgravity environment encountered during spaceflight impacts intracranial physiology. This includes changes in intracranial pressure, the spinal column, and neurocognitive performance. Herein, we present a systematic review of the published literature on this issue. Neurosurgeons should have a key role in the continued study of this important topic, contributing to both diagnostic and therapeutic understanding. Copyright © 2017 Elsevier Inc. All rights reserved.

Hydrogen sulphide in cardiovascular system: A cascade from interaction between sulphur atoms and signalling molecules.

PubMed

Wang, Ming-Jie; Cai, Wen-Jie; Zhu, Yi-Chun

2016-05-15

As a gasotransmitter, hydrogen sulphide exerts its extensive physiological and pathophysiological effects in mammals. The interaction between sulphur atoms and signalling molecules forms a cascade that modulates cellular functions and homeostasis. In this review, we focus on the signalling mechanism underlying the effect of hydrogen sulphide in the cardiovascular system and metabolism as well as the biological relevance to human diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Mining functionally relevant gene sets for analyzing physiologically novel clinical expression data.

PubMed

Turcan, Sevin; Vetter, Douglas E; Maron, Jill L; Wei, Xintao; Slonim, Donna K

2011-01-01

Gene set analyses have become a standard approach for increasing the sensitivity of transcriptomic studies. However, analytical methods incorporating gene sets require the availability of pre-defined gene sets relevant to the underlying physiology being studied. For novel physiological problems, relevant gene sets may be unavailable or existing gene set databases may bias the results towards only the best-studied of the relevant biological processes. We describe a successful attempt to mine novel functional gene sets for translational projects where the underlying physiology is not necessarily well characterized in existing annotation databases. We choose targeted training data from public expression data repositories and define new criteria for selecting biclusters to serve as candidate gene sets. Many of the discovered gene sets show little or no enrichment for informative Gene Ontology terms or other functional annotation. However, we observe that such gene sets show coherent differential expression in new clinical test data sets, even if derived from different species, tissues, and disease states. We demonstrate the efficacy of this method on a human metabolic data set, where we discover novel, uncharacterized gene sets that are diagnostic of diabetes, and on additional data sets related to neuronal processes and human development. Our results suggest that our approach may be an efficient way to generate a collection of gene sets relevant to the analysis of data for novel clinical applications where existing functional annotation is relatively incomplete.

Pharmacogenetics and forensic toxicology.

PubMed

Musshoff, Frank; Stamer, Ulrike M; Madea, Burkhard

2010-12-15

Large inter-individual variability in drug response and toxicity, as well as in drug concentrations after application of the same dosage, can be of genetic, physiological, pathophysiological, or environmental origin. Absorption, distribution and metabolism of a drug and interactions with its target often are determined by genetic differences. Pharmacokinetic and pharmacodynamic variations can appear at the level of drug metabolizing enzymes (e.g., the cytochrome P450 system), drug transporters, drug targets or other biomarker genes. Pharmacogenetics or toxicogenetics can therefore be relevant in forensic toxicology. This review presents relevant aspects together with some examples from daily routines. Copyright © 2010. Published by Elsevier Ireland Ltd.

Animal thermoregulation: a review of insulation, physiology and behaviour relevant to temperature control in buildings.

PubMed

McCafferty, D J; Pandraud, G; Gilles, J; Fabra-Puchol, M; Henry, P-Y

2017-12-28

Birds and mammals have evolved many thermal adaptations that are relevant to the bioinspired design of temperature control systems and energy management in buildings. Similar to many buildings, endothermic animals generate internal metabolic heat, are well insulated, regulate their temperature within set limits, modify microclimate and adjust thermal exchange with their environment. We review the major components of animal thermoregulation in endothermic birds and mammals that are pertinent to building engineering, in a world where climate is changing and reduction in energy use is needed. In animals, adjustment of insulation together with physiological and behavioural responses to changing environmental conditions fine-tune spatial and temporal regulation of body temperature, while also minimizing energy expenditure. These biological adaptations are characteristically flexible, allowing animals to alter their body temperatures to hourly, daily, or annual demands for energy. They exemplify how buildings could become more thermally reactive to meteorological fluctuations, capitalising on dynamic thermal materials and system properties. Based on this synthesis, we suggest that heat transfer modelling could be used to simulate these flexible biomimetic features and assess their success in reducing energy costs while maintaining thermal comfort for given building types.

Costs and benefits of sublethal Drosophila C virus infection.

PubMed

Gupta, V; Stewart, C O; Rund, S S C; Monteith, K; Vale, P F

2017-07-01

Viruses are major evolutionary drivers of insect immune systems. Much of our knowledge of insect immune responses derives from experimental infections using the fruit fly Drosophila melanogaster. Most experiments, however, employ lethal pathogen doses through septic injury, frequently overwhelming host physiology. While this approach has revealed several immune mechanisms, it is less informative about the fitness costs hosts may experience during infection in the wild. Using both systemic and oral infection routes, we find that even apparently benign, sublethal infections with the horizontally transmitted Drosophila C virus (DCV) can cause significant physiological and behavioural morbidity that is relevant for host fitness. We describe DCV-induced effects on fly reproductive output, digestive health and locomotor activity, and we find that viral morbidity varies according to the concentration of pathogen inoculum, host genetic background and sex. Notably, sublethal DCV infection resulted in a significant increase in fly reproduction, but this effect depended on host genotype. We discuss the relevance of sublethal morbidity for Drosophila ecology and evolution, and more broadly, we remark on the implications of deleterious and beneficial infections for the evolution of insect immunity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

Bioenergetics and synaptic plasticity as potential targets for individualizing treatment for depression.

PubMed

Price, J Blair; Bronars, Carrie; Erhardt, Sophie; Cullen, Kathyrn R; Schwieler, Lilly; Berk, Michael; Walder, Ken; McGee, Sean L; Frye, Mark A; Tye, Susannah J

2018-04-12

Disruptions of bioenergetic signaling and neurogenesis are hallmarks of depression physiology and are often the product of dysregulation of the inflammatory, stress-response, and metabolic systems. These systems are extensively interrelated at the physiological level, yet the bulk of the literature to date addresses pathophysiological mechanisms in isolation. A more integrated understanding of the etiology, progression, and treatment response profiles of depression is possible through wider consideration of relevant preclinical and clinical studies that examine the result of disruptions in these systems. Here, we review recent data demonstrating the critical effects of bioenergetic disruption on neuroplasticity and the development and progression of depressive illness. We further highlight the interactive and dynamic nature of the inflammatory and stress response systems and how disruption of these systems influences bioenergetic signaling pathways critical to treatment outcomes. In so doing, we underscore the pressing need to reconsider the implications of treatment resistance and present a framework for developing novel, personalized treatment approaches for depression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Is Ghrelin Synthesized in the Central Nervous System?

PubMed Central

Cabral, Agustina; López Soto, Eduardo J.; Epelbaum, Jacques; Perelló, Mario

2017-01-01

Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals. PMID:28294994

Is Ghrelin Synthesized in the Central Nervous System?

PubMed

Cabral, Agustina; López Soto, Eduardo J; Epelbaum, Jacques; Perelló, Mario

2017-03-15

Ghrelin is an octanoylated peptide that acts via its specific receptor, the growth hormone secretagogue receptor type 1a (GHSR-1a), and regulates a vast variety of physiological functions. It is well established that ghrelin is predominantly synthesized by a distinct population of endocrine cells located within the gastric oxyntic mucosa. In addition, some studies have reported that ghrelin could also be synthesized in some brain regions, such as the hypothalamus. However, evidences of neuronal production of ghrelin have been inconsistent and, as a consequence, it is still as a matter of debate if ghrelin can be centrally produced. Here, we provide a comprehensive review and discussion of the data supporting, or not, the notion that the mammalian central nervous system can synthetize ghrelin. We conclude that no irrefutable and reproducible evidence exists supporting the notion that ghrelin is synthetized, at physiologically relevant levels, in the central nervous system of adult mammals.

A Simple fMRI Compatible Robotic Stimulator to Study the Neural Mechanisms of Touch and Pain.

PubMed

Riillo, F; Bagnato, C; Allievi, A G; Takagi, A; Fabrizi, L; Saggio, G; Arichi, T; Burdet, E

2016-08-01

This paper presents a simple device for the investigation of the human somatosensory system with functional magnetic imaging (fMRI). PC-controlled pneumatic actuation is employed to produce innocuous or noxious mechanical stimulation of the skin. Stimulation patterns are synchronized with fMRI and other relevant physiological measurements like electroencephalographic activity and vital physiological parameters. The system allows adjustable regulation of stimulation parameters and provides consistent patterns of stimulation. A validation experiment demonstrates that the system safely and reliably identifies clusters of functional activity in brain regions involved in the processing of pain. This new device is inexpensive, portable, easy-to-assemble and customizable to suit different experimental requirements. It provides robust and consistent somatosensory stimulation, which is of crucial importance to investigating the mechanisms of pain and its strong connection with the sense of touch.

Diffusion in Single Supported Lipid Bilayers

NASA Astrophysics Data System (ADS)

Armstrong, C. L.; Trapp, M.; Rheinstädter, M. C.

2011-03-01

Despite their potential relevance for the development of functionalized surfaces and biosensors, the study of single supported membranes using neutron scattering has been limited by the challenge of obtaining relevant dynamic information from a sample with minimal material. Using state of the art neutron instrumentation we have, for the first time, modeled lipid diffusion in single supported lipid bilayers. While we find that the diffusion coefficient for the single bilayer system is comparable to a multi-lamellar lipid system, the molecular mechanism for lipid motion in the single bilayer is a continuous diffusion process with no sign of the flow-like ballistic motion reported in the stacked membrane system. In the future, these membranes will be used to hold and align proteins, mimicking physiological conditions enabling the study of protein structure, function and interactions in relevant and highly topical membrane/protein systems with minimal sample material. C.L. Armstrong, M.D. Kaye, M. Zamponi, E. Mamontov, M. Tyagi, T. Jenkins and M.C. Rheinstädter, Soft Matter Communication, 2010, Advance Article, DOI: 10.1039/C0SM00637H

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy - an illustration with firsthand examples.

PubMed

Zhang, Rui Xue; Li, Jason; Zhang, Tian; Amini, Mohammad A; He, Chunsheng; Lu, Brian; Ahmed, Taksim; Lip, HoYin; Rauth, Andrew M; Wu, Xiao Yu

2018-05-01

Nanotechnology has been applied extensively in drug delivery to improve the therapeutic outcomes of various diseases. Tremendous efforts have been focused on the development of novel nanoparticles and delineation of the physicochemical properties of nanoparticles in relation to their biological fate and functions. However, in the design and evaluation of these nanotechnology-based drug delivery systems, the pharmacology of delivered drugs and the (patho-)physiology of the host have received less attention. In this review, we discuss important pharmacological mechanisms, physiological characteristics, and pathological factors that have been integrated into the design of nanotechnology-enabled drug delivery systems and therapies. Firsthand examples are presented to illustrate the principles and advantages of such integrative design strategies for cancer treatment by exploiting 1) intracellular synergistic interactions of drug-drug and drug-nanomaterial combinations to overcome multidrug-resistant cancer, 2) the blood flow direction of the circulatory system to maximize drug delivery to the tumor neovasculature and cells overexpressing integrin receptors for lung metastases, 3) endogenous lipoproteins to decorate nanocarriers and transport them across the blood-brain barrier for brain metastases, and 4) distinct pathological factors in the tumor microenvironment to develop pH- and oxidative stress-responsive hybrid manganese dioxide nanoparticles for enhanced radiotherapy. Regarding the application in diabetes management, a nanotechnology-enabled closed-loop insulin delivery system was devised to provide dynamic insulin release at a physiologically relevant time scale and glucose levels. These examples, together with other research results, suggest that utilization of the interplay of pharmacology, (patho-)physiology and nanotechnology is a facile approach to develop innovative drug delivery systems and therapies with high efficiency and translational potential.

Attention modifies sound level detection in young children.

PubMed

Sussman, Elyse S; Steinschneider, Mitchell

2011-07-01

Have you ever shouted your child's name from the kitchen while they were watching television in the living room to no avail, so you shout their name again, only louder? Yet, still no response. The current study provides evidence that young children process loudness changes differently than pitch changes when they are engaged in another task such as watching a video. Intensity level changes were physiologically detected only when they were behaviorally relevant, but frequency level changes were physiologically detected without task relevance in younger children. This suggests that changes in pitch rather than changes in volume may be more effective in evoking a response when sounds are unexpected. Further, even though behavioral ability may appear to be similar in younger and older children, attention-based physiologic responses differ from automatic physiologic processes in children. Results indicate that 1) the automatic auditory processes leading to more efficient higher-level skills continue to become refined through childhood; and 2) there are different time courses for the maturation of physiological processes encoding the distinct acoustic attributes of sound pitch and sound intensity. The relevance of these findings to sound perception in real-world environments is discussed.

Endocrine system: part 1.

PubMed

Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

2014-05-27

This article, which forms part of the life sciences series and is the first of two articles on the endocrine system, examines the structure and function of the organs of the endocrine system. It is important that nurses understand how the endocrine system works and its role in maintaining health. The role of the endocrine system and the types, actions and control of hormones are explored. The gross structure of the pituitary and thyroid glands are described along with relevant physiology. Several disorders of the thyroid gland are outlined. The second article examines growth hormone, the pancreas and adrenal glands.

Predicting Drug Concentration‐Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically‐Based Pharmacokinetic Model

PubMed Central

Yamamoto, Yumi; Välitalo, Pyry A.; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; van den Berg, Dirk‐Jan; Hartman, Robin; Wong, Yin Cheong; Danhof, Meindert; van Hasselt, John G. C.

2017-01-01

Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS compartments. System‐specific and drug‐specific model parameters were derived from literature and in silico predictions. The model was validated using detailed concentration‐time profiles from 10 drugs in rat plasma, brain extracellular fluid, 2 cerebrospinal fluid sites, and total brain tissue. These drugs, all small molecules, were selected to cover a wide range of physicochemical properties. The concentration‐time profiles for these drugs were adequately predicted across the CNS compartments (symmetric mean absolute percentage error for the model prediction was <91%). In conclusion, the developed PBPK model can be used to predict temporal concentration profiles of drugs in multiple relevant CNS compartments, which we consider valuable information for efficient CNS drug development. PMID:28891201

Antioxidant Systems are Regulated by Nitric Oxide-Mediated Post-translational Modifications (NO-PTMs)

PubMed Central

Begara-Morales, Juan C.; Sánchez-Calvo, Beatriz; Chaki, Mounira; Valderrama, Raquel; Mata-Pérez, Capilla; Padilla, María N.; Corpas, Francisco J.; Barroso, Juan B.

2016-01-01

Nitric oxide (NO) is a biological messenger that orchestrates a plethora of plant functions, mainly through post-translational modifications (PTMs) such as S-nitrosylation or tyrosine nitration. In plants, hundreds of proteins have been identified as potential targets of these NO-PTMs under physiological and stress conditions indicating the relevance of NO in plant-signaling mechanisms. Among these NO protein targets, there are different antioxidant enzymes involved in the control of reactive oxygen species (ROS), such as H2O2, which is also a signal molecule. This highlights the close relationship between ROS/NO signaling pathways. The major plant antioxidant enzymes, including catalase, superoxide dismutases (SODs) peroxiredoxins (Prx) and all the enzymatic components of the ascorbate-glutathione (Asa-GSH) cycle, have been shown to be modulated to different degrees by NO-PTMs. This mini-review will update the recent knowledge concerning the interaction of NO with these antioxidant enzymes, with a special focus on the components of the Asa-GSH cycle and their physiological relevance. PMID:26909095

Biomimetic fetal rotation bioreactor for engineering bone tissues-Effect of cyclic strains on upregulation of osteogenic gene expression.

PubMed

Ravichandran, Akhilandeshwari; Wen, Feng; Lim, Jing; Chong, Mark Seow Khoon; Chan, Jerry K Y; Teoh, Swee-Hin

2018-04-01

Cells respond to physiological mechanical stresses especially during early fetal development. Adopting a biomimetic approach, it is necessary to develop bioreactor systems to explore the effects of physiologically relevant mechanical strains and shear stresses for functional tissue growth and development. This study introduces a multimodal bioreactor system that allows application of cyclic compressive strains on premature bone grafts that are cultured under biaxial rotation (chamber rotation about 2 axes) conditions for bone tissue engineering. The bioreactor is integrated with sensors for dissolved oxygen levels and pH that allow real-time, non-invasive monitoring of the culture parameters. Mesenchymal stem cells-seeded polycaprolactone-β-tricalcium phosphate scaffolds were cultured in this bioreactor over 2 weeks in 4 different modes-static, cyclic compression, biaxial rotation, and multimodal (combination of cyclic compression and biaxial rotation). The multimodal culture resulted in 1.8-fold higher cellular proliferation in comparison with the static controls within the first week. Two weeks of culture in the multimodal bioreactor utilizing the combined effects of optimal fluid flow conditions and cyclic compression led to the upregulation of osteogenic genes alkaline phosphatase (3.2-fold), osteonectin (2.4-fold), osteocalcin (10-fold), and collagen type 1 α1 (2-fold) in comparison with static cultures. We report for the first time, the independent and combined effects of mechanical stimulation and biaxial rotation for bone tissue engineering using a bioreactor platform with non-invasive sensing modalities. The demonstrated results show leaning towards the futuristic vision of using a physiologically relevant bioreactor system for generation of autologous bone grafts for clinical implantation. Copyright © 2018 John Wiley & Sons, Ltd.

Multiple Stressors in a Changing World: The Need for an Improved Perspective on Physiological Responses to the Dynamic Marine Environment.

PubMed

Gunderson, Alex R; Armstrong, Eric J; Stillman, Jonathon H

2016-01-01

Abiotic conditions (e.g., temperature and pH) fluctuate through time in most marine environments, sometimes passing intensity thresholds that induce physiological stress. Depending on habitat and season, the peak intensity of different abiotic stressors can occur in or out of phase with one another. Thus, some organisms are exposed to multiple stressors simultaneously, whereas others experience them sequentially. Understanding these physicochemical dynamics is critical because how organisms respond to multiple stressors depends on the magnitude and relative timing of each stressor. Here, we first discuss broad patterns of covariation between stressors in marine systems at various temporal scales. We then describe how these dynamics will influence physiological responses to multi-stressor exposures. Finally, we summarize how multi-stressor effects are currently assessed. We find that multi-stressor experiments have rarely incorporated naturalistic physicochemical variation into their designs, and emphasize the importance of doing so to make ecologically relevant inferences about physiological responses to global change.

Enhancement of non-invasive trans-membrane drug delivery using ultrasound and microbubbles during physiologically relevant flow.

PubMed

Shamout, Farah E; Pouliopoulos, Antonios N; Lee, Patrizia; Bonaccorsi, Simone; Towhidi, Leila; Krams, Rob; Choi, James J

2015-09-01

Sonoporation has been associated with drug delivery across cell membranes and into target cells, yet several limitations have prohibited further advancement of this technology. Higher delivery rates were associated with increased cellular death, thus implying a safety-efficacy trade-off. Meanwhile, there has been no reported study of safe in vitro sonoporation in a physiologically relevant flow environment. The objective of our study was not only to evaluate sonoporation under physiologically relevant flow conditions, such as fluid velocity, shear stress and temperature, but also to design ultrasound parameters that exploit the presence of flow to maximize sonoporation efficacy while minimizing or avoiding cellular damage. Human umbilical vein endothelial cells (EA.hy926) were seeded in flow chambers as a monolayer to mimic the endothelium. A peristaltic pump maintained a constant fluid velocity of 12.5 cm/s. A focused 0.5 MHz transducer was used to sonicate the cells, while an inserted focused 7.5 MHz passive cavitation detector monitored microbubble-seeded cavitation emissions. Under these conditions, propidium iodide, which is normally impermeable to the cell membrane, was traced to determine whether it could enter cells after sonication. Meanwhile, calcein-AM was used as a cell viability marker. A range of focused ultrasound parameters was explored, with several unique bioeffects observed: cell detachment, preservation of cell viability with no membrane penetration, cell death and preservation of cell viability with sonoporation. The parameters were then modified further to produce safe sonoporation with minimal cell death. To increase the number of favourable cavitation events, we lowered the ultrasound exposure pressure to 40 kPapk-neg and increased the number of cavitation nuclei by 50 times to produce a trans-membrane delivery rate of 62.6% ± 4.3% with a cell viability of 95% ± 4.2%. Furthermore, acoustic cavitation analysis showed that the low pressure sonication produced stable and non-inertial cavitation throughout the pulse sequence. To our knowledge, this is the first study to demonstrate a high drug delivery rate coupled with high cell viability in a physiologically relevant in vitro flow system. Copyright © 2015. Published by Elsevier Inc.

Biofield Physiology: A Framework for an Emerging Discipline

PubMed Central

Levin, Michael; McCraty, Rollin; Bat, Namuun; Ives, John A.; Lutgendorf, Susan K.; Oschman, James L.

2015-01-01

Biofield physiology is proposed as an overarching descriptor for the electromagnetic, biophotonic, and other types of spatially-distributed fields that living systems generate and respond to as integral aspects of cellular, tissue, and whole organism self-regulation and organization. Medical physiology, cell biology, and biophysics provide the framework within which evidence for biofields, their proposed receptors, and functions is presented. As such, biofields can be viewed as affecting physiological regulatory systems in a manner that complements the more familiar molecular-based mechanisms. Examples of clinically relevant biofields are the electrical and magnetic fields generated by arrays of heart cells and neurons that are detected, respectively, as electrocardiograms (ECGs) or magnetocardiograms (MCGs) and electroencephalograms (EEGs) or magnetoencephalograms (MEGs). At a basic physiology level, electromagnetic activity of neural assemblies appears to modulate neuronal synchronization and circadian rhythmicity. Numerous nonneural electrical fields have been detected and analyzed, including those arising from patterns of resting membrane potentials that guide development and regeneration, and from slowly-varying transepithelial direct current fields that initiate cellular responses to tissue damage. Another biofield phenomenon is the coherent, ultraweak photon emissions (UPE), detected from cell cultures and from the body surface. A physiological role for biophotons is consistent with observations that fluctuations in UPE correlate with cerebral blood flow, cerebral energy metabolism, and EEG activity. Biofield receptors are reviewed in 3 categories: molecular-level receptors, charge flux sites, and endogenously generated electric or electromagnetic fields. In summary, sufficient evidence has accrued to consider biofield physiology as a viable scientific discipline. Directions for future research are proposed. PMID:26665040

Biofield Physiology: A Framework for an Emerging Discipline.

PubMed

Hammerschlag, Richard; Levin, Michael; McCraty, Rollin; Bat, Namuun; Ives, John A; Lutgendorf, Susan K; Oschman, James L

2015-11-01

Biofield physiology is proposed as an overarching descriptor for the electromagnetic, biophotonic, and other types of spatially-distributed fields that living systems generate and respond to as integral aspects of cellular, tissue, and whole organism self-regulation and organization. Medical physiology, cell biology, and biophysics provide the framework within which evidence for biofields, their proposed receptors, and functions is presented. As such, biofields can be viewed as affecting physiological regulatory systems in a manner that complements the more familiar molecular-based mechanisms. Examples of clinically relevant biofields are the electrical and magnetic fields generated by arrays of heart cells and neurons that are detected, respectively, as electrocardiograms (ECGs) or magnetocardiograms (MCGs) and electroencephalograms (EEGs) or magnetoencephalograms (MEGs). At a basic physiology level, electromagnetic activity of neural assemblies appears to modulate neuronal synchronization and circadian rhythmicity. Numerous nonneural electrical fields have been detected and analyzed, including those arising from patterns of resting membrane potentials that guide development and regeneration, and from slowly-varying transepithelial direct current fields that initiate cellular responses to tissue damage. Another biofield phenomenon is the coherent, ultraweak photon emissions (UPE), detected from cell cultures and from the body surface. A physiological role for biophotons is consistent with observations that fluctuations in UPE correlate with cerebral blood flow, cerebral energy metabolism, and EEG activity. Biofield receptors are reviewed in 3 categories: molecular-level receptors, charge flux sites, and endogenously generated electric or electromagnetic fields. In summary, sufficient evidence has accrued to consider biofield physiology as a viable scientific discipline. Directions for future research are proposed.

Novel optical oxy/deoxy hemoglobin monitoring as a modality for non-invasive real-time monitoring of cognitive activity and beyond

NASA Astrophysics Data System (ADS)

Davies-Shaw, Dana; Huser, Thomas R.

2008-02-01

We report on the successful development of a custom in vitro system that provides a physiologically relevant means of demonstrating optical methodologies for the calibration and validation of oxygen delivery and hemoglobin oxygen binding dynamics in the brain. While measured optical signals have generally been equated to heme absorbance values that are, in turn, presumed to correspond to oxygen delivery, there has been little specific study of the sigmoidal oxygen binding dynamics of hemoglobin, a tetrameric protein, within physiologically relevant parameters. Our development of this novel analytical device addresses this issue, and is a significant step towards the minimally invasive and real-time monitoring of spatially resolved cognitive processes. As such, it is of particular interest for the detection of autistic brain activity in infants and young children. Moreover, our device and approach bring with them the ability to quantify and spatially resolve oxygen delivery down to volumes relevant to individual cell oxygen uptake, without any oxygen consumption, and with a temporal resolution that is physically unachievable by any oxygen tracking modality such as fMRI etc. Such a capability opens up myriad possibilities for further investigation, such as real-time tumor biopsy and resection; the tracking and quantification of cellular proliferation, as well as metabolic measures of tissue viability, to name but a few. Our system has also been engineered to be synergistic with virtually all imaging techniques, optical and otherwise.

Modulating kidney transplant interstitial fibrosis and tubular atrophy: is the RAAS an important target?

PubMed

Amer, Hatem; Griffin, Matthew D

2014-02-01

In follow-up to a recently published randomized controlled clinical trial, Issa et al. provide evidence that systemic activity and physiological responsiveness of the renin aldosterone angiotensin system (RAAS) are well within normal limits in most kidney recipients during the first 5 years post-transplant. Implications of the results include the need to better understand intra-renal RAAS activity in transplanted kidneys and to identify patients in which the graft-protective effects of RAAS blockade are most relevant.

Pair Comparison Study of the Relevance of Nine Basic Science Courses

ERIC Educational Resources Information Center

Spilman, Edra L.; Spilman, Helen W.

1975-01-01

Reports a survey study in which basic science courses were rated according to relevance. Notes approaches for making the anatomy disciplines more relevant because results showed them of lowest relevancy compared with physiology, pathology, and pharmacology which were rated of highest relevance and with biochemistry and microbiology which fell…

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective

NASA Astrophysics Data System (ADS)

Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Near-infrared spectroscopy and skeletal muscle oxidative function in vivo in health and disease: a review from an exercise physiology perspective.

PubMed

Grassi, Bruno; Quaresima, Valentina

2016-09-01

In most daily activities related to work or leisure, the energy for muscle work substantially comes from oxidative metabolism. Functional limitations or impairments of this metabolism can significantly affect exercise tolerance and performance. As a method for the functional evaluation of skeletal muscle oxidative metabolism, near-infrared spectroscopy (NIRS) has important strengths but also several limitations, some of which have been overcome by recent technological developments. Skeletal muscle fractional O2 extraction, the main variable which can be noninvasively evaluated by NIRS, is the result of the dynamic balance between O2 utilization and O2 delivery; it can yield relevant information on key physiological and pathophysiological mechanisms, relevant in the evaluation of exercise performance and exercise tolerance in healthy subjects (in normal and in altered environmental conditions) and in patients. In the right hands, NIRS can offer insights into the physiological and pathophysiological adaptations to conditions of increased O2 needs that involve, in an integrated manner, different organs and systems of the body. In terms of patient evaluation, NIRS allows determination of the evolution of the functional impairments, to identify their correlations with clinical symptoms, to evaluate the effects of therapeutic or rehabilitative interventions, and to gain pathophysiological and diagnostic insights.

Red Cell Physiology and Signaling Relevant to the Critical Care Setting

PubMed Central

Said, Ahmed; Rogers, Stephen; Doctor, Allan

2015-01-01

Purpose of Review Oxygen (O2) delivery, the maintenance of which is fundamental to supporting those with critical illness, is a function of blood O2 content and flow. Here, we review red blood cell (RBC) physiology relevant to disordered O2 delivery in the critically ill. Recent Findings Flow (rather then content) is the focus of O2 delivery regulation: O2 content is relatively fixed, whereas flow fluctuates by several orders of magnitude. Thus, blood flow volume and distribution vary to maintain coupling between O2 delivery and demand. The trapping, processing and delivery of nitric oxide (NO) by RBCs has emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We will review conventional RBC physiology influencing O2 delivery (O2 affinity & rheology) and introduce a new paradigm for O2 delivery homeostasis based on coordinated gas transport and vascular signaling by RBCs. Summary By coordinating vascular signaling in a fashion that links O2 and NO flux, RBCs couple vessel caliber (and thus blood flow) to O2 need in tissue. Malfunction of this signaling system is implicated in a wide array of pathophysiologies and may be explanatory for the dysoxia frequently encountered in the critical care setting. PMID:25888155

Red cell physiology and signaling relevant to the critical care setting.

PubMed

Said, Ahmed; Rogers, Stephen; Doctor, Allan

2015-06-01

Oxygen (O2) delivery, the maintenance of which is fundamental to supporting those with critical illness, is a function of blood O2 content and flow. Here, we review red blood cell (RBC) physiology relevant to disordered O2 delivery in the critically ill. Flow (rather than content) is the focus of O2 delivery regulation. O2 content is relatively fixed, whereas flow fluctuates by several orders of magnitude. Thus, blood flow volume and distribution vary to maintain coupling between O2 delivery and demand. The trapping, processing and delivery of nitric oxide (NO) by RBCs has emerged as a conserved mechanism through which regional blood flow is linked to biochemical cues of perfusion sufficiency. We will review conventional RBC physiology that influences O2 delivery (O2 affinity & rheology) and introduce a new paradigm for O2 delivery homeostasis based on coordinated gas transport and vascular signaling by RBCs. By coordinating vascular signaling in a fashion that links O2 and NO flux, RBCs couple vessel caliber (and thus blood flow) to O2 need in tissue. Malfunction of this signaling system is implicated in a wide array of pathophysiologies and may be explanatory for the dysoxia frequently encountered in the critical care setting.

Teaching Stress Physiology Using Zebrafish ("Danio Rerio")

ERIC Educational Resources Information Center

Cooper, Michael; Dhawale, Shree; Mustafa, Ahmed

2009-01-01

A straightforward and inexpensive laboratory experiment is presented that investigates the physiological stress response of zebrafish after a 5 degree C increase in water temperature. This experiment is designed for an undergraduate physiology lab and allows students to learn the scientific method and relevant laboratory techniques without causing…

Characterization of Human Hippocampal Neural Stem/Progenitor Cells and Their Application to Physiologically Relevant Assays for Multiple Ionotropic Glutamate Receptors.

PubMed

Fukushima, Kazuyuki; Tabata, Yoshikuni; Imaizumi, Yoichi; Kohmura, Naohiro; Sugawara, Michiko; Sawada, Kohei; Yamazaki, Kazuto; Ito, Masashi

2014-09-01

The hippocampus is an important brain region that is involved in neurological disorders such as Alzheimer disease, schizophrenia, and epilepsy. Ionotropic glutamate receptors-namely,N-methyl-D-aspartate (NMDA) receptors (NMDARs), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (AMPARs), and kainic acid (KA) receptors (KARs)-are well known to be involved in these diseases by mediating long-term potentiation, excitotoxicity, or both. To predict the therapeutic efficacy and neuronal toxicity of drug candidates acting on these receptors, physiologically relevant systems for assaying brain region-specific human neural cells are necessary. Here, we characterized the functional differentiation of human fetal hippocampus-derived neural stem/progenitor cells-namely, HIP-009 cells. Calcium rise assay demonstrated that, after a 4-week differentiation, the cells responded to NMDA (EC50= 7.5 ± 0.4 µM; n= 4), AMPA (EC50= 2.5 ± 0.1 µM; n= 3), or KA (EC50= 33.5 ± 1.1 µM; n= 3) in a concentration-dependent manner. An AMPA-evoked calcium rise was observed in the absence of the desensitization inhibitor cyclothiazide. In addition, the calcium rise induced by these agonists was inhibited by antagonists for each receptor-namely, MK-801 for NMDA stimulation (IC50= 0.6 ± 0.1 µM; n= 4) and NBQX for AMPA and KA stimulation (IC50= 0.7 ± 0.1 and 0.7 ± 0.03 µM, respectively; n= 3). The gene expression profile of differentiated HIP-009 cells was distinct from that of undifferentiated cells and closely resembled that of the human adult hippocampus. Our results show that HIP-009 cells are a unique tool for obtaining human hippocampal neural cells and are applicable to systems for assay of ionotropic glutamate receptors as a physiologically relevant in vitro model. © 2014 Society for Laboratory Automation and Screening.

Isolated heart models: cardiovascular system studies and technological advances.

PubMed

Olejnickova, Veronika; Novakova, Marie; Provaznik, Ivo

2015-07-01

Isolated heart model is a relevant tool for cardiovascular system studies. It represents a highly reproducible model for studying broad spectrum of biochemical, physiological, morphological, and pharmaceutical parameters, including analysis of intrinsic heart mechanics, metabolism, and coronary vascular response. Results obtained in this model are under no influence of other organ systems, plasma concentration of hormones or ions and influence of autonomic nervous system. The review describes various isolated heart models, the modes of heart perfusion, and advantages and limitations of various experimental setups. It reports the improvements of perfusion setup according to Langendorff introduced by the authors.

The digestive system: part 1.

PubMed

Johnstone, Carolyn; Hendry, Charles; Farley, Alistair; McLafferty, Ella

This article, which forms part of the life sciences series and is the first of two articles on the digestive system, explores the structure and function of the digestive system. It is important that nurses understand how the digestive system works and its role in maintaining health. The article describes the gross structure of the gastrointestinal tract along with relevant physiology. It also outlines several disorders of the gastrointestinal tract and their treatment and nursing management. The second article will explain the liver, pancreas and gall bladder and their digestive functions, and provides a brief overview of the disorders of chronic liver disease, pancreatitis and gallstones.

A novel Minimalist Cell-Free MHC Class II Antigen Processing System Identifies Immunodominant Epitopes

PubMed Central

Hartman, Isamu Z.; Kim, AeRyon; Cotter, Robert J.; Walter, Kimberly; Dalai, Sarat K.; Boronina, Tatiana; Griffith, Wendell; Schwenk, Robert; Lanar, David E.; Krzych, Urszula; Cole, Robert N.; Sadegh-Nasseri, Scheherazade

2010-01-01

Immunodominance is defined as restricted responsiveness of T cells to a few selected epitopes from complex antigens. Strategies currently used for elucidating CD4+ T cell epitopes are inadequate. To understand the mechanism of epitope selection for helper T cells, we established a cell-free antigen processing system composed of defined proteins: MHC class II, cathepsins, and HLA-DM. Our minimalist system successfully identified the physiologically selected immunodominant epitopes of model antigens, HA1 from influenza virus (A/Texas/1/77) and type II collagen. When applied for de novo epitope identification to a malaria antigen, or HA1 from H5N1 virus (Avian Flu), the system selected a single epitope from each protein that were confirmed to be immunodominant by their capacity to activate CD4+ T cells in HLA-DR1 positive human volunteers or transgenic mice immunized with the corresponding proteins. Thus, we provide a powerful new tool for the identification of physiologically relevant helper T cell epitopes from antigens. PMID:21037588

The cardiovascular system after exercise.

PubMed

Romero, Steven A; Minson, Christopher T; Halliwill, John R

2017-04-01

Recovery from exercise refers to the time period between the end of a bout of exercise and the subsequent return to a resting or recovered state. It also refers to specific physiological processes or states occurring after exercise that are distinct from the physiology of either the exercising or the resting states. In this context, recovery of the cardiovascular system after exercise occurs across a period of minutes to hours, during which many characteristics of the system, even how it is controlled, change over time. Some of these changes may be necessary for long-term adaptation to exercise training, yet some can lead to cardiovascular instability during recovery. Furthermore, some of these changes may provide insight into when the cardiovascular system has recovered from prior training and is physiologically ready for additional training stress. This review focuses on the most consistently observed hemodynamic adjustments and the underlying causes that drive cardiovascular recovery and will highlight how they differ following resistance and aerobic exercise. Primary emphasis will be placed on the hypotensive effect of aerobic and resistance exercise and associated mechanisms that have clinical relevance, but if left unchecked, can progress to symptomatic hypotension and syncope. Finally, we focus on the practical application of this information to strategies to maximize the benefits of cardiovascular recovery, or minimize the vulnerabilities of this state. We will explore appropriate field measures, and discuss to what extent these can guide an athlete's training. Copyright © 2017 the American Physiological Society.

Using in vitro models for expression profiling studies on ethanol and drugs of abuse.

PubMed

Thibault, Christelle; Hassan, Sajida; Miles, Michael

2005-03-01

The use of expression profiling with microarrays offers great potential for studying the mechanisms of action of drugs of abuse. Studies with the intact nervous system seem likely to be most relevant to understanding the mechanisms of drug abuse-related behaviours. However, the use of expression profiling with in vitro culture models offers significant advantages for identifying details of cellular signalling actions and toxicity for drugs of abuse. This study discusses general issues of the use of microarrays and cell culture models for studies on drugs of abuse. Specific results from existing studies are also discussed, providing clear examples of relevance for in vitro studies on ethanol, nicotine, opiates, cannabinoids and hallucinogens such as LSD. In addition to providing details on signalling mechanisms relevant to the neurobiology of drugs of abuse, microarray studies on a variety of cell culture systems have also provided important information on mechanisms of cellular/organ toxicity with drugs of abuse. Efforts to integrate genomic studies on drugs of abuse with both in vivo and in vitro models offer the potential for novel mechanistic rigor and physiological relevance.

Models and signal processing for an implanted ethanol bio-sensor.

PubMed

Han, Jae-Joon; Doerschuk, Peter C; Gelfand, Saul B; O'Connor, Sean J

2008-02-01

The understanding of drinking patterns leading to alcoholism has been hindered by an inability to unobtrusively measure ethanol consumption over periods of weeks to months in the community environment. An implantable ethanol sensor is under development using microelectromechanical systems technology. For safety and user acceptability issues, the sensor will be implanted subcutaneously and, therefore, measure peripheral-tissue ethanol concentration. Determining ethanol consumption and kinetics in other compartments from the time course of peripheral-tissue ethanol concentration requires sophisticated signal processing based on detailed descriptions of the relevant physiology. A statistical signal processing system based on detailed models of the physiology and using extended Kalman filtering and dynamic programming tools is described which can estimate the time series of ethanol concentration in blood, liver, and peripheral tissue and the time series of ethanol consumption based on peripheral-tissue ethanol concentration measurements.

Battery-free, wireless sensors for full-body pressure and temperature mapping

PubMed Central

Han, Seungyong; Kim, Jeonghyun; Won, Sang Min; Ma, Yinji; Kang, Daeshik; Xie, Zhaoqian; Lee, Kyu-Tae; Chung, Ha Uk; Banks, Anthony; Min, Seunghwan; Heo, Seung Yun; Davies, Charles R.; Lee, Jung Woo; Lee, Chi-Hwan; Kim, Bong Hoon; Li, Kan; Zhou, Yadong; Wei, Chen; Feng, Xue; Huang, Yonggang; Rogers, John A.

2018-01-01

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers. PMID:29618561

A Systems Approach to Stress, Stressors and Resilience in Humans

PubMed Central

Oken, Barry S.; Chamine, Irina; Wakeland, Wayne

2014-01-01

The paper focuses on the biology of stress and resilience and their biomarkers in humans from the system science perspective. A stressor pushes the physiological system away from its baseline state towards a lower utility state. The physiological system may return towards the original state in one attractor basin but may be shifted to a state in another, lower utility attractor basin. While some physiological changes induced by stressors may benefit health, there is often a chronic wear and tear cost due to implementing changes to enable the return of the system to its baseline state and maintain itself in the high utility baseline attractor basin following repeated perturbations. This cost, also called allostatic load, is the utility reduction associated with both a change in state and with alterations in the attractor basin that affect system responses following future perturbations. This added cost can increase the time course of the return to baseline or the likelihood of moving into a different attractor basin following a perturbation. Opposite to this is the system’s resilience which influences its ability to return to the high utility attractor basin following a perturbation by increasing the likelihood and/or speed of returning to the baseline state following a stressor. This review paper is a qualitative systematic review; it covers areas most relevant for moving the stress and resilience field forward from a more quantitative and neuroscientific perspective. PMID:25549855

Microphysiological modeling of the reproductive tract: a fertile endeavor.

PubMed

Eddie, Sharon L; Kim, J Julie; Woodruff, Teresa K; Burdette, Joanna E

2014-09-01

Preclinical toxicity testing in animal models is a cornerstone of the drug development process, yet it is often unable to predict adverse effects and tolerability issues in human subjects. Species-specific responses to investigational drugs have led researchers to utilize human tissues and cells to better estimate human toxicity. Unfortunately, human cell-derived models are imperfect because toxicity is assessed in isolation, removed from the normal physiologic microenvironment. Microphysiological modeling often referred to as 'organ-on-a-chip' or 'human-on-a-chip' places human tissue into a microfluidic system that mimics the complexity of human in vivo physiology, thereby allowing for toxicity testing on several cell types, tissues, and organs within a more biologically relevant environment. Here we describe important concepts when developing a repro-on-a-chip model. The development of female and male reproductive microfluidic systems is critical to sex-based in vitro toxicity and drug testing. This review addresses the biological and physiological aspects of the male and female reproductive systems in vivo and what should be considered when designing a microphysiological human-on-a-chip model. Additionally, interactions between the reproductive tract and other systems are explored, focusing on the impact of factors and hormones produced by the reproductive tract and disease pathophysiology. © 2014 by the Society for Experimental Biology and Medicine.

Electrotactile and vibrotactile displays for sensory substitution systems

NASA Technical Reports Server (NTRS)

Kaczmarek, Kurt A.; Webster, John G.; Bach-Y-rita, Paul; Tompkins, Willis J.

1991-01-01

Sensory substitution systems provide their users with environmental information through a human sensory channel (eye, ear, or skin) different from that normally used or with the information processed in some useful way. The authors review the methods used to present visual, auditory, and modified tactile information to the skin and discuss present and potential future applications of sensory substitution, including tactile vision substitution (TVS), tactile auditory substitution, and remote tactile sensing or feedback (teletouch). The relevant sensory physiology of the skin, including the mechanisms of normal touch and the mechanisms and sensations associated with electrical stimulation of the skin using surface electrodes (electrotactile, or electrocutaneous, stimulation), is reviewed. The information-processing ability of the tactile sense and its relevance to sensory substitution is briefly summarized. The limitations of current tactile display technologies are discussed.

Depressive symptoms and attenuated physiological reactivity to laboratory stressors.

PubMed

Schwerdtfeger, Andreas; Rosenkaimer, Ann-Kathrin

2011-07-01

There is evidence that depressive symptoms are associated with attenuated physiological reactivity to active stressors. However, it is not known whether blunted reactivity in depressed individuals is stressor-specific. We examined cardiovascular and electrodermal reactivity in non-clinical participants with varying levels of depressive symptoms to different active and passive stressors. Depressive symptoms were inversely related to both blood pressure and skin conductance reactivity during a public speaking task and the viewing of the speech video. However, no effects were found during a cold pressor task. Together these findings suggest that depressive symptoms are related to attenuated sympathetic nervous system reactivity in response to self-relevant stressors. Copyright © 2011 Elsevier B.V. All rights reserved.

The formation of quiescent glomerular endothelial cell monolayer in vitro is strongly dependent on the choice of extracellular matrix coating

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

Pajęcka, Kamilla, E-mail: kpaj@novonordisk.com; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus; Nielsen, Malik Nygaard

Background and aims: Nephropathy involves pathophysiological changes to the glomerulus. The primary glomerular endothelial cells (GEnCs) have emerged as an important tool for studying glomerulosclerotic mechanisms and in the screening process for drug-candidates. The success of the studies is dependent on the quality of the cell model. Therefore, we set out to establish an easy, reproducible model of the quiescent endothelial monolayer with the use of commercially available extracellular matrices (ECMs). Methods: Primary hGEnCs were seeded on various ECMs. Cell adhesion was monitored by an impedance sensing system. The localization of junctional proteins was assessed by immunofluorescence and the barriermore » function by passage of fluorescent dextrans and magnitude of VEGF response. Results: All ECM matrices except recombinant human laminin 111 (rhLN111) supported comparable cell proliferation. Culturing hGEnCs on rhLN521, rhLN511 or fibronectin resulted in a physiologically relevant barrier to 70 kDa dextrans which was 82% tighter than that formed on collagen type IV. Furthermore, only hGEnCs cultured on rhLN521 or rhLN511 showed plasma-membrane localized zonula occludens-1 and vascular endothelial cadherin indicative of proper tight and adherens junctions (AJ). Conclusion: We recommend culturing hGEnCs on the mature glomerular basement membrane laminin - rhLN521 – which, as the only commercially available ECM, promotes all of the characteristics of the quiescent hGEnC monolayer: cobblestone morphology, well-defined AJs and physiological perm-selectivity. - Highlights: • rhLN521, rhLN511 and hFN assure physiologically relevant permeability. • rhLN521 and rhLN511 ensure best cell morphology and adherens junction formation. • Collagen IV and I based coating results in disorganized hGEnC monolayer. • Physiologically relevant ECM may lead to down-regulation of self-produced matrices.« less

Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade.

PubMed

Vasconcelos, Mailton; Stein, Dirson João; de Almeida, Rosa Maria M

2015-01-01

Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior. A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors. Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology. The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.

Physiological responses and gene expression changes in the western mosquitofish (Gambusia affinis) exposed to progesterone at environmentally relevant concentrations.

PubMed

Hou, Liping; Xu, Hongyan; Ying, Guangguo; Yang, Yang; Shu, Hu; Zhao, Jianliang; Cheng, Xuemei

2017-11-01

Progesterone (P4) is a natural and synthetic steroid, widely distributed in the aquatic environments. It can lead to adverse effects on the endocrine system in aquatic organisms. This study investigated the toxicological effects of exposure to environmentally relevant concentrations (4, 44, and 410ng/L) of progesterone for 42 d on adult female mosquitofish, Gambusia affinis. We performed morphological and histological analyses on gonads, anal fins, liver, and gills after the exposure of mosquito fish to P4. The expression levels of genes (vtg, er, and ar isoforms) related to fish reproduction and detoxification (cyp1a) in the liver were quantified by quantitative real-time polymerase chain reaction. The results showed that the progesterone exposure induced slight masculinization in female mosquitofish, influenced the oocyte maturation as revealed by histology of the ovaries, and caused severe damages to the liver and gills of adult female mosquitofish. It also suppressed the mRNAs expression of vtg, er, cyp1a, and significantly enhanced the expression of ar mRNA in the liver. This study reveals the molecular and physiological effects of progesterone at environmentally relevant concentrations, which might further be translated to alterations in the reproduction of mosquitofish. Copyright © 2017 Elsevier B.V. All rights reserved.

Interactions of hydroxyapatite surfaces: conditioning films of human whole saliva.

PubMed

Cárdenas, Marité; Valle-Delgado, Juan José; Hamit, Jildiz; Rutland, Mark W; Arnebrant, Thomas

2008-07-15

Hydroxyapatite is a very interesting material given that it is the main component in tooth enamel and because of its uses in bone implant applications. Therefore, not only the characterization of its surface is of high relevance but also designing reliable methods to study the interfacial properties of films adsorbed onto it. In this paper we apply the colloidal probe atomic force microscopy method to investigate the surface properties of commercially available hydroxyapatite surfaces (both microscopic particles and macroscopic discs) in terms of interfacial and frictional forces. In this way, we find that hydroxyapatite surfaces at physiological relevant conditions are slightly negatively charged. The surfaces were then exposed to human whole saliva, and the surface properties were re-evaluated. A thick film was formed that was very resistant to mechanical stress. The frictional measurements demonstrated that the film was indeed highly lubricating, supporting the argument that this system may prove to be a relevant model for evaluating dental and implant systems.

Frontiers in the Teaching of Physiology. Computer Literacy and Simulation.

ERIC Educational Resources Information Center

Tidball, Charles S., Ed.; Shelesnyak, M. C., Ed.

Provided is a collection of papers on computer literacy and simulation originally published in The Physiology Teacher, supplemented by additional papers and a glossary of terms relevant to the field. The 12 papers are presented in five sections. An affirmation of conventional physiology laboratory exercises, coping with computer terminology, and…

Identification of complex metabolic states in critically injured patients using bioinformatic cluster analysis.

PubMed

Cohen, Mitchell J; Grossman, Adam D; Morabito, Diane; Knudson, M Margaret; Butte, Atul J; Manley, Geoffrey T

2010-01-01

Advances in technology have made extensive monitoring of patient physiology the standard of care in intensive care units (ICUs). While many systems exist to compile these data, there has been no systematic multivariate analysis and categorization across patient physiological data. The sheer volume and complexity of these data make pattern recognition or identification of patient state difficult. Hierarchical cluster analysis allows visualization of high dimensional data and enables pattern recognition and identification of physiologic patient states. We hypothesized that processing of multivariate data using hierarchical clustering techniques would allow identification of otherwise hidden patient physiologic patterns that would be predictive of outcome. Multivariate physiologic and ventilator data were collected continuously using a multimodal bioinformatics system in the surgical ICU at San Francisco General Hospital. These data were incorporated with non-continuous data and stored on a server in the ICU. A hierarchical clustering algorithm grouped each minute of data into 1 of 10 clusters. Clusters were correlated with outcome measures including incidence of infection, multiple organ failure (MOF), and mortality. We identified 10 clusters, which we defined as distinct patient states. While patients transitioned between states, they spent significant amounts of time in each. Clusters were enriched for our outcome measures: 2 of the 10 states were enriched for infection, 6 of 10 were enriched for MOF, and 3 of 10 were enriched for death. Further analysis of correlations between pairs of variables within each cluster reveals significant differences in physiology between clusters. Here we show for the first time the feasibility of clustering physiological measurements to identify clinically relevant patient states after trauma. These results demonstrate that hierarchical clustering techniques can be useful for visualizing complex multivariate data and may provide new insights for the care of critically injured patients.

The mystery of membrane organization: composition, regulation and physiological relevance of lipid rafts

PubMed Central

Sezgin, Erdinc; Levental, Ilya; Mayor, Satyajit; Eggeling, Christian

2017-01-01

Cellular plasma membranes are laterally heterogeneous, featuring a variety of distinct subcompartments that differ in their biophysical properties and composition. A large body of research has focused on understanding the basis for this heterogeneity and its physiological relevance. The membrane raft hypothesis formalized a physicochemical principle for a subtype of such lateral membrane heterogeneity, wherein the preferential associations of cholesterol and saturated lipids drives the formation of relatively packed (ordered) membrane domains that selectively recruit certain lipids and proteins. Recent years have yielded new insights into this concept and its in vivo relevance, primarily owing to the development of biochemical and biophysical technologies. PMID:28356571

Retrieval practice in the form of online homework improved information retention more when spaced 5 days rather than 1 day after class in two physiology courses.

PubMed

Cadaret, Caitlin N; Yates, Dustin T

2018-06-01

Studies have shown that practicing temporally spaced retrieval of previously learned information via formal assessments increases student retention of the information. Our objective was to determine the impact of online homework administered as a first retrieval practice 1 or 5 days after introduction of physiology topics on long-term information retention. Students in two undergraduate courses, Anatomy and Physiology (ASCI 240) and Animal Physiological Systems (ASCI 340), were presented with information on a specific physiological system during each weekly laboratory and then completed an online homework assignment either 1 or 5 days later. Information retention was assessed via an in-class quiz the following week and by a comprehensive final exam at semester's end (4-13 wk later). Performance on homework assignments was generally similar between groups for both courses. Information retention at 1 wk did not differ due to timing of homework in either course. In both courses, however, students who received homework 5 days after class performed better on final exam questions relevant to that week's topic compared with their day 1 counterparts. These findings indicate that the longer period between introducing physiology information in class and assigning the first retrieval practice was more beneficial to long-term information retention than the shorter period, despite seemingly equivalent benefits in the shorter term. Since information is typically forgotten over time, we speculate that the longer interval necessitates greater retrieval effort in much the same way as built-in desirable difficulties, thus allowing for stronger conceptual connections and deeper comprehension.

Physiological mechanisms underlying animal social behaviour.

PubMed

Seebacher, Frank; Krause, Jens

2017-08-19

Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission-fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments.This article is part of the themed issue 'Physiological determinants of social behaviour in animals'. © 2017 The Author(s).

Physiological mechanisms underlying animal social behaviour

PubMed Central

2017-01-01

Many species of animal live in groups, and the group represents the organizational level within which ecological and evolutionary processes occur. Understanding these processes, therefore, relies on knowledge of the mechanisms that permit or constrain group formation. We suggest that physiological capacities and differences in physiology between individuals modify fission–fusion dynamics. Differences between individuals in locomotor capacity and metabolism may lead to fission of groups and sorting of individuals into groups with similar physiological phenotypes. Environmental impacts such as hypoxia can influence maximum group sizes and structure in fish schools by altering access to oxygenated water. The nutritional environment determines group cohesion, and the increase in information collected by the group means that individuals should rely more on social information and form more cohesive groups in uncertain environments. Changing environmental contexts require rapid responses by individuals to maintain group coordination, which are mediated by neuroendocrine signalling systems such as nonapeptides and steroid hormones. Brain processing capacity may constrain social complexity by limiting information processing. Failure to evaluate socially relevant information correctly limits social interactions, which is seen, for example, in autism. Hence, functioning of a group relies to a large extent on the perception and appropriate processing of signals from conspecifics. Many if not all physiological systems are mechanistically linked, and therefore have synergistic effects on social behaviour. A challenge for the future lies in understanding these interactive effects, which will improve understanding of group dynamics, particularly in changing environments. This article is part of the themed issue ‘Physiological determinants of social behaviour in animals’. PMID:28673909

When pain and hunger collide; psychological influences on differences in brain activity during physiological and non-physiological gastric distension.

PubMed

Coen, S J

2011-06-01

Functional neuroimaging has been used extensively in conjunction with gastric balloon distension in an attempt to unravel the relationship between the brain, regulation of hunger, satiety, and food intake tolerance. A number of researchers have also adopted a more physiological approach using intra-gastric administration of a liquid meal which has revealed different brain responses to gastric balloon distension. These differences are important as they question the utility and relevance of non-physiological models such as gastric balloon distension, especially when investigating mechanisms of feeding behavior such as satiety. However, an assessment of the relevance of physiological versus non-physiological gastric distension has been problematic due to differences in distension volumes between studies. In this issue of Neurogastroenterology and Motility, Geeraerts et al. compare brain activity during volume matched nutrient gastric distension and balloon distension in healthy volunteers. Gastric balloon distension activated the 'visceral pain neuromatrix'. This network of brain regions was deactivated during nutrient infusion, supporting the notion that brain activity during physiological versus non-physiological distension is indeed different. The authors suggest deactivation of the pain neuromatrix during nutrient infusion serves as a prerequisite for tolerance of normal meal volumes in health. © 2011 Blackwell Publishing Ltd.

Supra-physiological folic acid concentrations induce aberrant DNA methylation in normal human cells in vitro.

PubMed

Charles, Michelle A; Johnson, Ian T; Belshaw, Nigel J

2012-07-01

The micronutrients folate and selenium may modulate DNA methylation patterns by affecting intracellular levels of the methyl donor S-adenosylmethionine (SAM) and/or the product of methylation reactions S-adenosylhomocysteine (SAH). WI-38 fibroblasts and FHC colon epithelial cells were cultured in the presence of two forms of folate or four forms of selenium at physiologically-relevant doses, and their effects on LINE-1 methylation, gene-specific CpG island (CGI) methylation and intracellular SAM:SAH were determined. At physiologically-relevant doses the forms of folate or selenium had no effect on LINE-1 or CGI methylation, nor on intracellular SAM:SAH. However the commercial cell culture media used for the selenium studies, containing supra-physiological concentrations of folic acid, induced LINE-1 hypomethylation, CGI hypermethylation and decreased intracellular SAM:SAH in both cell lines. We conclude that the exposure of normal human cells to supra-physiological folic acid concentrations present in commercial cell culture media perturbs the intracellular SAM:SAH ratio and induces aberrant DNA methylation.

Oxygen demand of perfused heart preparations: how electromechanical function and inadequate oxygenation affect physiology and optical measurements.

PubMed

Kuzmiak-Glancy, Sarah; Jaimes, Rafael; Wengrowski, Anastasia M; Kay, Matthew W

2015-06-01

What is the topic of this review? This review discusses how the function and electrophysiology of isolated perfused hearts are affected by oxygenation and energy utilization. The impact of oxygenation on fluorescence measurements in perfused hearts is also discussed. What advances does it highlight? Recent studies have illuminated the inherent differences in electromechanical function, energy utilization rate and oxygen requirements between the primary types of excised heart preparations. A summary and analysis of how these variables affect experimental results are necessary to elevate the physiological relevance of these approaches in order to advance the field of whole-heart research. The ex vivo perfused heart recreates important aspects of in vivo conditions to provide insight into whole-organ function. In this review we discuss multiple types of ex vivo heart preparations, explain how closely each mimic in vivo function, and discuss how changes in electromechanical function and inadequate oxygenation of ex vivo perfused hearts may affect measurements of physiology. Hearts that perform physiological work have high oxygen demand and are likely to experience hypoxia when perfused with a crystalloid perfusate. Adequate myocardial oxygenation is critically important for obtaining physiologically relevant measurements, so when designing experiments the type of ex vivo preparation and the capacity of perfusate to deliver oxygen must be carefully considered. When workload is low, such as during interventions that inhibit contraction, oxygen demand is also low, which could dramatically alter a physiological response to experimental variables. Changes in oxygenation also alter the optical properties of cardiac tissue, an effect that may influence optical signals measured from both endogenous and exogenous fluorophores. Careful consideration of oxygen supply, working condition, and wavelengths used to acquire optical signals is critical for obtaining physiologically relevant measurements during ex vivo perfused heart studies. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

Intercellular and systemic spread of RNA and RNAi in plants.

PubMed

Nazim Uddin, Mohammad; Kim, Jae-Yean

2013-01-01

Plants possess dynamic networks of intercellular communication that are crucial for plant development and physiology. In plants, intercellular communication involves a combination of ligand-receptor-based apoplasmic signaling, and plasmodesmata and phloem-mediated symplasmic signaling. The intercellular trafficking of macromolecules, including RNAs and proteins, has emerged as a novel mechanism of intercellular communication in plants. Various forms of regulatory RNAs move over distinct cellular boundaries through plasmodesmata and phloem. This plant-specific, non-cell-autonomous RNA trafficking network is also involved in development, nutrient homeostasis, gene silencing, pathogen defense, and many other physiological processes. However, the mechanism underlying macromolecular trafficking in plants remains poorly understood. Current progress made in RNA trafficking research and its biological relevance to plant development will be summarized. Diverse plant regulatory mechanisms of cell-to-cell and systemic long-distance transport of RNAs, including mRNAs, viral RNAs, and small RNAs, will also be discussed. Copyright © 2013 John Wiley & Sons, Ltd.

Niche-based screening identifies small-molecule inhibitors of leukemia stem cells.

PubMed

Hartwell, Kimberly A; Miller, Peter G; Mukherjee, Siddhartha; Kahn, Alissa R; Stewart, Alison L; Logan, David J; Negri, Joseph M; Duvet, Mildred; Järås, Marcus; Puram, Rishi; Dancik, Vlado; Al-Shahrour, Fatima; Kindler, Thomas; Tothova, Zuzana; Chattopadhyay, Shrikanta; Hasaka, Thomas; Narayan, Rajiv; Dai, Mingji; Huang, Christina; Shterental, Sebastian; Chu, Lisa P; Haydu, J Erika; Shieh, Jae Hung; Steensma, David P; Munoz, Benito; Bittker, Joshua A; Shamji, Alykhan F; Clemons, Paul A; Tolliday, Nicola J; Carpenter, Anne E; Gilliland, D Gary; Stern, Andrew M; Moore, Malcolm A S; Scadden, David T; Schreiber, Stuart L; Ebert, Benjamin L; Golub, Todd R

2013-12-01

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on target, via inhibition of HMG-CoA reductase. These results illustrate the power of merging physiologically relevant models with high-throughput screening.

Complex biomembrane mimetics on the sub-nanometer scale

DOE PAGES

Heberle, Frederick A.; Pabst, Georg

2017-07-17

Biomimetic lipid vesicles are indispensable tools for gaining insight into the biophysics of cell physiology on the molecular level. The level of complexity of these model systems has steadily increased, and now spans from domain forming lipid mixtures to asymmetric lipid bilayers. We review recent progress in the development and application of elastic neutron and X-ray scattering techniques for studying these systems in situ and under physiologically relevant conditions on the nanometer to sub-nanometer length scales. Particularly we focus on: (i) structural details of coexisting liquid-ordered and liquid-disordered domains, including their thickness and lipid packing mismatch as a function ofmore » a size transition from nanoscopic to macroscopic domains; (ii) membrane-mediated protein partitioning into lipid domains; (iii) the role of the aqueous medium in tuning interactions between membranes and domains; and (iv) leaflet specific structure in asymmetric bilayers and passive lipid flip-flop.« less

Complex biomembrane mimetics on the sub-nanometer scale

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

Heberle, Frederick A.; Pabst, Georg

Biomimetic lipid vesicles are indispensable tools for gaining insight into the biophysics of cell physiology on the molecular level. The level of complexity of these model systems has steadily increased, and now spans from domain forming lipid mixtures to asymmetric lipid bilayers. We review recent progress in the development and application of elastic neutron and X-ray scattering techniques for studying these systems in situ and under physiologically relevant conditions on the nanometer to sub-nanometer length scales. Particularly we focus on: (i) structural details of coexisting liquid-ordered and liquid-disordered domains, including their thickness and lipid packing mismatch as a function ofmore » a size transition from nanoscopic to macroscopic domains; (ii) membrane-mediated protein partitioning into lipid domains; (iii) the role of the aqueous medium in tuning interactions between membranes and domains; and (iv) leaflet specific structure in asymmetric bilayers and passive lipid flip-flop.« less

Niche-based screening identifies small-molecule inhibitors of leukemia stem cells

PubMed Central

Mukherjee, Siddhartha; Kahn, Alissa R; Stewart, Alison L; Logan, David J; Negri, Joseph M; Duvet, Mildred; Järås, Marcus; Puram, Rishi; Dancik, Vlado; Al-Shahrour, Fatima; Kindler, Thomas; Tothova, Zuzana; Chattopadhyay, Shrikanta; Hasaka, Thomas; Narayan, Rajiv; Dai, Mingji; Huang, Christina; Shterental, Sebastian; Chu, Lisa P; Haydu, J Erika; Shieh, Jae Hung; Steensma, David P; Munoz, Benito; Bittker, Joshua A; Shamji, Alykhan F; Clemons, Paul A; Tolliday, Nicola J; Carpenter, Anne E; Gilliland, D Gary; Stern, Andrew M; Moore, Malcolm A S; Scadden, David T; Schreiber, Stuart L; Ebert, Benjamin L; Golub, Todd R

2014-01-01

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone-marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on-target, via inhibition of HMGCoA reductase. These results illustrate the power of merging physiologically-relevant models with high-throughput screening. PMID:24161946

Blood Pressure Regulation: Every Adaptation is an Integration?

PubMed Central

Joyner, Michael J.; Limberg, Jacqueline K.

2013-01-01

This focused review serves to explore relevant issues in regard to blood pressure regulation and by doing so, provides the initial stimulus paper for the Thematic Review series “Blood Pressure Regulation” to be published in the European Journal of Applied Physiology over the coming months. In this introduction, we highlight how variable normal blood pressure can be and challenge the reader to take another look at some key concepts related to blood pressure regulation. We point out that there is frequently an underappreciated balance between peripheral vasodilation and systemic blood pressure regulation and ask the question: Are changes in blood pressure, in effect, reasonable and integrated adaptations to the physiological challenge at hand? We conclude with the idea that blood pressure regulatory systems are both flexible and redundant; ensuring a wide variety of activities associated with life can be accompanied by a perfusion pressure that can serve multiple masters. PMID:23558925

Kv1.5 in the immune system: the good, the bad, or the ugly?

PubMed

Felipe, Antonio; Soler, Concepció; Comes, Núria

2010-01-01

For the last 20 years, knowledge of the physiological role of voltage-dependent potassium channels (Kv) in the immune system has grown exponentially. Leukocytes express a limited repertoire of Kv channels, which contribute to the membrane potential. These proteins are involved in the immune response and are therefore considered good pharmacological targets. Although there is a clear consensus about the physiological relevance of Kv1.3, the expression and the role of Kv1.5 are controversial. However, recent reports indicate that certain heteromeric Kv1.3/Kv1.5 associations may provide insight on Kv1.5. Here, we summarize what is known about this issue and highlight the role of Kv1.5 partnership interactions that could be responsible for this debate. The Kv1.3/Kv1.5 heterotetrameric composition of the channel and their possible differential associations with accessory regulatory proteins warrant further investigation.

Activation of cellular death programs associated with immunosenescence-like phenotype in TPPII knockout mice

PubMed Central

Huai, Jisen; Firat, Elke; Nil, Ahmed; Million, Daniele; Gaedicke, Simone; Kanzler, Benoit; Freudenberg, Marina; van Endert, Peter; Kohler, Gabriele; Pahl, Heike L.; Aichele, Peter; Eichmann, Klaus; Niedermann, Gabriele

2008-01-01

The giant cytosolic protease tripeptidyl peptidase II (TPPII) has been implicated in the regulation of proliferation and survival of malignant cells, particularly lymphoma cells. To address its functions in normal cellular and systemic physiology we have generated TPPII-deficient mice. TPPII deficiency activates cell type-specific death programs, including proliferative apoptosis in several T lineage subsets and premature cellular senescence in fibroblasts and CD8+ T cells. This coincides with up-regulation of p53 and dysregulation of NF-κB. Prominent degenerative alterations at the organismic level were a decreased lifespan and symptoms characteristic of immunohematopoietic senescence. These symptoms include accelerated thymic involution, lymphopenia, impaired proliferative T cell responses, extramedullary hematopoiesis, and inflammation. Thus, TPPII is important for maintaining normal cellular and systemic physiology, which may be relevant for potential therapeutic applications of TPPII inhibitors. PMID:18362329

A Microfabricated Platform for Generating Physiologically-Relevant Hepatocyte Zonation

NASA Astrophysics Data System (ADS)

McCarty, William J.; Usta, O. Berk; Yarmush, Martin L.

2016-05-01

In vitro liver models have been important tools for more than 40 years for academic research and preclinical toxicity screening by the pharmaceutical industry. Hepatocytes, the highly metabolic parenchymal cells of the liver, are efficient at different metabolic chemistries depending on their relative spatial location along the sinusoid from the portal triad to the central vein. Although replicating hepatocyte metabolic zonation is vitally important for physiologically-relevant in vitro liver tissue and organ models, it is most often completely overlooked. Here, we demonstrate the creation of spatially-controlled zonation across multiple hepatocyte metabolism levels through the application of precise concentration gradients of exogenous hormone (insulin and glucagon) and chemical (3-methylcholanthrene) induction agents in a microfluidic device. Observed gradients in glycogen storage via periodic acid-Schiff staining, urea production via carbamoyl phosphatase synthetase I staining, and cell viability after exposure to allyl alcohol and acetaminophen demonstrated the in vitro creation of hepatocyte carbohydrate, nitrogen, alcohol degradation, and drug conjugation metabolic zonation. This type of advanced control system will be crucial for studies evaluating drug metabolism and toxicology using in vitro constructs.

Correlation between vortices and wall shear stress in a curved artery model under pulsatile flow conditions

NASA Astrophysics Data System (ADS)

Cox, Christopher; Plesniak, Michael W.

2017-11-01

One of the most physiologically relevant factors within the cardiovascular system is the wall shear stress. The wall shear stress affects endothelial cells via mechanotransduction and atherosclerotic regions are strongly correlated with curvature and branching in the human vasculature, where the shear stress is both oscillatory and multidirectional. Also, the combined effect of curvature and pulsatility in cardiovascular flows produces unsteady vortices. In this work, our goal is to assess the correlation between multiple vortex pairs and wall shear stress. To accomplish this, we use an in-house high-order flux reconstruction Navier-Stokes solver to simulate pulsatile flow of a Newtonian blood-analog fluid through a rigid 180° curved artery model. We use a physiologically relevant flow rate and generate results using both fully developed and uniform entrance conditions, the latter motivated by the fact that flow upstream to a curved artery may not be fully developed. Under these two inflow conditions, we characterize the evolution of various vortex pairs and their subsequent effect on several wall shear stress metrics. Supported by GW Center for Biomimetics and Bioinspired Engineering.

Biological pacemaker created by minimally invasive somatic reprogramming in pigs with complete heart block

PubMed Central

Hu, Yu-Feng; Dawkins, James Frederick; Cho, Hee Cheol; Marbán, Eduardo; Cingolani, Eugenio

2016-01-01

Somatic reprogramming by reexpression of the embryonic transcription factor T-box 18 (TBX18) converts cardiomyocytes into pacemaker cells. We hypothesized that this could be a viable therapeutic avenue for pacemaker-dependent patients afflicted with device-related complications, and therefore tested whether adenoviral TBX18 gene transfer could create biological pacemaker activity in vivo in a large-animal model of complete heart block. Biological pacemaker activity, originating from the intramyocardial injection site, was evident in TBX18-transduced animals starting at day 2 and persisted for the duration of the study (14 days) with minimal backup electronic pacemaker use. Relative to controls transduced with a reporter gene, TBX18-transduced animals exhibited enhanced autonomic responses and physiologically superior chronotropic support of physical activity. Induced sinoatrial node cells could be identified by their distinctive morphology at the site of injection in TBX18-transduced animals, but not in controls. No local or systemic safety concerns arose. Thus, minimally invasive TBX18 gene transfer creates physiologically relevant pacemaker activity in complete heart block, providing evidence for therapeutic somatic reprogramming in a clinically relevant disease model. PMID:25031269

Alanyl-glutamine dipeptide restores the cytoprotective stress proteome of mesothelial cells exposed to peritoneal dialysis fluids.

PubMed

Kratochwill, Klaus; Boehm, Michael; Herzog, Rebecca; Lichtenauer, Anton Michael; Salzer, Elisabeth; Lechner, Michael; Kuster, Lilian; Bergmeister, Konstantin; Rizzi, Andreas; Mayer, Bernd; Aufricht, Christoph

2012-03-01

Exposure of mesothelial cells to peritoneal dialysis fluids (PDF) results in cytoprotective cellular stress responses (CSR) that counteract PDF-induced damage. In this study, we tested the hypothesis that the CSR may be inadequate in relevant models of peritoneal dialysis (PD) due to insufficient levels of glutamine, resulting in increased vulnerability against PDF cytotoxicity. We particularly investigated the role of alanyl-glutamine (Ala-Gln) dipeptide on the cytoprotective PDF stress proteome. Adequacy of CSR was investigated in two human in vitro models (immortalized cell line MeT-5A and mesothelial cells derived from peritoneal effluent of uraemic patients) following exposure to heat-sterilized glucose-based PDF (PD4-Dianeal, Baxter) diluted with medium and, in a comparative proteomics approach, at different levels of glutamine ranging from depletion (0 mM) via physiological (0.7 mM) to pharmacological levels (8 mM administered as Ala-Gln). Despite severe cellular injury, expression of cytoprotective proteins was dampened upon PDF exposure at physiological glutamine levels, indicating an inadequate CSR. Depletion of glutamine aggravated cell injury and further reduced the CSR, whereas addition of Ala-Gln at pharmacological level restored an adequate CSR, decreasing cellular damage in both PDF exposure systems. Ala-Gln specifically stimulated chaperoning activity, and cytoprotective processes were markedly enhanced in the PDF stress proteome. Taken together, this study demonstrates an inadequate CSR of mesothelial cells following PDF exposure associated with low and physiological levels of glutamine, indicating a new and potentially relevant pathomechanism. Supplementation of PDF with pharmacological doses of Ala-Gln restored the cytoprotective stress proteome, resulting in improved resistance of mesothelial cells to exposure to PDF. Future work will study the clinical relevance of CSR-mediated cytoprotection.

PPDB - A tool for investigation of plants physiology based on gene ontology.

PubMed

Sharma, Ajay Shiv; Gupta, Hari Om; Prasad, Rajendra

2014-09-02

Representing the way forward, from functional genomics and its ontology to functional understanding and physiological model, in a computationally tractable fashion is one of the ongoing challenges faced by computational biology. To tackle the standpoint, we herein feature the applications of contemporary database management to the development of PPDB, a searching and browsing tool for the Plants Physiology Database that is based upon the mining of a large amount of gene ontology data currently available. The working principles and search options associated with the PPDB are publicly available and freely accessible on-line ( http://www.iitr.ernet.in/ajayshiv/ ) through a user friendly environment generated by means of Drupal-6.24. By knowing that genes are expressed in temporally and spatially characteristic patterns and that their functionally distinct products often reside in specific cellular compartments and may be part of one or more multi-component complexes, this sort of work is intended to be relevant for investigating the functional relationships of gene products at a system level and, thus, helps us approach to the full physiology.

PPDB: A Tool for Investigation of Plants Physiology Based on Gene Ontology.

PubMed

Sharma, Ajay Shiv; Gupta, Hari Om; Prasad, Rajendra

2015-09-01

Representing the way forward, from functional genomics and its ontology to functional understanding and physiological model, in a computationally tractable fashion is one of the ongoing challenges faced by computational biology. To tackle the standpoint, we herein feature the applications of contemporary database management to the development of PPDB, a searching and browsing tool for the Plants Physiology Database that is based upon the mining of a large amount of gene ontology data currently available. The working principles and search options associated with the PPDB are publicly available and freely accessible online ( http://www.iitr.ac.in/ajayshiv/ ) through a user-friendly environment generated by means of Drupal-6.24. By knowing that genes are expressed in temporally and spatially characteristic patterns and that their functionally distinct products often reside in specific cellular compartments and may be part of one or more multicomponent complexes, this sort of work is intended to be relevant for investigating the functional relationships of gene products at a system level and, thus, helps us approach to the full physiology.

Women and Women's Issues in Industrial and Physiological Psychology.

ERIC Educational Resources Information Center

Knight, Patrick A.; And Others

In the area of industrial/organizational (I/O) psychology and physiological psychology, issues of gender have only begun to be addressed. An examination of the recent literatures in I/O and physiological psychology was undertaken to document the extent to which women are used as research subjects, to determine whether or not research relevant to…

Medical student attitudes toward kidney physiology and nephrology: a qualitative study.

PubMed

Roberts, John K; Sparks, Matthew A; Lehrich, Ruediger W

2016-11-01

Interest in nephrology among trainees is waning in the USA. Early perceptions and attitudes to subject matter can be linked to the quality of pre-clinical curricula. We wanted to explore these attitudes in the setting of modern curriculum redesign. We utilized Q methodology to understand first-year medical student attitudes after an innovative kidney physiology curriculum redesign that focuses on blending multiple learning methods. First-year medical students were invited to take a Q sort survey at the conclusion of a kidney physiology course. Students prioritized statements related to their understanding of kidney physiology, learning preferences, preferred course characteristics, perceived clinical relevance of kidney physiology, and interest in nephrology as a career. Factor analysis was performed to identify different student viewpoints. At the conclusion of our modified course, all students (n = 108) were invited to take the survey and 44 (41%) Q sorts were returned. Two dominant viewpoints were defined according to interest in nephrology. The Potentials are students who understand kidney physiology, perceive kidney physiology as clinically relevant, attend class sessions, utilize videos, and are willing to shadow a nephrologist. The Uninterested are students who are less satisfied with their kidney physiology knowledge, prefer to study alone with a textbook, avoid lectures, and are not interested in learning about nephrology. In an updated renal physiology course, students that use multiple learning methods also have favorable attitudes toward learning kidney physiology. Thus, modern curriculum changes that accommodate a variety of learning styles may promote positive attitudes toward nephrology.

Coordinated three-dimensional motion of the head and torso by dynamic neural networks.

PubMed

Kim, J; Hemami, H

1998-01-01

The problem of trajectory tracking control of a three dimensional (3D) model of the human upper torso and head is considered. The torso and the head are modeled as two rigid bodies connected at one point, and the Newton-Euler method is used to derive the nonlinear differential equations that govern the motion of the system. The two-link system is driven by six pairs of muscle like actuators that possess physiologically inspired alpha like and gamma like inputs, and spindle like and Golgi tendon organ like outputs. These outputs are utilized as reflex feedback for stability and stiffness control, in a long loop feedback for the purpose of estimating the state of the system (somesthesis), and as part of the input to the controller. Ideal delays of different duration are included in the feedforward and feedback paths of the system to emulate such delays encountered in physiological systems. Dynamical neural networks are trained to learn effective control of the desired maneuvers of the system. The feasibility of the controller is demonstrated by computer simulation of the successful execution of the desired maneuvers. This work demonstrates the capabilities of neural circuits in controlling highly nonlinear systems with multidelays in their feedforward and feedback paths. The ultimate long range goal of this research is toward understanding the working of the central nervous system in controlling movement. It is an interdisciplinary effort relying on mechanics, biomechanics, neuroscience, system theory, physiology and anatomy, and its short range relevance to rehabilitation must be noted.

Proposal for research and education: joint lectures and practicals on central nervous system anatomy and physiology.

PubMed

Kageyama, Ikuo; Yoshimura, Ken; Satoh, Yoshihide; Nanayakkara, Chinthani D; Pallegama, Ranjith W; Iwasaki, Shin-Ichi

2016-07-01

We coordinated anatomy and physiology lectures and practicals to facilitate an integrated understanding of morphology and function in a basic medical science program for dental students and to reduce the time spent on basic science education. This method is a means to provide the essential information and skills in less time. The overall impression was that the practice of joint central nervous system lectures and practicals was an efficient method for students, which suggests that joint lectures might also be useful for clinical subjects. About two-thirds of students felt that the joint anatomy and physiology lecture on the central nervous system was useful and necessary in understanding the relationship between morphology and function, at least for this subject. One-third of students were neutral on the effectiveness of this method. However, the survey results suggest that improvements are needed in the method and timing of joint lectures and practicals. The present teaching approach can be further improved by conducting combined lectures in which the form and function of anatomic structures are presented by the relevant departments during the same lecture. Finally, joint lecturers and practicals offer an opportunity to increase student understanding of the importance of new research findings by the present authors and other researchers.

Dynamic analysis of CO₂ labeling and cell respiration using membrane-inlet mass spectrometry.

PubMed

Yang, Tae Hoon

2014-01-01

Here, we introduce a mass spectrometry-based analytical method and relevant technical details for dynamic cell respiration and CO2 labeling analysis. Such measurements can be utilized as additional information and constraints for model-based (13)C metabolic flux analysis. Dissolved dynamics of oxygen consumption and CO2 mass isotopomer evolution from (13)C-labeled tracer substrates through different cellular processes can be precisely measured on-line using a miniaturized reactor system equipped with a membrane-inlet mass spectrometer. The corresponding specific rates of physiologically relevant gases and CO2 mass isotopomers can be quantified within a short-term range based on the liquid-phase dynamics of dissolved fermentation gases.

Do infants find snakes aversive? Infants' physiological responses to "fear-relevant" stimuli.

PubMed

Thrasher, Cat; LoBue, Vanessa

2016-02-01

In the current research, we sought to measure infants' physiological responses to snakes-one of the world's most widely feared stimuli-to examine whether they find snakes aversive or merely attention grabbing. Using a similar method to DeLoache and LoBue (Developmental Science, 2009, Vol. 12, pp. 201-207), 6- to 9-month-olds watched a series of multimodal (both auditory and visual) stimuli: a video of a snake (fear-relevant) or an elephant (non-fear-relevant) paired with either a fearful or happy auditory track. We measured physiological responses to the pairs of stimuli, including startle magnitude, latency to startle, and heart rate. Results suggest that snakes capture infants' attention; infants showed the fastest startle responses and lowest average heart rate to the snakes, especially when paired with a fearful voice. Unexpectedly, they also showed significantly reduced startle magnitude during this same snake video plus fearful voice combination. The results are discussed with respect to theoretical perspectives on fear acquisition. Copyright © 2015 Elsevier Inc. All rights reserved.

Binding of trivalent chromium to serum transferrin is sufficiently rapid to be physiologically relevant.

PubMed

Deng, Ge; Wu, Kristi; Cruce, Alex A; Bowman, Michael K; Vincent, John B

2015-02-01

Transferrin, the major iron transport protein in the blood, also transports trivalent chromium in vivo. Recent in vitro studies have, however, suggested that the binding of chromic ions to apotransferrin is too slow to be biologically relevant. Nevertheless, the in vitro studies have generally failed to adequately take physiological bicarbonate concentrations into account. In aqueous buffer (with ambient (bi)carbonate concentrations), the binding of chromium to transferrin is too slow to be physiologically relevant, taking days to reach equilibrium with the protein's associated conformational changes. However, in the presence of 25mM (bi)carbonate, the concentration in human blood, chromic ions bind rapidly and tightly to transferrin. Details of the kinetics of chromium binding to human serum transferrin and conalbumin (egg white transferrin) in the presence of bicarbonate and other major potential chromium ligands are described and are consistent with transferrin being the major chromic ion transporter from the blood to tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

The cardiovascular system after exercise

PubMed Central

Romero, Steven A.; Minson, Christopher T.

2017-01-01

Recovery from exercise refers to the time period between the end of a bout of exercise and the subsequent return to a resting or recovered state. It also refers to specific physiological processes or states occurring after exercise that are distinct from the physiology of either the exercising or the resting states. In this context, recovery of the cardiovascular system after exercise occurs across a period of minutes to hours, during which many characteristics of the system, even how it is controlled, change over time. Some of these changes may be necessary for long-term adaptation to exercise training, yet some can lead to cardiovascular instability during recovery. Furthermore, some of these changes may provide insight into when the cardiovascular system has recovered from prior training and is physiologically ready for additional training stress. This review focuses on the most consistently observed hemodynamic adjustments and the underlying causes that drive cardiovascular recovery and will highlight how they differ following resistance and aerobic exercise. Primary emphasis will be placed on the hypotensive effect of aerobic and resistance exercise and associated mechanisms that have clinical relevance, but if left unchecked, can progress to symptomatic hypotension and syncope. Finally, we focus on the practical application of this information to strategies to maximize the benefits of cardiovascular recovery, or minimize the vulnerabilities of this state. We will explore appropriate field measures, and discuss to what extent these can guide an athlete’s training. PMID:28153943

Oral Exposure and Absorption of Toxicants

EPA Science Inventory

This chapter provides an overview of the toxicokinetics of orally absorbed xenobiotics. This includes a description of the basic anatomy and physiology of the digestive tract most relevant to the absorption process. In addition, differences in anatomy and physiology between human...

Physiology of Penile Erection—A Brief History of the Scientific Understanding up till the Eighties of the 20th Century

PubMed Central

2015-01-01

Abstract Introduction Understanding the physiology of penile erection is important for all who work in the field of sexual medicine. Aim The aim of this study was to highlight and analyze historical aspects of the scientific understanding of penile erection. Methods (i) Review of the chapters on the physiology of erection out of the author's collection of books dealing with male sexual functioning published in the German, French, Dutch, and English language in between 1780 and 1940. (ii) Review of the topic “physiology of penile erection” of relevant chapters of C lassical writings on erectile dysfunction. A n annotated collection of original texts from three millennia, including the study of all relevant references mentioned in these books. Main Outcome Measure The main outcome measure used for the study was the scientific understanding of the physiology of penile erection. Results In Antiquity, Galen considered penile erection as the result the accumulation of air. His ideas so dominated medieval medicine that nearly everyone then alive was a Galenist. The beginning of the Renaissance shows meaningful examples of experimental scientific work on the penis. Da Vinci correctly concluded that erections were caused by blood, and in the 18th century, Von Haller from Switzerland was the first who explained that erections were under the control of the nervous system. In the 19th century, a mindset that emphasized on experimentation determined a new direction, namely experimental physiology. Animal studies clarified that stimulation of the nervi erigentes‐induced small muscle relaxation in the corpora cavernosa. Nearly all were published in the German language. That may be one of the reasons that the existence of the concept of smooth muscle relaxation remained controversial until the first World Congress on Impotence in 1984 in Paris. Conclusions As the Renaissance's innovative research defined neural and vascular physiologic phenomena responsible for penile erection. The concepts from animal experimentations in Europe in the 19th century significantly contributed to the current understanding of penile erection. van Driel MF. Physiology of penile erection—a brief history of the scientific understanding up till the eighties of the 20th century. Sex Med 2015;3:343–351. PMID:26797073

"Thinking ethics": a novel, pilot, proof-of-concept program of integrating ethics into the Physiology curriculum in South India.

PubMed

D, Savitha; Vaz, Manjulika; Vaz, Mario

2017-06-01

Integrating medical ethics into the physiology teaching-learning program has been largely unexplored in India. The objective of this exercise was to introduce an interactive and integrated ethics program into the Physiology course of first-year medical students and to evaluate their perceptions. Sixty medical students (30 men, 30 women) underwent 11 sessions over a 7-mo period. Two of the Physiology faculty conducted these sessions (20-30 min each) during the routine physiology (theory/practicals) classes that were of shorter duration and could, therefore, accommodate the discussion of related ethical issues. This exercise was in addition to the separate ethics classes conducted by the Medical Ethics department. The sessions were open ended, student centered, and designed to stimulate critical thinking. The students' perceptions were obtained through a semistructured questionnaire and focused group discussions. The students found the program unique, thought provoking, fully integrated, and relevant. It seldom interfered with the physiology teaching. They felt that the program sensitized them about ethical issues and prepared them for their clinical years, to be "ethical doctors." Neutral observers who evaluated each session felt that the integrated program was relevant to the preclinical year and that the program was appropriate in its content, delivery, and student involvement. An ethics course taught in integration with Physiology curriculum was found to be beneficial, feasible, and compatible with Physiology by students as well as neutral observers. Copyright © 2017 the American Physiological Society.

Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology

PubMed Central

de Graaf, Albert A.; Freidig, Andreas P.; De Roos, Baukje; Jamshidi, Neema; Heinemann, Matthias; Rullmann, Johan A.C.; Hall, Kevin D.; Adiels, Martin; van Ommen, Ben

2009-01-01

The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a “middle-out” strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from “-omics” signatures are identified as key elements of a successful systems biology modeling approach in nutrition research—one that integrates physiological mechanisms and data at multiple space and time scales. PMID:19956660

The Cajal school and the physiological role of astrocytes: a way of thinking

PubMed Central

Navarrete, Marta; Araque, Alfonso

2014-01-01

Cajal is widely recognized by the scientific community for his important contributions to our knowledge of the neuronal organization of the nervous system. His studies on neuroglial cells are less recognized, yet they are no less relevant to our current understanding of the cellular bases of brain structure. Two pioneering studies published a century ago –“Something about the physiological significance of neuroglia” (Ramón y Cajal, 1897) and “A contribution to the understanding of neuroglia in the human brain” (Ramón y Cajal, 1913)—focused on glial cells and their role in brain physiology. Novel findings obtained using state-of-the-art and sophisticated technologies largely confirm many of the groundbreaking hypotheses proposed by Cajal related to the structural-functional properties of neuroglia. Here we propose to the reader a journey guided by the ideas of Cajal through the recent findings on the functional significance of astrocytes, the most abundant neuroglial cell type in the nervous system. Astrocyte–neuron interaction, which represents an emerging field in current neuroscience with important implications for our understanding of the cellular processes underlying brain function, has its roots in many of the original concepts proposed by Cajal. PMID:24904302

Forebrain networks and the control of feeding by environmental learned cues

PubMed Central

Petrovich, Gorica D.

2013-01-01

The motivation to eat is driven by a complex sum of physiological and non-physiological influences computed by the brain. Physiological signals that inform the brain about energy and nutrient needs are the primary drivers, but environmental signals unrelated to energy balance also control appetite and eating. The two components could act in concert to support the homeostatic regulation of food intake. Often, however, environmental influences rival physiological control and stimulate eating irrespective of satiety, or inhibit eating irrespective of hunger. If persistent, such maladaptive challenges to the physiological system could lead to dysregulated eating and ultimately to eating disorders. Nevertheless, the brain mechanisms underlying environmental contribution in the control of food intake are poorly understood. This paper provides an overview in recent advances in deciphering the critical brain systems using rodent models for environmental control by learned cues. These models use associative learning to compete with the physiological control, and in one preparation food cues stimulate a meal despite satiety, while in another preparation fear cues stop a meal despite hunger. Thus far, four forebrain regions have been identified as part of the essential cue induced feeding circuitry. These are telencephalic areas critical for associative learning, memory encoding, and decision making, the amygdala, hippocampus and prefrontal cortex and the lateral hypothalamus, which functions to integrate feeding, reward, and motivation. This circuitry also engages two orexigenic peptides, ghrelin and orexin. A parallel amygdalar circuitry supports fear cue cessation of feeding. These findings illuminate the brain mechanisms underlying environmental control of food intake and might be also relevant to aspects of human appetite and maladaptive overeating and undereating. PMID:23562305

Relevance of human anatomy in daily clinical practice.

PubMed

Arráez-Aybar, Luis-Alfonso; Sánchez-Montesinos, Indalecio; Mirapeix, Rosa-M; Mompeo-Corredera, Blanca; Sañudo-Tejero, Jose-Ramón

2010-12-20

the aim of this study has been to evaluate the relevance of gross human anatomy in daily clinical practice and to compare it to that of other basic sciences (biochemistry, bioethics, cytohistology, microbiology, pharmacology, physiology, psychology). a total of 1250 questionnaires were distributed among 38 different medical speciality professionals. Answers were analyzed taking into account speciality (medical, surgery and others), professional status (training physician or staff member) and professional experience. the response rate was 42.9% (n=536). Gross human anatomy was considered the most relevant basic discipline for surgical specialists, while pharmacology and physiology were most relevant for medical specialists. Knowledge of anatomy was also considered fundamental for understanding neurological or musculoskeletal disorders. In undergraduate programmes, the most important focuses in teaching anatomy were radiological, topographical and functional anatomy followed by systematic anatomy. In daily medical practice anatomy was considered basic for physical examination, symptom interpretation and interpretation of radiological images. When professional status or professional experience was considered, small variations were shown and there were no significant differences related to gender or community. our results underline the relevance of basic sciences (gross anatomy, physiology, and pharmacology) in daily professional activity. Evidence-based studies such as ours, lend greater credibility and objectivity to the role of gross anatomy in the undergraduate training of health professionals and should help to establish a more appropriate curriculum for future professionals. 2010 Elsevier GmbH. All rights reserved.

Role of innate and drug-induced dysregulation of brain stress and arousal systems in addiction: Focus on corticotropin-releasing factor, nociceptin/orphanin FQ, and orexin/hypocretin

PubMed Central

Martin-Fardon, Rémi; Zorrilla, Eric P.; Ciccocioppo, Roberto; Weiss, Friedbert

2010-01-01

Stress-like symptoms are an integral part of acute and protracted drug withdrawal, and several lines of evidence have shown that dysregulation of brain stress systems, including the extrahypothalamic corticotropin-releasing factor (CRF) system, following long-term drug use is of major importance in maintaining drug and alcohol addiction. Recently, two other neuropeptide systems have attracted interest, the nociceptin/orphanin FQ (N/OFQ) and orexin/hypocretin (Orx/Hcrt) systems. N/OFQ participates in a wide range of physiological responses, and the hypothalamic Orx/Hcrt system helps regulate several physiological processes, including feeding, energy metabolism, and arousal. Moreover, these two systems have been suggested to participate in psychiatric disorders, including anxiety and drug addiction. Dysregulation of these systems by chronic drug exposure has been hypothesized to play a role in the maintenance of addiction and dependence. Recent evidence demonstrated that interactions between CRF-N/OFQ and CRF-Orx/Hcrt systems may be functionally relevant for the control of stress-related addictive behavior. The present review discusses recent findings that support the hypotheses of the participation and dysregulation of these systems in drug addiction and evaluates the current understanding of interactions among these stress-regulatory peptides. PMID:20026088

In vitro microfluidic circulatory system for circulating cancer cells

PubMed Central

wan, jiandi; Fan, Rong; Emery, Travis; Zhang, Yongguo; Xia, Yuxuan; Sun, Jun; Wan, Jiandi

2016-01-01

Circulating tumor cells (CTCs) experience hemodynamic shear stress in circulation and play critical roles in cancer metastasis. The effect of shear on CTCs, however, remains less studied. Here, we described a protocol to circulate HCT116 human colon cancer cells in a microfluidic circulatory system mimicking physiologically relevant circulating conditions. This protocol represents a useful scaffold to mimic the transportation of CTCs in circulation and thus provides an effective means to study the effect of shear on CTCs. We anticipate that future studies using the developed system will help us to further investigate the regulatory roles of shear in molecular responses of CTCs. PMID:28690779

Exploring the Limits of Cell Adhesion under Shear Stress within Physiological Conditions and beyond on a Chip.

PubMed

Stamp, Melanie E M; Jötten, Anna M; Kudella, Patrick W; Breyer, Dominik; Strobl, Florian G; Geislinger, Thomas M; Wixforth, Achim; Westerhausen, Christoph

2016-10-21

Cell adhesion processes are of ubiquitous importance for biomedical applications such as optimization of implant materials. Here, not only physiological conditions such as temperature or pH, but also topographical structures play crucial roles, as inflammatory reactions after surgery can diminish osseointegration. In this study, we systematically investigate cell adhesion under static, dynamic and physiologically relevant conditions employing a lab-on-a-chip system. We screen adhesion of the bone osteosarcoma cell line SaOs-2 on a titanium implant material for pH and temperature values in the physiological range and beyond, to explore the limits of cell adhesion, e.g., for feverish and acidic conditions. A detailed study of different surface roughness R q gives insight into the correlation between the cells' abilities to adhere and withstand shear flow and the topography of the substrates, finding a local optimum at R q = 22 nm. We use shear stress induced by acoustic streaming to determine a measure for the ability of cell adhesion under an external force for various conditions. We find an optimum of cell adhesion for T = 37 °C and pH = 7.4 with decreasing cell adhesion outside the physiological range, especially for high T and low pH. We find constant detachment rates in the physiological regime, but this behavior tends to collapse at the limits of 41 °C and pH 4.

Ghrelin

PubMed Central

Wu, James T.; Kral, John G.

2004-01-01

Objective: Ghrelin is a novel gastric hormone recognized in 1999 as a mediator of growth hormone release. Since growth hormone is anabolic, an important function of ghrelin may be to coordinate energy needs with the growth process. Newly discovered biologic roles of ghrelin imply that it may have other important physiological functions as well. This is a review of recent clinically relevant, yet less well-known, physiologic actions of ghrelin. Summary Background Data: Ghrelin has profound orexigenic, adipogenic, and somatotrophic properties, increasing food intake and body weight. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue receptor in the pituitary gland, thus fulfilling criteria of a brain-gut peptide. The brain-gut axis is the effector of anabolism by regulating growth, feeding, and metabolism via vagal afferents mediating ghrelin signaling. However, the wide tissue distribution of ghrelin suggests that it may have other functions as well. Methods: Systematic literature review of all PubMed citations between 1999 and August 2003 focusing on clinically relevant biochemical and physiological characteristics of ghrelin. Results: Ghrelin is an important component of an integrated regulatory system of growth and metabolism acting via the vagus nerve, and is implicated in a variety of altered energy states such as obesity, eating disorders, neoplasia, and cachexia. It also enhances immune responses and potentially down-regulates anti-inflammatory molecules. Ghrelin's role as a brain-gut peptide emphasizes the significance of afferent vagal fibers as a major pathway to the brain, serving the purpose of maintaining physiologic homeostasis. Conclusions: The discovery of ghrelin has increased our understanding of feeding regulation, nutritional homeostasis, and metabolic processes. Further characterization of ghrelin's functions will likely generate new pharmacological approaches to diagnose and treat different disease entities including those related to the over-nutrition of obesity and the catabolic response to surgical trauma. PMID:15024307

Exposure of ova to cortisol pre-fertilisation affects subsequent behaviour and physiology of brown trout.

PubMed

Sloman, Katherine A

2010-08-01

Even before fertilisation, exposure of ova to high levels of stress corticosteroids can have significant effects on offspring in a variety of animals. In fish, high levels of cortisol in ovarian fluid can elicit morphological changes and reduce offspring survival. Whether there are other more subtle effects, including behavioural effects, of exposure to cortisol pre-fertilisation in fish is unclear. Here I demonstrate that a brief (3h) exposure of brown trout eggs to a physiologically relevant ( approximately 500 microg l(-)(1)) concentration of cortisol pre-fertilisation resulted in changes to developing offspring. Embryos exposed to cortisol pre-fertilisation displayed elevated oxygen consumption and ammonia excretion rates during development. After hatch, in contrast to the effects of cortisol exposure in juvenile fish, fish exposed to cortisol as eggs were more aggressive than control individuals and responded differently within a maze system. Thus, a transient exposure to corticosteroids in unfertilised eggs results in both physiological and behavioural alterations in fish. Copyright 2010 Elsevier Inc. All rights reserved.

Towards the virtual artery: a multiscale model for vascular physiology at the physics-chemistry-biology interface.

PubMed

Hoekstra, Alfons G; Alowayyed, Saad; Lorenz, Eric; Melnikova, Natalia; Mountrakis, Lampros; van Rooij, Britt; Svitenkov, Andrew; Závodszky, Gábor; Zun, Pavel

2016-11-13

This discussion paper introduces the concept of the Virtual Artery as a multiscale model for arterial physiology and pathologies at the physics-chemistry-biology (PCB) interface. The cellular level is identified as the mesoscopic level, and we argue that by coupling cell-based models with other relevant models on the macro- and microscale, a versatile model of arterial health and disease can be composed. We review the necessary ingredients, both models of arteries at many different scales, as well as generic methods to compose multiscale models. Next, we discuss how this can be combined into the virtual artery. Finally, we argue that the concept of models at the PCB interface could or perhaps should become a powerful paradigm, not only as in our case for studying physiology, but also for many other systems that have such PCB interfaces.This article is part of the themed issue 'Multiscale modelling at the physics-chemistry-biology interface'. © 2016 The Authors.

Efficient solvers for coupled models in respiratory mechanics.

PubMed

Verdugo, Francesc; Roth, Christian J; Yoshihara, Lena; Wall, Wolfgang A

2017-02-01

We present efficient preconditioners for one of the most physiologically relevant pulmonary models currently available. Our underlying motivation is to enable the efficient simulation of such a lung model on high-performance computing platforms in order to assess mechanical ventilation strategies and contributing to design more protective patient-specific ventilation treatments. The system of linear equations to be solved using the proposed preconditioners is essentially the monolithic system arising in fluid-structure interaction (FSI) extended by additional algebraic constraints. The introduction of these constraints leads to a saddle point problem that cannot be solved with usual FSI preconditioners available in the literature. The key ingredient in this work is to use the idea of the semi-implicit method for pressure-linked equations (SIMPLE) for getting rid of the saddle point structure, resulting in a standard FSI problem that can be treated with available techniques. The numerical examples show that the resulting preconditioners approach the optimal performance of multigrid methods, even though the lung model is a complex multiphysics problem. Moreover, the preconditioners are robust enough to deal with physiologically relevant simulations involving complex real-world patient-specific lung geometries. The same approach is applicable to other challenging biomedical applications where coupling between flow and tissue deformations is modeled with additional algebraic constraints. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

A construct-network approach to bridging diagnostic and physiological domains: application to assessment of externalizing psychopathology.

PubMed

Patrick, Christopher J; Venables, Noah C; Yancey, James R; Hicks, Brian M; Nelson, Lindsay D; Kramer, Mark D

2013-08-01

A crucial challenge in efforts to link psychological disorders to neural systems, with the aim of developing biologically informed conceptions of such disorders, is the problem of method variance (Campbell & Fiske, 1959). Since even measures of the same construct in differing domains correlate only moderately, it is unsurprising that large sample studies of diagnostic biomarkers yield only modest associations. To address this challenge, a construct-network approach is proposed in which psychometric operationalizations of key neurobehavioral constructs serve as anchors for identifying neural indicators of psychopathology-relevant dispositions, and as vehicles for bridging between domains of clinical problems and neurophysiology. An empirical illustration is provided for the construct of inhibition-disinhibition, which is of central relevance to problems entailing deficient impulse control. Findings demonstrate that: (1) a well-designed psychometric index of trait disinhibition effectively predicts externalizing problems of multiple types, (2) this psychometric measure of disinhibition shows reliable brain response correlates, and (3) psychometric and brain-response indicators can be combined to form a joint psychoneurometric factor that predicts effectively across clinical and physiological domains. As a methodology for bridging between clinical problems and neural systems, the construct-network approach provides a concrete means by which existing conceptions of psychological disorders can accommodate and be reshaped by neurobiological insights. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Neuromodulators: available agents, physiology, and anatomy.

PubMed

Nettar, Kartik; Maas, Corey

2011-12-01

Neuromodulators have risen to the forefront of aesthetic medicine. By reversibly relaxing target muscles, neuromodulators exhibit their effect by softening hyperfunctional lines. An understanding of their physiology, relevant facial anatomy, and current agents is imperative for a successful aesthetic practice. © Thieme Medical Publishers.

In vitro microfluidic models of tumor microenvironment to screen transport of drugs and nanoparticles.

PubMed

Ozcelikkale, Altug; Moon, Hye-Ran; Linnes, Michael; Han, Bumsoo

2017-09-01

Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine. Microfluidics offer significant advantages over traditional macroscale cell cultures by enabling recapitulation of tumor microenvironment through precise control of physiological cues such as hydrostatic pressure, shear stress, oxygen, and nutrient gradients. Microfluidic systems have recently started to be adapted for screening of drugs and NPs under physiologically relevant settings. So far the two primary application areas of microfluidics in this area have been high-throughput screening using traditional culture settings such as single cells or multicellular tumor spheroids, and mimicry of tumor microenvironment for study of cancer-related cell-cell and cell-matrix interactions. These microfluidic technologies are also useful in modeling specific steps in NP delivery to tumor and characterize NP transport properties and outcomes by systematic variation of physiological conditions. Ultimately, it will be possible to design drug-screening platforms uniquely tailored for individual patient physiology using microfluidics. These in vitro models can contribute to development of precision medicine by enabling rapid and patient-specific evaluation of cancer nanomedicine. WIREs Nanomed Nanobiotechnol 2017, 9:e1460. doi: 10.1002/wnan.1460 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Three-dimensional cell culture models for investigating human viruses.

PubMed

He, Bing; Chen, Guomin; Zeng, Yi

2016-10-01

Three-dimensional (3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover, these models bridge the gap between traditional two-dimensional (2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition, 3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.

Treadmill Exercise Within LBNP as an Integrated Coutermeasure to Microgravity

NASA Technical Reports Server (NTRS)

Lee, Stuart; Hargens, A. R.; Schneider, S. M.; Watenpaugh, D. E.

2010-01-01

An integrated exercise countermeasure for microgravity is needed to protect multiple physiologic systems and save crew time. Such a countermeasure should protect orthostatic tolerance, upright ambulatory capability (including sprinting), aerobic capacity, muscle strength/endurance, and other physiologic parameters relevant to human performance. We developed a novel physiologic countermeasure, treadmill exercise within LBNP, for preventing cardiovascular and musculoskeletal deconditioning associated with prolonged bed rest and spaceflight. We evaluated 40 min of daily LBNP treadmill exercise by a battery of physiologic parameters relevant to maintaining exercise performance and health of both women and men during bed-rest (simulated microgravity) studies lasting from 5 to 60 days. For 30 day studies, we employed identical twins with one twin as the control and the other twin as the exerciser to improve comparative power. During the WISE 60-day HDT study, the treadmill exercise within LBNP was performed 3-4 days each week and resistive exercise was performed 2-3 days each week. Our treadmill within LBNP protocol maintained plasma volume and sprint speed (30 day HDT bed-rest studies of identical twins), orthostatic tolerance to a degree, upright exercise capacity, muscle strength and endurance, and some bone parameters during 30 day (twin studies) and 60 day (WISE-2005) bed-rest simulations of microgravity. When combining treadmill exercise within LBNP and resistive exercise (WISE), cardiac mass increased significantly in the exercise (EX) group during bed rest relative to controls (CON). Upright peak VO2, and knee extensor strength and endurance decreased significantly in CON subjects; but these parameters were preserved in the EX group. In the 60 day WISE study, each LBNP exercise session was followed immediately by 10 minutes of static LBNP, and the last such session occurred three days before the end of bed rest. Still, orthostatic tolerance was better maintained in the EX group than in the CON group. Therefore, these collective peer-reviewed results document that our treadmill exercise within LBNP countermeasure safely and efficiently protects multiple physiologic systems in women and men during bed-rest studies of up to 60 days. Supported by NASA grants NNJ04HF71G and NAG 9-1425, NIH grant GCRC M01 RR00827 and by WISE support from ESA, NASA, CSA, and CNES.

Multifunctional enzymes from reduced genomes - model proteins for simple primordial metabolism?

PubMed

Seelig, Burckhard

2017-08-01

Billions of years of evolution have yielded today's complex metabolic networks driven by efficient and highly specialized enzymes. In contrast, the metabolism of the earliest cellular life forms was likely much simpler with only a few enzymes of comparatively low activity. It has been speculated that these early enzymes had low specificities and in turn were able to perform multiple functions. In this issue of Molecular Microbiology, Ferla et al. describe examples of enzymes that catalyze chemically distinct reactions while using the same active site. Most importantly, the authors demonstrated that the comparatively weak activities of these multifunctional enzymes are each physiologically relevant. These findings contrast with simply promiscuous enzyme activities, which have been described numerous times but are not physiologically relevant. Ferla et al. elegantly combined initial bioinformatics searches for enzyme candidates with sound kinetic measurements, evolutionary considerations and even structural discussions. The phenomenon of multifunctionality appears to be a mechanism for bacteria with reduced genomes to compensate for their lack of certain enzymes. In the broader context of evolution, these organisms could be considered living model systems to study features of long-extinct early cellular life. © 2017 John Wiley & Sons Ltd.

The Constraints, Construction, and Verification of a Strain-Specific Physiologically Based Pharmacokinetic Rat Model.

PubMed

Musther, Helen; Harwood, Matthew D; Yang, Jiansong; Turner, David B; Rostami-Hodjegan, Amin; Jamei, Masoud

2017-09-01

The use of in vitro-in vivo extrapolation (IVIVE) techniques, mechanistically incorporated within physiologically based pharmacokinetic (PBPK) models, can harness in vitro drug data and enhance understanding of in vivo pharmacokinetics. This study's objective was to develop a user-friendly rat (250 g, male Sprague-Dawley) IVIVE-linked PBPK model. A 13-compartment PBPK model including mechanistic absorption models was developed, with required system data (anatomical, physiological, and relevant IVIVE scaling factors) collated from literature and analyzed. Overall, 178 system parameter values for the model are provided. This study also highlights gaps in available system data required for strain-specific rat PBPK model development. The model's functionality and performance were assessed using previous literature-sourced in vitro properties for diazepam, metoprolol, and midazolam. The results of simulations were compared against observed pharmacokinetic rat data. Predicted and observed concentration profiles in 10 tissues for diazepam after a single intravenous (i.v.) dose making use of either observed i.v. clearance (CL iv ) or in vitro hepatocyte intrinsic clearance (CL int ) for simulations generally led to good predictions in various tissue compartments. Overall, all i.v. plasma concentration profiles were successfully predicted. However, there were challenges in predicting oral plasma concentration profiles for metoprolol and midazolam, and the potential reasons and according solutions are discussed. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Neurophysiology and neural engineering: a review.

PubMed

Prochazka, Arthur

2017-08-01

Neurophysiology is the branch of physiology concerned with understanding the function of neural systems. Neural engineering (also known as neuroengineering) is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, enhance, or otherwise exploit the properties and functions of neural systems. In most cases neural engineering involves the development of an interface between electronic devices and living neural tissue. This review describes the origins of neural engineering, the explosive development of methods and devices commencing in the late 1950s, and the present-day devices that have resulted. The barriers to interfacing electronic devices with living neural tissues are many and varied, and consequently there have been numerous stops and starts along the way. Representative examples are discussed. None of this could have happened without a basic understanding of the relevant neurophysiology. I also consider examples of how neural engineering is repaying the debt to basic neurophysiology with new knowledge and insight. Copyright © 2017 the American Physiological Society.

Battery-free, wireless sensors for full-body pressure and temperature mapping.

PubMed

Han, Seungyong; Kim, Jeonghyun; Won, Sang Min; Ma, Yinji; Kang, Daeshik; Xie, Zhaoqian; Lee, Kyu-Tae; Chung, Ha Uk; Banks, Anthony; Min, Seunghwan; Heo, Seung Yun; Davies, Charles R; Lee, Jung Woo; Lee, Chi-Hwan; Kim, Bong Hoon; Li, Kan; Zhou, Yadong; Wei, Chen; Feng, Xue; Huang, Yonggang; Rogers, John A

2018-04-04

Thin, soft, skin-like sensors capable of precise, continuous measurements of physiological health have broad potential relevance to clinical health care. Use of sensors distributed over a wide area for full-body, spatiotemporal mapping of physiological processes would be a considerable advance for this field. We introduce materials, device designs, wireless power delivery and communication strategies, and overall system architectures for skin-like, battery-free sensors of temperature and pressure that can be used across the entire body. Combined experimental and theoretical investigations of the sensor operation and the modes for wireless addressing define the key features of these systems. Studies with human subjects in clinical sleep laboratories and in adjustable hospital beds demonstrate functionality of the sensors, with potential implications for monitoring of circadian cycles and mitigating risks for pressure-induced skin ulcers. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A COMPREHENSIVE INSIGHT ON OCULAR PHARMACOKINETICS

PubMed Central

Agrahari, Vibhuti; Mandal, Abhirup; Agrahari, Vivek; Trinh, Hoang My; Joseph, Mary; Ray, Animikh; Hadji, Hicheme; Mitra, Ranjana; Pal, Dhananjay; Mitra, Ashim K.

2017-01-01

Eye is a distinctive organ with protective anatomy and physiology. Several pharmacokinetics compartment model of ocular drug delivery has been developed for describing the absorption, distribution and elimination of ocular drugs in the eye. Determining pharmacokinetics parameters in ocular tissues is a major challenge because of the complex anatomy and dynamic physiological barrier of the eye. In this review, pharmacokinetics of these compartments exploring different drugs, delivery systems and routes of administration are discussed including factors affecting intraocular bioavailability. Factors such as pre-corneal fluid drainage, drug binding to tear proteins, systemic drug absorption, corneal factors, melanin binding, drug metabolism renders ocular delivery challenging and elaborated in this manuscript. Several compartment models are discussed those are developed in ocular drug delivery to study the pharmacokinetics parameters. There are several transporters present in both anterior and posterior segments of the eye which play a significant role in ocular pharmacokinetics and summarized briefly. Moreover, several ocular pharmacokinetics animal models and relevant studies are reviewed and discussed in addition to the pharmacokinetics of various ocular formulations. PMID:27798766

Physiological profile of fighters influences training organisation in combat sports: response to Del Vecchio, Hirata, and Franchini (2011).

PubMed

Paillard, Thierry

2011-12-01

The article by Del Vecchio, et al. (2011) provides relevant information to trainers about the effort-pause ratio during mixed martial arts matches. Taking into account the physiological profiles of fighters would increase interest in these findings.

Travelling within the fetal gut: simple rules for an arduous journey

PubMed Central

2014-01-01

The complex physiology of the gastrointestinal tract is regulated by intricate neural networks embedded within the gut wall. How neural crest cells colonize the intestine to form the enteric nervous system is of great interest to developmental biologists, but also highly relevant for understanding gastrointestinal disorders. A recent paper in BMC Biology addresses this issue with live imaging of gut explants from mouse embryos. See research article: http://www.biomedcentral.com/1741-7007/12/23. PMID:25184534

TEDD Annual Meeting with 3D Bioprinting Workshop.

PubMed

Raghunath, Michael; Rimann, Markus; Kopanska, Katarzyna S; Laternser, Sandra

2018-02-01

Bioprinting is the technology of choice for realizing functional tissues such as vascular system, muscle, cartilage and bone. In the future, bioprinting will influence the way we engineer tissues and bring it to a new level of physiological relevance. That was the topic of the 2017 TEDD Annual Meeting at ZHAW Waedenswil on 8th and 9th November. In an exciting workshop, the two companies regenHU Ltd. and CELLINK gave us an insight into highly topical applications and collaborations in this domain.

A simple sensing mechanism for wireless, passive pressure sensors.

PubMed

Drazan, John F; Wassick, Michael T; Dahle, Reena; Beardslee, Luke A; Cady, Nathaniel C; Ledet, Eric H

2016-08-01

We have developed a simple wireless pressure sensor that consists of only three electrically isolated components. Two conductive spirals are separated by a closed cell foam that deforms when exposed to changing pressures. This deformation changes the capacitance and thus the resonant frequency of the sensors. Prototype sensors were submerged and wirelessly interrogated while being exposed to physiologically relevant pressures from 10 to 130 mmHg. Sensors consistently exhibited a sensitivity of 4.35 kHz/mmHg which is sufficient for resolving physiologically relevant pressure changes in vivo. These simple sensors have the potential for in vivo pressure sensing.

Physiological and Transcriptional Responses of Different Industrial Microbes at Near-Zero Specific Growth Rates.

PubMed

Ercan, Onur; Bisschops, Markus M M; Overkamp, Wout; Jørgensen, Thomas R; Ram, Arthur F; Smid, Eddy J; Pronk, Jack T; Kuipers, Oscar P; Daran-Lapujade, Pascale; Kleerebezem, Michiel

2015-09-01

The current knowledge of the physiology and gene expression of industrially relevant microorganisms is largely based on laboratory studies under conditions of rapid growth and high metabolic activity. However, in natural ecosystems and industrial processes, microbes frequently encounter severe calorie restriction. As a consequence, microbial growth rates in such settings can be extremely slow and even approach zero. Furthermore, uncoupling microbial growth from product formation, while cellular integrity and activity are maintained, offers perspectives that are economically highly interesting. Retentostat cultures have been employed to investigate microbial physiology at (near-)zero growth rates. This minireview compares information from recent physiological and gene expression studies on retentostat cultures of the industrially relevant microorganisms Lactobacillus plantarum, Lactococcus lactis, Bacillus subtilis, Saccharomyces cerevisiae, and Aspergillus niger. Shared responses of these organisms to (near-)zero growth rates include increased stress tolerance and a downregulation of genes involved in protein synthesis. Other adaptations, such as changes in morphology and (secondary) metabolite production, were species specific. This comparison underlines the industrial and scientific significance of further research on microbial (near-)zero growth physiology. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Controversial constitutive TSHR activity: patients, physiology, and in vitro characterization.

PubMed

Huth, S; Jaeschke, H; Schaarschmidt, J; Paschke, R

2014-06-01

G protein-coupled receptors constitute a large family of transmembrane receptors, which activate cellular responses by signal transmission and regulation of second messenger metabolism after ligand binding. For several of these receptors it is known that they also signal ligand-independently. The G protein-coupled thyroid stimulating hormone receptor (TSHR) is characterized by a high level of constitutive activity in the wild type state. However, little is known yet concerning the physiological relevance of the constitutive wild type TSHR activity. Certainly, knowledge of the physiological relevance of constitutive wild type receptor activity is necessary to better understand thyroid physiology and it is a prerequisite for the development of better therapies for nonautoimmune hyperthyroidism and thyroid cancer. Based on a literature search regarding all published TSHR mutations, this review covers several mutations which are clearly associated with a hyperthyroidism-phenotype, but interestingly show a lack of constitutive activity determined by in vitro characterization. Possible reasons for the observed discrepancies between clinical phenotypes and in vitro characterization results for constitutive TSHR activity are reviewed. All current in vitro characterization methods for constitutive TSHR mutations are "preliminary attempts" and may well be revised by more comprehensive and even better approaches. However, a standardized approach for the determination of constitutive activity can help to identify TSHR mutations for which the investigation of additional signaling mechanisms would be most interesting to find explanations for the current clinical phenotype/in vitro discrepancies and thereby also define suitable methods to explore the physiological relevance of constitutive wild type TSHR activity. © Georg Thieme Verlag KG Stuttgart · New York.

Biology of GDNF and its receptors - Relevance for disorders of the central nervous system.

PubMed

Ibáñez, Carlos F; Andressoo, Jaan-Olle

2017-01-01

A targeted effort to identify novel neurotrophic factors for midbrain dopaminergic neurons resulted in the isolation of GDNF (glial cell line-derived neurotrophic factor) from the supernatant of a rat glial cell line in 1993. Over two decades and 1200 papers later, the GDNF ligand family and their different receptor systems are now recognized as one of the major neurotrophic networks in the nervous system, important for the development, maintenance and function of a variety of neurons and glial cells. The many ways in which the four members of the GDNF ligand family can signal and function allow these factors to take part in the control of multiple types of processes, from neuronal survival to axon guidance and synapse formation in the developing nervous system, to synaptic function and regenerative responses in the adult. In this review, we will briefly summarize basic aspects of GDNF signaling mechanisms and receptor systems and then review our current knowledge of the physiology of GDNF activities in the central nervous system, with an eye to its relevance for neurodegenerative and neuropsychiatric diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Deliberate acquisition of competence in physiological breech birth: A grounded theory study.

PubMed

Walker, Shawn; Scamell, Mandie; Parker, Pam

2018-06-01

Research suggests that the skill and experience of the attendant significantly affect the outcomes of vaginal breech births, yet practitioner experience levels are minimal within many contemporary maternity care systems. Due to minimal experience and cultural resistance, few practitioners offer vaginal breech birth, and many practice guidelines and training programmes recommend delivery techniques requiring supine maternal position. Fewer practitioners have skills to support physiological breech birth, involving active maternal movement and choice of birthing position, including upright postures such as kneeling, standing, squatting, or on a birth stool. How professionals learn complex skills contrary to those taught in their local practice settings is unclear. How do professionals develop competence and expertise in physiological breech birth? Nine midwives and five obstetricians with experience facilitating upright physiological breech births participated in semi-structured interviews. Data were analysed iteratively using constructivist grounded theory methods to develop an empirical theory of physiological breech skill acquisition. Among the participants in this research, the deliberate acquisition of competence in physiological breech birth included stages of affinity with physiological birth, critical awareness, intention, identity and responsibility. Expert practitioners operating across local and national boundaries guided less experienced practitioners. The results depict a specialist learning model which could be formalised in sympathetic training programmes, and evaluated. It may also be relevant to developing competence in other specialist/expert roles and innovative practices. Deliberate development of local communities of practice may support professionals to acquire elusive breech skills in a sustainable way. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

An open-access microfluidic model for lung-specific functional studies at an air-liquid interface.

PubMed

Nalayanda, Divya D; Puleo, Christopher; Fulton, William B; Sharpe, Leilani M; Wang, Tza-Huei; Abdullah, Fizan

2009-10-01

In an effort to improve the physiologic relevance of existing in vitro models for alveolar cells, we present a microfluidic platform which provides an air-interface in a dynamic system combining microfluidic and suspended membrane culture systems. Such a system provides the ability to manipulate multiple parameters on a single platform along with ease in cell seeding and manipulation. The current study presents a comparison of the efficacy of the hybrid system with conventional platforms using assays analyzing the maintenance of function and integrity of A549 alveolar epithelial cell monolayer cultures. The hybrid system incorporates bio-mimetic nourishment on the basal side of the epithelial cells along with an open system on the apical side of the cells exposed to air allowing for easy access for assays.

Emotion recognition based on physiological changes in music listening.

PubMed

Kim, Jonghwa; André, Elisabeth

2008-12-01

Little attention has been paid so far to physiological signals for emotion recognition compared to audiovisual emotion channels such as facial expression or speech. This paper investigates the potential of physiological signals as reliable channels for emotion recognition. All essential stages of an automatic recognition system are discussed, from the recording of a physiological dataset to a feature-based multiclass classification. In order to collect a physiological dataset from multiple subjects over many weeks, we used a musical induction method which spontaneously leads subjects to real emotional states, without any deliberate lab setting. Four-channel biosensors were used to measure electromyogram, electrocardiogram, skin conductivity and respiration changes. A wide range of physiological features from various analysis domains, including time/frequency, entropy, geometric analysis, subband spectra, multiscale entropy, etc., is proposed in order to find the best emotion-relevant features and to correlate them with emotional states. The best features extracted are specified in detail and their effectiveness is proven by classification results. Classification of four musical emotions (positive/high arousal, negative/high arousal, negative/low arousal, positive/low arousal) is performed by using an extended linear discriminant analysis (pLDA). Furthermore, by exploiting a dichotomic property of the 2D emotion model, we develop a novel scheme of emotion-specific multilevel dichotomous classification (EMDC) and compare its performance with direct multiclass classification using the pLDA. Improved recognition accuracy of 95\\% and 70\\% for subject-dependent and subject-independent classification, respectively, is achieved by using the EMDC scheme.

Neuroimmunologic aspects of sleep and sleep loss

NASA Technical Reports Server (NTRS)

Rogers, N. L.; Szuba, M. P.; Staab, J. P.; Evans, D. L.; Dinges, D. F.

2001-01-01

The complex and intimate interactions between the sleep and immune systems have been the focus of study for several years. Immune factors, particularly the interleukins, regulate sleep and in turn are altered by sleep and sleep deprivation. The sleep-wake cycle likewise regulates normal functioning of the immune system. Although a large number of studies have focused on the relationship between the immune system and sleep, relatively few studies have examined the effects of sleep deprivation on immune parameters. Studies of sleep deprivation's effects are important for several reasons. First, in the 21st century, various societal pressures require humans to work longer and sleep less. Sleep deprivation is becoming an occupational hazard in many industries. Second, to garner a greater understanding of the regulatory effects of sleep on the immune system, one must understand the consequences of sleep deprivation on the immune system. Significant detrimental effects on immune functioning can be seen after a few days of total sleep deprivation or even several days of partial sleep deprivation. Interestingly, not all of the changes in immune physiology that occur as a result of sleep deprivation appear to be negative. Numerous medical disorders involving the immune system are associated with changes in the sleep-wake physiology--either being caused by sleep dysfunction or being exacerbated by sleep disruption. These disorders include infectious diseases, fibromyalgia, cancers, and major depressive disorder. In this article, we will describe the relationships between sleep physiology and the immune system, in states of health and disease. Interspersed will be proposals for future research that may illuminate the clinical relevance of the relationships between sleeping, sleep loss and immune function in humans. Copyright 2001 by W.B. Saunders Company.

PACAP receptor pharmacology and agonist bias: analysis in primary neurons and glia from the trigeminal ganglia and transfected cells

PubMed Central

Walker, C S; Sundrum, T; Hay, D L

2014-01-01

Background and Purpose A major challenge in the development of new medicines targeting GPCRs is the ability to quantify drug action in physiologically relevant models. Primary cell models that closely resemble the clinically relevant in vivo site of drug action are important translational tools in drug development. However, pharmacological studies in these models are generally very limited due to the methodology used. Experimental Approach We used a neuropeptide system to demonstrate the applicability of using highly sensitive signalling assays in primary cells. We quantified the action of pituitary adenylate cyclase-activating peptide (PACAP)-38, PACAP-27 and vasoactive intestinal polypeptide in primary cultures of neurons and glia derived from rat trigeminal ganglia (TG), comparing our observations to transfected cells. Key Results PACAP-responsive receptors in rat trigeminal neurons, glia and transfected PAC1n receptors were pharmacologically distinct. PACAP-38, but not PACAP-27, activated ERK in glia, while both forms stimulated cellular cAMP production. PACAP(6–38) also displayed cell-type-dependent, agonist-specific, antagonism. Conclusions and Implications The complexity of PACAP pharmacology in the TG may help to direct, more effectively, the development of disease treatments targeting the PACAP receptor. We suggest that these methodologies are broadly applicable to other primary cell types of human or animal origin, and that our approach may allow more thorough characterization of ligand properties in physiologically relevant cell types. PMID:24303997

Melatonin and male reproductive health: relevance of darkness and antioxidant properties.

PubMed

Rocha, C S; Rato, L; Martins, A D; Alves, M G; Oliveira, P F

2015-01-01

The pineal hormone melatonin controls several physiological functions that reach far beyond the regulation of the circadian rhythm. Moreover, it can be produced in extra-pineal organs such as reproductive organs. The role of melatonin in the mammalian seasonal and circadian rhythm is well known. Nevertheless, its overall effect in male reproductive physiology remains largely unknown. Melatonin is a very powerful endogenous antioxidant that can also be exogenously taken safely. Interestingly, its antioxidant properties have been consistently reported to improve the male reproductive dysfunctions associated with pathological conditions and also with the exposure to toxicants. Nevertheless, the exact molecular mechanisms by which melatonin exerts its action in the male reproductive system remain a matter of debate. Herein, we propose to present an up-to-date overview of the melatonin effects in the male reproductive health and debate future directions to disclose possible sites of melatonin action in male reproductive system. We will discuss not only the role of melatonin during darkness and sleep but also the importance of the antioxidant properties of this hormone to male fertility. Since melatonin readily crosses the physiological barriers, such as the blood-testis barrier, and has a very low toxicity, it appears as an excellent candidate in the prevention and/or treatment of the multiple male reproductive dysfunctions associated with various pathologies.

Humor, laughter, learning, and health! A brief review.

PubMed

Savage, Brandon M; Lujan, Heidi L; Thipparthi, Raghavendar R; DiCarlo, Stephen E

2017-09-01

Human emotions, such as anxiety, depression, fear, joy, and laughter, profoundly affect psychological and physiological processes. These emotions form a set of basic, evolved functions that are shared by all humans. Laughter is part of a universal language of basic emotions that all humans recognize. Health care providers and educators may utilize the power of laughter to improve health and enhance teaching and learning. This is an important consideration because teaching is not just about content: it is also about forming relationships and strengthening human connections. In this context, when used effectively, humor is documented to build relationships and enhance performance. Specifically, humor improves student performance by attracting and sustaining attention, reducing anxiety, enhancing participation, and increasing motivation. Moreover, humor stimulates multiple physiological systems that decrease levels of stress hormones, such as cortisol and epinephrine, and increase the activation of the mesolimbic dopaminergic reward system. To achieve these benefits, it is important to use humor that is relevant to the course content and not disparaging toward others. Self-effacing humor illustrates to students that the teacher is comfortable making mistakes and sharing these experiences with the classroom. In this brief review, we discuss the history and relationship between humor, laughing, learning, and health with an emphasis on the powerful, universal language of laughter. Copyright © 2017 the American Physiological Society.

The Sociophysiology of Caring in the Doctor-patient Relationship

PubMed Central

Adler, Herbert M

2002-01-01

The emotional investment required to construct a caring doctor-patient relationship can be justified on humane grounds. Can it also be justified as a direct physiologic intervention? Two lines of evidence point in this direction. People in an empathic relationship exhibit a correlation of indicators of autonomic activity. This occurs between speakers and responsive listeners, members of a coherent group, and bonded pairs of higher social animals. Furthermore, the experience of feeling cared about in a relationship reduces the secretion of stress hormones and shifts the neuroendocrine system toward homeostasis. Because the social engagement of emotions is simultaneously the social engagement of the physiologic substrate of those emotions, the process has been labeled sociophysiology. This process can influence the health of both parties in the doctor-patient relationship, and may be relevant to third parties.

Lab-on-a-brane: A novel physiologically relevant planar arterial model to study transendothelial transport

NASA Astrophysics Data System (ADS)

Budhwani, Karim Ismail

The tremendous quality of life impact notwithstanding, cardiovascular diseases and Cancer add up to over US$ 700bn each year in financial costs alone. Aging and population growth are expected to further expand the problem space while drug research and development remain expensive. However, preclinical costs can be substantially mitigated by substituting animal models with in vitro devices that accurately model human cardiovascular transport. Here we present a novel physiologically relevant lab-on-a-brane that simulates in vivo pressure, flow, strain, and shear waveforms associated with normal and pathological conditions in large and small blood vessels for studying molecular transport across the endothelial monolayer. The device builds upon previously demonstrated integrated microfluidic loop design by: (a) introducing nanoscale pores in the substrate membrane to enable transmembrane molecular transport, (b) transforming the substrate membrane into a nanofibrous matrix for 3D smooth muscle cell (SMC) tissue culture, (c) integrating electrospinning fabrication methods, (d) engineering an invertible sandwich cell culture device architecture, and (e) devising a healthy co-culture mechanism for human arterial endothelial cell (HAEC) monolayer and multiple layers of human smooth muscle cells (HSMC) to accurately mimic arterial anatomy. Structural and mechanical characterization was conducted using confocal microscopy, SEM, stress/strain analysis, and infrared spectroscopy. Transport was characterized using FITC-Dextran hydraulic permeability protocol. Structure and transport characterization successfully demonstrate device viability as a physiologically relevant arterial mimic for testing transendothelial transport. Thus, our lab-on-a-brane provides a highly effective and efficient, yet considerably inexpensive, physiologically relevant alternative for pharmacokinetic evaluation; possibly reducing animals used in pre-clinical testing, clinical trials cost from false starts, and time-to-market. Furthermore, this platform can be easily configured for testing targeted therapeutic delivery and in multiple simultaneous arrays for personalized and precision medicine applications.

Physiological coherence in healthy volunteers during laboratory-induced stress and controlled breathing.

PubMed

Mejía-Mejía, Elisa; Torres, Robinson; Restrepo, Diana

2018-06-01

Physiological coherence has been related with a general sense of well-being and improvements in health and physical, social, and cognitive performance. The aim of this study was to evaluate the relationship between acute stress, controlled breathing, and physiological coherence, and the degree of body systems synchronization during a coherence-generation exercise. Thirty-four university employees were evaluated during a 20-min test consisting of four stages of 5-min duration each, during which basal measurements were obtained (Stage 1), acute stress was induced using validated mental stressors (Stroop test and mental arithmetic task, during Stage 2 and 3, respectively), and coherence states were generated using a controlled breathing technique (Stage 4). Physiological coherence and cardiorespiratory synchronization were assessed during each stage from heart rate variability, pulse transit time, and respiration. Coherence measurements derived from the three analyzed variables increased during controlled respiration. Moreover, signals synchronized during the controlled breathing stage, implying a cardiorespiratory synchronization was achieved by most participants. Hence, physiological coherence and cardiopulmonary synchronization, which could lead to improvements in health and better life quality, can be achieved using slow, controlled breathing exercises. Meanwhile, coherence measured during basal state and stressful situations did not show relevant differences using heart rate variability and pulse transit time. More studies are needed to evaluate the ability of coherence ratio to reflect acute stress. © 2017 Society for Psychophysiological Research.

Adsorption of doxorubicin on citrate-capped gold nanoparticles: insights into engineering potent chemotherapeutic delivery systems

NASA Astrophysics Data System (ADS)

Curry, Dennis; Cameron, Amanda; MacDonald, Bruce; Nganou, Collins; Scheller, Hope; Marsh, James; Beale, Stefanie; Lu, Mingsheng; Shan, Zhi; Kaliaperumal, Rajendran; Xu, Heping; Servos, Mark; Bennett, Craig; Macquarrie, Stephanie; Oakes, Ken D.; Mkandawire, Martin; Zhang, Xu

2015-11-01

Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates. Electronic supplementary information (ESI) available: DOX-AuNP absorption spectra and colored solution images, citrate displacement data, original DOX-AuNP loading isotherm, XPS data and TEM micrographs, modelling data. See DOI: 10.1039/c5nr05826k

Neural mechanisms of selective attention in the somatosensory system.

PubMed

Gomez-Ramirez, Manuel; Hysaj, Kristjana; Niebur, Ernst

2016-09-01

Selective attention allows organisms to extract behaviorally relevant information while ignoring distracting stimuli that compete for the limited resources of their central nervous systems. Attention is highly flexible, and it can be harnessed to select information based on sensory modality, within-modality feature(s), spatial location, object identity, and/or temporal properties. In this review, we discuss the body of work devoted to understanding mechanisms of selective attention in the somatosensory system. In particular, we describe the effects of attention on tactile behavior and corresponding neural activity in somatosensory cortex. Our focus is on neural mechanisms that select tactile stimuli based on their location on the body (somatotopic-based attention) or their sensory feature (feature-based attention). We highlight parallels between selection mechanisms in touch and other sensory systems and discuss several putative neural coding schemes employed by cortical populations to signal the behavioral relevance of sensory inputs. Specifically, we contrast the advantages and disadvantages of using a gain vs. spike-spike correlation code for representing attended sensory stimuli. We favor a neural network model of tactile attention that is composed of frontal, parietal, and subcortical areas that controls somatosensory cells encoding the relevant stimulus features to enable preferential processing throughout the somatosensory hierarchy. Our review is based on data from noninvasive electrophysiological and imaging data in humans as well as single-unit recordings in nonhuman primates. Copyright © 2016 the American Physiological Society.

PROPOSED MODELS FOR ESTIMATING RELEVANT DOSE RESULTING FROM EXPOSURES BY THE GASTROINTESTINAL ROUTE

EPA Science Inventory

Simple first-order intestinal absorption commonly used in physiologically-based pharmacokinetic(PBPK) models can be made to fit many clinical administrations but may not provide relevant information to extrapolate to real-world exposure scenarios for risk assessment. Small hydr...

Assessment of the Contractile Properties of Permeabilized Skeletal Muscle Fibers.

PubMed

Claflin, Dennis R; Roche, Stuart M; Gumucio, Jonathan P; Mendias, Christopher L; Brooks, Susan V

2016-01-01

Permeabilized individual skeletal muscle fibers offer the opportunity to evaluate contractile behavior in a system that is greatly simplified, yet physiologically relevant. Here we describe the steps required to prepare, permeabilize and preserve small samples of skeletal muscle. We then detail the procedures used to isolate individual fiber segments and attach them to an experimental apparatus for the purpose of controlling activation and measuring force generation. We also describe our technique for estimating the cross-sectional area of fiber segments. The area measurement is necessary for normalizing the absolute force to obtain specific force, a measure of the intrinsic force-generating capability of the contractile system.

The development of multi-model rehabilitation training system for lower limb sitting function

NASA Astrophysics Data System (ADS)

Wu, Jianfeng; Sun, Yue; Wu, Qun

2017-04-01

The multi-model rehabilitation training system was manufactured according to the demands of patients' practical training. Through the use of the patient's exercise physiology information, the ability of muscle force and movement efficiency of the patient were identified. Following with medical rehabilitation therapy, the training model, a combination of active and passive training, was proposed to enhance the training efficiency and rehabilitation effect. Furthermore, taking the sitting movement training as an example, the research theory was applied in knee rehabilitation training. The results of the research provid technical support and practical reference to the relevant training equipment designs and clinical applications.

Vestibular animal models: contributions to understanding physiology and disease.

PubMed

Straka, Hans; Zwergal, Andreas; Cullen, Kathleen E

2016-04-01

Our knowledge of the vestibular sensory system, its functional significance for gaze and posture stabilization, and its capability to ensure accurate spatial orientation perception and spatial navigation has greatly benefitted from experimental approaches using a variety of vertebrate species. This review summarizes the attempts to establish the roles of semicircular canal and otolith endorgans in these functions followed by an overview of the most relevant fields of vestibular research including major findings that have advanced our understanding of how this system exerts its influence on reflexive and cognitive challenges encountered during daily life. In particular, we highlight the contributions of different animal models and the advantage of using a comparative research approach. Cross-species comparisons have established that the morpho-physiological properties underlying vestibular signal processing are evolutionarily inherent, thereby disclosing general principles. Based on the documented success of this approach, we suggest that future research employing a balanced spectrum of standard animal models such as fish/frog, mouse and primate will optimize our progress in understanding vestibular processing in health and disease. Moreover, we propose that this should be further supplemented by research employing more "exotic" species that offer unique experimental access and/or have specific vestibular adaptations due to unusual locomotor capabilities or lifestyles. Taken together this strategy will expedite our understanding of the basic principles underlying vestibular computations to reveal relevant translational aspects. Accordingly, studies employing animal models are indispensible and even mandatory for the development of new treatments, medication and technical aids (implants) for patients with vestibular pathologies.

Anatomy and physiology of the aging neck.

PubMed

Shadfar, Scott; Perkins, Stephen W

2014-05-01

This article discusses the surgically relevant anatomic and physiologic tenets of the aging neck. Procedures performed to rejuvenate and contour the aging neck can be challenging. A thorough understanding of the underlying neck anatomy, as well as the physiology associated with aging, is critical for surgical planning, execution, and achieving aesthetically pleasing outcomes. These topics are reviewed and used as the foundation for a discussion of various other techniques. Copyright © 2014 Elsevier Inc. All rights reserved.

How is physiology relevant to behavior analysis?

PubMed Central

Reese, Hayne W.

1996-01-01

Physiology is an important biological science; but behavior analysis is not a biological science, and behavior analysts can safely ignore biological processes. However, ignoring products of biological processes might be a serious mistake. The important products include behavior, instinctive drift, behavior potentials, hunger, and many developmental milestones and events. Physiology deals with the sources of such products; behavior analysis can deal with how the products affect behavior, which can be understood without understanding their sources. PMID:22478240

Anesthesia in Experimental Stroke Research

PubMed Central

Hoffmann, Ulrike; Sheng, Huaxin; Ayata, Cenk; Warner, David S.

2016-01-01

Anesthetics have enabled major advances in development of experimental models of human stroke. Yet their profound pharmacologic effects on neural function can confound the interpretation of experimental stroke research. Anesthetics have drug and dose-specific effects on cerebral blood flow and metabolism, neurovascular coupling, autoregulation, ischemic depolarizations, excitotoxicity, inflammation, neural networks, and numerous molecular pathways relevant for stroke outcome. Both pre- and post-conditioning properties have been described. Anesthetics also modulate systemic arterial blood pressure, lung ventilation, and thermoregulation, all of which may interact with the ischemic insult as well as the therapeutic interventions. These confounds present a dilemma. Here, we provide an overview of the anesthetic mechanisms of action and molecular and physiologic effects on factors relevant to stroke outcomes that can guide the choice and optimization of the anesthetic regimen in experimental stroke. PMID:27534542

Social aggravation: Understanding the complex role of social relationships on stress and health-relevant physiology.

PubMed

Birmingham, Wendy C; Holt-Lunstad, Julianne

2018-04-05

There is a rich literature on social support and physical health, but research has focused primarily on the protective effects of social relationship. The stress buffering model asserts that relationships may be protective by being a source of support when coping with stress, thereby blunting health relevant physiological responses. Research also indicates relationships can be a source of stress, also influencing health. In other words, the social buffering influence may have a counterpart, a social aggravating influence that has an opposite or opposing effect. Drawing upon existing conceptual models, we expand these to delineate how social relationships may influence stress processes and ultimately health. This review summarizes the existing literature that points to the potential deleterious physiological effects of our relationships when they are sources of stress or exacerbate stress. Copyright © 2018 Elsevier B.V. All rights reserved.

An overview of estrogen-associated endocrine disruption in fishes: evidence of effects on reproductive and immune physiology

USGS Publications Warehouse

Iwanowicz, L.R.; Blazer, V.S.

2011-01-01

Simply and perhaps intuitively defined, endocrine disruption is the abnormal modulation of normal hormonal physiology by exogenous chemicals. In fish, endocrine disruption of the reproductive system has been observed worldwide in numerous species and is known to affect both males and females. Observations of biologically relevant endocrine disruption most commonly occurs near waste water treatment plant outfalls, pulp and paper mills, and areas of high organic loading sometimes associated with agricultural practices. Estrogenic endocrine disrupting chemicals (EEDCs) have received an overwhelmingly disproportionate amount of scientific attention compared to other EDCs in recent years. In male fishes, exposure to EEDCs can lead to the induction of testicular oocytes (intersex), measurable plasma vitellogenin protein, altered sex steroid profiles, abnormal spawning behavior, skewed population sex ratios, and lessened reproductive success. Interestingly, contemporary research purports that EDCs modulate aspects of non-reproductive physiology including immune function. Here we present an overview of endocrine disruption in fishes associated with estrogenic compounds, implications of this phenomenon, and examples of EDC related research findings by our group in the Potomac River Watershed, USA.

Radio telemetry devices to monitor breathing in non-sedated animals.

PubMed

Samson, Nathalie; Dumont, Sylvain; Specq, Marie-Laure; Praud, Jean-Paul

2011-12-15

Radio telemetry equipment has significantly improved over the last 10-15 years and is increasingly being used in research for monitoring a variety of physiological parameters in non-sedated animals. The aim of this review is to provide an update on the current state of development of radio telemetry for recording respiration. Our literature review found only rare reports of respiratory studies via radio telemetry. Much of this article will hence report our experience with our custom-built radio telemetry devices designed for recording respiratory signals, together with numerous other physiological signals in lambs. Our current radio telemetry system allows to record 24 simultaneous signals 24h/day for several days. To our knowledge, this is the highest number of physiological signals, which can be recorded wirelessly. Our devices have been invaluable for studying respiration in our ovine models of preterm birth, reflux laryngitis, postnatal exposure to cigarette smoke, respiratory syncytial virus infection and nasal ventilation, all of which are relevant to neonatal respiratory problems. Copyright © 2011 Elsevier B.V. All rights reserved.

Pupillary Response to Negative Emotional Stimuli Is Differentially Affected in Meditation Practitioners

PubMed Central

Vasquez-Rosati, Alejandra; Brunetti, Enzo P.; Cordero, Carmen; Maldonado, Pedro E.

2017-01-01

Clinically, meditative practices have become increasingly relevant, decreasing anxiety in patients and increasing antibody production. However, few studies have examined the physiological correlates, or effects of the incorporation of meditative practices. Because pupillary reactivity is a marker for autonomic changes and emotional processing, we hypothesized that the pupillary responses of mindfulness meditation practitioners (MP) and subjects without such practices (non-meditators (NM)) differ, reflecting different emotional processing. In a group of 11 MP and 9 NM, we recorded the pupil diameter using video-oculography while subjects explored images with emotional contents. Although both groups showed a similar pupillary response for positive and neutral images, negative images evoked a greater pupillary contraction and a weaker dilation in the MP group. Also, this group had faster physiological recovery to baseline levels. These results suggest that mindfulness meditation practices modulate the response of the autonomic nervous system, reflected in the pupillary response to negative images and faster physiological recovery to baseline levels, suggesting that pupillometry could be used to assess the potential health benefits of these practices in patients. PMID:28515685

MiR-204 down-regulation elicited perturbation of a gene target signature common to human cholangiocarcinoma and gastric cancer.

PubMed

Canu, Valeria; Sacconi, Andrea; Lorenzon, Laura; Biagioni, Francesca; Lo Sardo, Federica; Diodoro, Maria Grazia; Muti, Paola; Garofalo, Alfredo; Strano, Sabrina; D'Errico, Antonietta; Grazi, Gian Luca; Cioce, Mario; Blandino, Giovanni

2017-05-02

There is high need of novel diagnostic and prognostic tools for tumors of the digestive system, such as gastric cancer and cholangiocarcinoma. We recently found that miR-204 was deeply downregulated in gastric cancer tissues. Here we investigated whether this was common to other tumors of the digestive system and whether this elicited a miR-204-dependent gene target signature, diagnostically and therapeutically relevant. Finally, we assessed the contribution of the identified target genes to the cell cycle progression and clonogenicity of gastric cancer and cholangiocarcinoma cell lines. We employed quantitative PCR and Affymetrix profiling for gene expression studies. In silico analysis aided us to identifying a miR-204 target signature in publicly available databases (TGCA). We employed transient transfection experiments, clonogenic assays and cell cycle profiling to evaluate the biological consequences of miR-204 perturbation. We identified a novel miR-204 gene target signature perturbed in gastric cancer and in cholangiocarcinoma specimens. We validated its prognostic relevance and mechanistically addressed its biological relevance in GC and CC cell lines. We suggest that restoring the physiological levels of miR-204 in some gastrointestinal cancers might be exploited therapeutically.

Mechanisms and disease relevance of neutrophil extracellular trap formation.

PubMed

Van Avondt, Kristof; Hartl, Dominik

2018-03-15

While the microscopic appearance of neutrophil extracellular traps (NETs) has fascinated basic researchers since its discovery, the (patho)physiological mechanisms triggering NET release, the disease relevance and clinical translatability of this unconventional cellular mechanism remained poorly understood. Here, we summarize and discuss current concepts of the mechanisms and disease relevance of NET formation. © 2018 Stichting European Society for Clinical Investigation Journal Foundation.

Use of ex vivo and in vitro cultures of the human respiratory tract to study the tropism and host responses of highly pathogenic avian influenza A (H5N1) and other influenza viruses.

PubMed

Chan, Renee W Y; Chan, Michael C W; Nicholls, John M; Malik Peiris, J S

2013-12-05

The tropism of influenza viruses for the human respiratory tract is a key determinant of host-range, and consequently, of pathogenesis and transmission. Insights can be obtained from clinical and autopsy studies of human disease and relevant animal models. Ex vivo cultures of the human respiratory tract and in vitro cultures of primary human cells can provide complementary information provided they are physiologically comparable in relevant characteristics to human tissues in vivo, e.g. virus receptor distribution, state of differentiation. We review different experimental models for their physiological relevance and summarize available data using these cultures in relation to highly pathogenic avian influenza H5N1, in comparison where relevant, with other influenza viruses. Transformed continuous cell-lines often differ in important ways to the corresponding tissues in vivo. The state of differentiation of primary human cells (respiratory epithelium, macrophages) can markedly affect virus tropism and host responses. Ex vivo cultures of human respiratory tissues provide a close resemblance to tissues in vivo and may be used to risk assess animal viruses for pandemic threat. Physiological factors (age, inflammation) can markedly affect virus receptor expression and virus tropism. Taken together with data from clinical studies on infected humans and relevant animal models, data from ex vivo and in vitro cultures of human tissues and cells can provide insights into virus transmission and pathogenesis and may provide understanding that leads to novel therapeutic interventions. Copyright © 2013 Elsevier B.V. All rights reserved.

Enhancing team-sport athlete performance: is altitude training relevant?

PubMed

Billaut, François; Gore, Christopher J; Aughey, Robert J

2012-09-01

Field-based team sport matches are composed of short, high-intensity efforts, interspersed with intervals of rest or submaximal exercise, repeated over a period of 60-120 minutes. Matches may also be played at moderate altitude where the lower oxygen partial pressure exerts a detrimental effect on performance. To enhance run-based performance, team-sport athletes use varied training strategies focusing on different aspects of team-sport physiology, including aerobic, sprint, repeated-sprint and resistance training. Interestingly, 'altitude' training (i.e. living and/or training in O(2)-reduced environments) has only been empirically employed by athletes and coaches to improve the basic characteristics of speed and endurance necessary to excel in team sports. Hypoxia, as an additional stimulus to training, is typically used by endurance athletes to enhance performance at sea level and to prepare for competition at altitude. Several approaches have evolved in the last few decades, which are known to enhance aerobic power and, thus, endurance performance. Altitude training can also promote an increased anaerobic fitness, and may enhance sprint capacity. Therefore, altitude training may confer potentially-beneficial adaptations to team-sport athletes, which have been overlooked in contemporary sport physiology research. Here, we review the current knowledge on the established benefits of altitude training on physiological systems relevant to team-sport performance, and conclude that current evidence supports implementation of altitude training modalities to enhance match physical performances at both sea level and altitude. We hope that this will guide the practice of many athletes and stimulate future research to better refine training programmes.

AGING AND TOXIC RESPONSE: ISSUES RELEVANT TO RISK ASSESSMENT (FINAL)

EPA Science Inventory

EPA has released a final report entitled, Aging and Toxic Response: Issues Relevant to Risk Assessment. This document contributes to the Agency's efforts to better understand the physiology of aging in order to protect the health of older persons, and identifies several d...

Human health and the environment: Predicting plasma protein binding and metabolic clearance rates of environmentally relevant chemicals.

EPA Science Inventory

In silico methods provide a rapid, inexpensive means of screening a wide array of environmentally relevant pollutants, pesticides, fungicides and consumer products for further toxicity testing. Physiologically based pharmacokinetic (PBPK) models bridge the gap between in vitro as...

Mechanical measurement of hydrogen bonded host-guest systems under non-equilibrium, near-physiological conditions.

PubMed

Naranjo, Teresa; Cerrón, Fernando; Nieto-Ortega, Belén; Latorre, Alfonso; Somoza, Álvaro; Ibarra, Borja; Pérez, Emilio M

2017-09-01

Decades after the birth of supramolecular chemistry, there are many techniques to measure noncovalent interactions, such as hydrogen bonding, under equilibrium conditions. As ensembles of molecules rapidly lose coherence, we cannot extrapolate bulk data to single-molecule events under non-equilibrium conditions, more relevant to the dynamics of biological systems. We present a new method that exploits the high force resolution of optical tweezers to measure at the single molecule level the mechanical strength of a hydrogen bonded host-guest pair out of equilibrium and under near-physiological conditions. We utilize a DNA reporter to unambiguously isolate single binding events. The Hamilton receptor-cyanuric acid host-guest system is used as a test bed. The force required to dissociate the host-guest system is ∼17 pN and increases with the pulling rate as expected for a system under non-equilibrium conditions. Blocking one of the hydrogen bonding sites results in a significant decrease of the force-to-break by 1-2 pN, pointing out the ability of the method to resolve subtle changes in the mechanical strength of the binding due to the individual H-bonding components. We believe the method will prove to be a versatile tool to address important questions in supramolecular chemistry.

Heritability of climate-relevant traits in a rainforest skink.

PubMed

Martins, Felipe; Kruuk, Loeske; Llewelyn, John; Moritz, Craig; Phillips, Ben

2018-05-22

There is justified concern about the impact of global warming on the persistence of tropical ectotherms. There is also growing evidence for strong selection on climate-relevant physiological traits. Understanding the evolutionary potential of populations is especially important for low dispersal organisms in isolated populations, because these populations have little choice but to adapt. Despite this, direct estimates of heritability and genetic correlations for physiological traits in ectotherms-which will determine their evolutionary responses to selection-are sparse, especially for reptiles. Here we examine the heritabilities and genetic correlations for a set of four morphological and six climate-relevant physiological traits in an isolated population of an Australian rainforest lizard, Lampropholis coggeri. These traits show considerable variation across populations in this species, suggesting local adaptation. From laboratory crosses, we estimated very low to moderate heritability of temperature-related physiological traits (h 2  < 0.31), but significant and higher heritability of desiccation resistance (h 2 ~0.42). These values contrasted with uniformly higher heritabilities (h 2  > 0.51) for morphological traits. At the phenotypic level, there were positive associations among the morphological traits and between thermal limits. Growth rate was positively correlated with thermal limits, but there was no indication that morphology and physiology were linked in any other way. We found some support for a specialist-generalist trade-off in the thermal performance curve, but otherwise there was no evidence for evolutionary constraints, suggesting broadly labile multivariate trait structure. Our results indicate little potential to respond to selection on thermal traits in this population and provide new insights into the capacity of tropical ectotherms to adapt in situ to rapid climate change.

21st Century Cell Culture for 21st Century Toxicology.

PubMed

Pamies, David; Hartung, Thomas

2017-01-17

There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality. The physiological relevance of such models is further enhanced by the measurement of biomarkers (e.g., key events of pathways), organ specific functionality, and more comprehensive assessment cell responses by high-content methods. These approaches are still rarely combined to create microphysiological systems. The complexity of the combination of these technologies can generate results closer to the in vivo situation but increases the number of parameters to control, bringing some new challenges. In fact, we do not argue that all cell culture needs to be that sophisticated. The efforts taken are determined by the purpose of our experiments and tests. If only a very specific molecular target to cell response is of interest, a very simple model, which reflects this, might be much more suited to allow standardization and high-throughput. However, the less defined the end point of interest and cellular response are, the better we should approximate organ- or tissue-like culture conditions to make physiological responses more probable. Besides these technologic advances, important progress in the quality assurance and reporting on cell cultures as well as the validation of cellular test systems brings the utility of cell cultures to a new level. The advancement and broader implementation of Good Cell Culture Practice (GCCP) is key here. In toxicology, this is a major prerequisite for meaningful and reliable results, ultimately supporting risk assessment and product development decisions.

Effects of manufactured nanomaterials on fishes: a target organ and body systems physiology approach.

PubMed

Handy, R D; Al-Bairuty, G; Al-Jubory, A; Ramsden, C S; Boyle, D; Shaw, B J; Henry, T B

2011-10-01

Manufactured nanomaterials (NM) are already used in consumer products and exposure modelling predicts releases of ng to low µg l(-1) levels of NMs into surface waters. The exposure of aquatic ecosystems, and therefore fishes, to manufactured NMs is inevitable. This review uses a physiological approach to describe the known effects of NMs on the body systems of fishes and to identify the internal target organs, as well as outline aspects of colloid chemistry relevant to fish biology. The acute toxicity data, suggest that the lethal concentration for many NMs is in the mg l(-1) range, and a number of sublethal effects have been reported at concentrations from c. 100 µg to 1 mg l(-1). Exposure to NMs in the water column can cause respiratory toxicity involving altered ventilation, mucus secretion and gill pathology. This may not lead, however, to overt haematological disturbances in the short term. The internal target organs include the liver, spleen and haematopoietic system, kidney, gut and brain; with toxic effects involving oxidative stress, ionoregulatory disturbances and organ pathologies. Some pathology appears to be novel for NMs, such as vascular injury in the brain of rainbow trout Oncorhynchus mykiss with carbon nanotubes. A lack of analytical methods, however, has prevented the reporting of NM concentrations in fish tissues, and the precise uptake mechanisms across the gill or gut are yet to be elucidated. The few dietary exposure studies conducted show no effects on growth or food intake at 10-100 mg kg(-1) inclusions of NMs in the diet of O. mykiss, but there are biochemical disturbances. Early life stages are sensitive to NMs with reports of lethal toxicity and developmental defects. There are many data gaps, however, including how water quality alters physiological responses, effects on immunity and chronic exposure data at environmentally relevant concentrations. Overall, the data so far suggest that the manufactured NMs are not as toxic as some traditional chemicals (e.g. some dissolved metals) and the innovative, responsible, development of nanotechnology should continue, with potential benefits for aquaculture, fisheries and fish health diagnostics. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

The brain as a system of nested but partially overlapping networks. Heuristic relevance of the model for brain physiology and pathology.

PubMed

Agnati, L F; Guidolin, D; Fuxe, K

2007-01-01

A new model of the brain organization is proposed. The model is based on the assumption that a global molecular network enmeshes the entire central nervous system. Thus, brain extra-cellular and intra-cellular molecular networks are proposed to communicate at the level of special plasma membrane regions (e.g., the lipid rafts) where horizontal molecular networks can represent input/output regions allowing the cell to have informational exchanges with the extracellular environment. Furthermore, some "pervasive signals" such as field potentials, pressure waves and thermal gradients that affect large parts of the brain cellular and molecular networks are discussed. Finally, at least two learning paradigms are analyzed taking into account the possible role of Volume Transmission: the so-called model of "temporal difference learning" and the "Turing B-unorganised machine". The relevance of this new view of brain organization for a deeper understanding of some neurophysiological and neuropathological aspects of its function is briefly discussed.

Antenna complexes protect Photosystem I from Photoinhibition

PubMed Central

Alboresi, Alessandro; Ballottari, Matteo; Hienerwadel, Rainer; Giacometti, Giorgio M; Morosinotto, Tomas

2009-01-01

Background Photosystems are composed of two moieties, a reaction center and a peripheral antenna system. In photosynthetic eukaryotes the latter system is composed of proteins belonging to Lhc family. An increasing set of evidences demonstrated how these polypeptides play a relevant physiological function in both light harvesting and photoprotection. Despite the sequence similarity between antenna proteins associated with the two Photosystems, present knowledge on their physiological role is mostly limited to complexes associated to Photosystem II. Results In this work we analyzed the physiological role of Photosystem I antenna system in Arabidopsis thaliana both in vivo and in vitro. Plants depleted in individual antenna polypeptides showed a reduced capacity for photoprotection and an increased production of reactive oxygen species upon high light exposure. In vitro experiments on isolated complexes confirmed that depletion of antenna proteins reduced the resistance of isolated Photosystem I particles to high light and that the antenna is effective in photoprotection only upon the interaction with the core complex. Conclusion We show that antenna proteins play a dual role in Arabidopsis thaliana Photosystem I photoprotection: first, a Photosystem I with an intact antenna system is more resistant to high light because of a reduced production of reactive oxygen species and, second, antenna chlorophyll-proteins are the first target of high light damages. When photoprotection mechanisms become insufficient, the antenna chlorophyll proteins act as fuses: LHCI chlorophylls are degraded while the reaction center photochemical activity is maintained. Differences with respect to photoprotection strategy in Photosystem II, where the reaction center is the first target of photoinhibition, are discussed. PMID:19508723

The (biological) speciation of vanadate(V) as revealed by (51)V NMR: A tribute on Lage Pettersson and his work.

PubMed

Rehder, Dieter

2015-06-01

Four decades of research carried out by Lage Pettersson, his group and his coworkers are reviewed, research that has been directed predominantly towards the speciation of vanadate and systems containing, along with vanadate and co-reactants such as phosphate and peroxide, biologically relevant organics. In particular, those organics have been addressed that either are (potential) ligands for vanadate-derived coordination compounds generated at physiological conditions and/or function as constituents in medicinally interesting oxidovanadium compounds. Examples for molecules introduced in the context of the physiological vanadate-ligand interaction include the dipeptides Pro-Ala, Ala-Gly, Ala-His and Ala-Ser, the serum constituents lactate and citrate, and the nucleobases adenosine and uridine. The speciation in the vanadate-picolinate and vanadate-maltol systems is geared towards insulin-enhancing vanadium drugs. The speciation as a function of pH, ionic strength and the concentration of vanadate and the ligand(s) is based on potentiometric and (51)V NMR investigations, a methodical combination that allows reliable access to composition, formation constants and, to some extent, also structural details for the manifold of species present in aqueous media at physiological pH and beyond. The time frame 1971 to 2014 is reviewed, emphasizing the interval 1985 to 2006, and thus focusing on biologically interesting vanadium systems. Figurative representations from the original literature have been included. Copyright © 2015 Elsevier Inc. All rights reserved.

In Vitro Model Simulating Gastro-Intestinal Digestion in the Pediatric Population (Neonates and Young Infants).

PubMed

Kamstrup, Danna; Berthelsen, Ragna; Sassene, Philip Jonas; Selen, Arzu; Müllertz, Anette

2017-02-01

The focus on drug delivery for the pediatric population has been steadily increasing in the last decades. In terms of developing in vitro models simulating characteristics of the targeted pediatric population, with the purpose of predicting drug product performance after oral administration, it is important to simulate the gastro-intestinal conditions and processes the drug will encounter upon oral administration. When a drug is administered in the fed state, which is commonly the case for neonates, as they are typically fed every 3 h, the digestion of the milk will affect the composition of the fluid available for drug dissolution/solubilization. Therefore, in order to predict the solubilized amount of drug available for absorption, an in vitro model simulating digestion in the gastro-intestinal tract should be utilized. In order to simulate the digestion process and the drug solubilization taking place in vivo, the following aspects should be considered; physiologically relevant media, media volume, use of physiological enzymes in proper amounts, as well as correct pH and addition of relevant co-factors, e.g., bile salts and co-enzymes. Furthermore, physiological transit times and appropriate mixing should be considered and mimicked as close as possible. This paper presents a literature review on physiological factors relevant for digestion and drug solubilization in neonates. Based on the available literature data, a novel in vitro digestion model simulating digestion and drug solubilization in the neonate and young infant pediatric population (2 months old and younger) was designed.

Lab-on-a-brane: nanofibrous polymer membranes to recreate organ-capillary interfaces

NASA Astrophysics Data System (ADS)

Budhwani, Karim I.; Thomas, Vinoy; Sethu, Palaniappan

2016-03-01

Drug discovery is a complex and time consuming process involving significant basic research and preclinical evaluation prior to testing in patients. Preclinical studies rely extensively on animal models which often fail in human trials. Biomimetic microphysiological systems (MPS) using human cells can be a promising alternative to animal models; where critical interactions between different organ systems are recreated to provide physiologically relevant in vitro human models. Central here are blood-vessel networks, the interface controlling transport of cellular and biomolecular components between the circulating fluid and underlying tissue. Here we present a novel lab-on-a-brane (or lab-on-a-membrane) nanofluidics MPS that combines the elegance of lab-on-a-chip with the more realistic morphology of 3D fibrous tissue-engineering constructs. Our blood-vessel lab-on-a-brane effectively simulates in vivo vessel-tissue interface for evaluating transendothelial transport in various pharmacokinetic and nanomedicine applications. Attributes of our platform include (a) nanoporous barrier interface enabling transmembrane molecular transport, (b) transformation of substrate into nanofibrous 3D tissue matrix, (c) invertible-sandwich architecture, and (d) simple co-culture mechanism for endothelial and smooth muscle layers to accurately mimic arterial anatomy. Structural, mechanical, and transport characterization using scanning electron microscopy, stress/strain analysis, infrared spectroscopy, immunofluorescence, and FITC-Dextran hydraulic permeability confirm viability of this in vitro system. Thus, our lab-on-a-brane provides an effective and efficient, yet considerably inexpensive, physiologically relevant alternative for pharmacokinetic evaluation; possibly reducing animals used in preclinical testing, costs from false starts, and time-to-market. Furthermore, it can be configured in multiple simultaneous arrays for personalized and precision medicine applications and for evaluating localized and targeted therapeutic delivery.

Malondialdehyde epitopes as targets of immunity and the implications for atherosclerosis

PubMed Central

Binder, Christoph J.

2018-01-01

Accumulating evidence suggests that oxidation-specific epitopes (OSEs) constitute a novel class of damage-associated molecular patterns (DAMPs) generated during high oxidative stress but also in the physiological process of apoptosis. To deal with the potentially harmful consequences of such epitopes, the immune system has developed several mechanisms to protect from OSEs and to orchestrate their clearance, including IgM natural antibodies and both cellular and membrane-bound receptors. Here, we focus on malondialdehyde (MDA) epitopes as prominent examples of OSEs that trigger both innate and adaptive immune responses. First, we review the mechanism of MDA generation, the different types of adducts on various biomolecules and provide relevant examples for physiological carriers of MDA such as apoptotic cells, microvesicles (MV) or oxidized low-density lipoproteins (LDL). Based on recent insights, we argue that MDA epitopes contribute to the maintenance of homeostatic functions by acting as markers of elevated oxidative stress and tissue damage. We discuss multiple lines of evidence that MDA epitopes are pro-inflammatory and thus important targets of innate and adaptive immune responses. Finally, we illustrate the relevance of MDA epitopes in human pathologies by describing their capacity to drive inflammatory processes in atherosclerosis and highlighting protective mechanisms of immunity that could be exploited for therapeutic purposes. PMID:27235680

An inside look at the sensory biology of triatomines.

PubMed

Barrozo, Romina B; Reisenman, Carolina E; Guerenstein, Pablo; Lazzari, Claudio R; Lorenzo, Marcelo G

Although kissing bugs (Triatominae: Reduviidae) are perhaps best known as vectors of Chagas disease, they are important experimental models in studies of insect sensory physiology, pioneered by the seminal studies of Wigglesworth and Gillet more than eighty years ago. Since then, many investigations have revealed that the thermal, hygric, visual and olfactory senses play critical roles in the orientation of these blood-sucking insects towards hosts. Here we review the current knowledge about the role of these sensory systems, focussing on relevant stimuli, sensory structures, receptor physiology and the molecular players involved in the complex and cryptic behavioural repertoire of these nocturnal insects. Odours are particularly relevant, as they are involved in host search and are used for sexual, aggregation and alarm communication. Tastants are critical for a proper recognition of hosts, food and conspecifics. Heat and relative humidity mediate orientation towards hosts and are also important for the selection of resting places. Vision, which mediates negative phototaxis and flight dispersion, is also critical for modulating shelter use and mediating escape responses. The molecular bases underlying the detection of sensory stimuli started to be uncovered by means of functional genetics due to both the recent publication of the genome sequence of Rhodnius prolixus and the availability of modern genome editing techniques. Copyright © 2016 Elsevier Ltd. All rights reserved.

From Claude Bernard to the Batcave and Beyond: Using Batman as a Hook for Physiology Education

ERIC Educational Resources Information Center

Zehr, E. Paul

2011-01-01

Communicating physiology to the general public and popularizing science can be tremendously rewarding activities. Providing relevant and compelling points of linkage, however, between the scientific experiences and the interests of the general public can be challenging. One avenue for popularizing science is to link scientific concepts to images,…

The Emergent Coordination of Cognitive Function

ERIC Educational Resources Information Center

Kello, Christopher T.; Beltz, Brandon C.; Holden, John G.; Van Orden, Guy C.

2007-01-01

1/f scaling has been observed throughout human physiology and behavior, but its origins and meaning remain a matter of debate. Some argue that it is a byproduct of ongoing processes in the brain or body and therefore of limited relevance to psychological theory. Others argue that 1/f scaling reflects a fundamental aspect of all physiological and…

Challenges of physiological monitoring in a Navy operational setting

NASA Technical Reports Server (NTRS)

Banta, Guy R.

1988-01-01

Challenges to physiological monitoring in the Navy include environmental extremes, acceptance of use by test subjects, data transfer, data interpretation, and capability of relating collected data to valid operational relevant criterion measures. These problems are discussed with respect to diving, electrophysiological monitoring, in-flight monitoring, aircrew fatigue, in-flight cardiac stress, and in-flight monitoring devices.

Assessment of autonomic response by broad-band respiration

NASA Technical Reports Server (NTRS)

Berger, R. D.; Saul, J. P.; Cohen, R. J.

1989-01-01

We present a technique for introducing broad-band respiratory perturbations so that the response characteristics of the autonomic nervous system can be determined noninvasively over a wide range of physiologically relevant frequencies. A subject's respiratory bandwidth was broadened by breathing on cue to a sequence of audible tones spaced by Poisson intervals. The transfer function between the respiratory input and the resulting instantaneous heart rate was then computed using spectral analysis techniques. Results using this method are comparable to those found using traditional techniques, but are obtained with an economy of data collection.

Trends in sensorimotor research and countermeasures for exploration-class space flights.

PubMed

Shelhamer, Mark

2015-01-01

Research in the area of sensorimotor and neurovestibular function has played an important role in enabling human space flight. This role, however, is changing. One of the key aspects of sensorimotor function relevant to this role will build on its widespread connections with other physiological and psychological systems in the body. The firm knowledge base in this area can provide a strong platform to explore these interactions, which can also provide for the development of effective and efficient countermeasures to the deleterious effects of space flight.

Oxygen Tension Modulates Differentiation and Primary Macrophage Functions in the Human Monocytic THP-1 Cell Line

PubMed Central

Grodzki, Ana Cristina G.; Giulivi, Cecilia; Lein, Pamela J.

2013-01-01

The human THP-1 cell line is widely used as an in vitro model system for studying macrophage differentiation and function. Conventional culture conditions for these cells consist of ambient oxygen pressure (∼20% v/v) and medium supplemented with the thiol 2-mercaptoethanol (2-ME) and serum. In consideration of the redox activities of O2 and 2-ME, and the extensive experimental evidence supporting a role for reactive oxygen species (ROS) in the differentiation and function of macrophages, we addressed the question of whether culturing THP-1 cells under a more physiologically relevant oxygen tension (5% O2) in the absence of 2-ME and serum would alter THP-1 cell physiology. Comparisons of cultures maintained in 18% O2 versus 5% O2 indicated that reducing oxygen tension had no effect on the proliferation of undifferentiated THP-1 cells. However, decreasing the oxygen tension to 5% O2 significantly increased the rate of phorbol ester-induced differentiation of THP-1 cells into macrophage-like cells as well as the metabolic activity of both undifferentiated and PMA-differentiated THP-1 cells. Removal of both 2-ME and serum from the medium decreased the proliferation of undifferentiated THP-1 cells but increased metabolic activity and the rate of differentiation under either oxygen tension. In differentiated THP-1 cells, lowering the oxygen tension to 5% O2 decreased phagocytic activity, the constitutive release of β-hexosaminidase and LPS-induced NF-κB activation but enhanced LPS-stimulated release of cytokines. Collectively, these data demonstrate that oxygen tension influences THP-1 cell differentiation and primary macrophage functions, and suggest that culturing these cells under tightly regulated oxygen tension in the absence of exogenous reducing agent and serum is likely to provide a physiologically relevant baseline from which to study the role of the local redox environment in regulating THP-1 cell physiology. PMID:23355903

Hormonal regulation of longevity in mammals

PubMed Central

Brown-Borg, Holly M.

2007-01-01

Multiple biological and environmental factors impact the life span of an organism. The endocrine system is a highly integrated physiological system in mammals that regulates metabolism, growth, reproduction, and response to stress, among other functions. As such, this pervasive entity has a major influence on aging and longevity. The growth hormone, insulin-like growth factor-1 and insulin pathways have been at the forefront of hormonal control of aging research in the last few years. Other hormones, including those from the thyroid and reproductive system have also been studied in terms of life span regulation. The relevance of these hormones to human longevity remains to be established, however the evidence from other species including yeast, nematodes, and flies suggest that evolutionarily well-conserved mechanisms are at play and the endocrine system is a key determinant. PMID:17360245

Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

PubMed

Park, Gun-Seok; Park, Min Hee; Shin, Woojung; Zhao, Connie; Sheikh, Sameer; Oh, So Jung; Kim, Hyun Jung

2017-06-01

The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.

The G protein-coupled receptor GPR34 - The past 20 years of a grownup.

PubMed

Schöneberg, Torsten; Meister, Jaroslawna; Knierim, Alexander Bernd; Schulz, Angela

2018-04-22

Research on GPR34, which was discovered in 1999 as an orphan G protein-coupled receptor of the rhodopsin-like class, disclosed its physiologic relevance only piece by piece. Being present in all recent vertebrate genomes analyzed so far it seems to improve the fitness of species although it is not essential for life and reproduction as GPR34-deficient mice demonstrate. However, closer inspection of macrophages and microglia, where it is mainly expressed, revealed its relevance in immune cell function. Recent data clearly demonstrate that GPR34 function is required to arrest microglia in the M0 homeostatic non-phagocytic phenotype. Herein, we summarize the current knowledge on its evolution, genomic and structural organization, physiology, pharmacology and relevance in human diseases including neurodegenerative diseases and cancer, which accumulated over the last 20 years. Copyright © 2018 Elsevier Inc. All rights reserved.

Assessing the Effectiveness of Neurofeedback Training in the Context of Clinical and Social Neuroscience

PubMed Central

Orndorff-Plunkett, Franklin; Singh, Fiza

2017-01-01

Social neuroscience benefits from the experimental manipulation of neuronal activity. One possible manipulation, neurofeedback, is an operant conditioning-based technique in which individuals sense, interact with, and manage their own physiological and mental states. Neurofeedback has been applied to a wide variety of psychiatric illnesses, as well as to treat sub-clinical symptoms, and even to enhance performance in healthy populations. Despite growing interest, there persists a level of distrust and/or bias in the medical and research communities in the USA toward neurofeedback and other functional interventions. As a result, neurofeedback has been largely ignored, or disregarded within social neuroscience. We propose a systematic, empirically-based approach for assessing the effectiveness, and utility of neurofeedback. To that end, we use the term perturbative physiologic plasticity to suggest that biological systems function as an integrated whole that can be perturbed and guided, either directly or indirectly, into different physiological states. When the intention is to normalize the system, e.g., via neurofeedback, we describe it as self-directed neuroplasticity, whose outcome is persistent functional, structural, and behavioral changes. We argue that changes in physiological, neuropsychological, behavioral, interpersonal, and societal functioning following neurofeedback can serve as objective indices and as the metrics necessary for assessing levels of efficacy. In this chapter, we examine the effects of neurofeedback on functional connectivity in a few clinical disorders as case studies for this approach. We believe this broader perspective will open new avenues of investigation, especially within social neuroscience, to further elucidate the mechanisms and effectiveness of these types of interventions, and their relevance to basic research. PMID:28783134

Assessing the Effectiveness of Neurofeedback Training in the Context of Clinical and Social Neuroscience.

PubMed

Orndorff-Plunkett, Franklin; Singh, Fiza; Aragón, Oriana R; Pineda, Jaime A

2017-08-07

Social neuroscience benefits from the experimental manipulation of neuronal activity. One possible manipulation, neurofeedback, is an operant conditioning-based technique in which individuals sense, interact with, and manage their own physiological and mental states. Neurofeedback has been applied to a wide variety of psychiatric illnesses, as well as to treat sub-clinical symptoms, and even to enhance performance in healthy populations. Despite growing interest, there persists a level of distrust and/or bias in the medical and research communities in the USA toward neurofeedback and other functional interventions. As a result, neurofeedback has been largely ignored, or disregarded within social neuroscience. We propose a systematic, empirically-based approach for assessing the effectiveness, and utility of neurofeedback. To that end, we use the term perturbative physiologic plasticity to suggest that biological systems function as an integrated whole that can be perturbed and guided, either directly or indirectly, into different physiological states. When the intention is to normalize the system, e.g., via neurofeedback, we describe it as self-directed neuroplasticity, whose outcome is persistent functional, structural, and behavioral changes. We argue that changes in physiological, neuropsychological, behavioral, interpersonal, and societal functioning following neurofeedback can serve as objective indices and as the metrics necessary for assessing levels of efficacy. In this chapter, we examine the effects of neurofeedback on functional connectivity in a few clinical disorders as case studies for this approach. We believe this broader perspective will open new avenues of investigation, especially within social neuroscience, to further elucidate the mechanisms and effectiveness of these types of interventions, and their relevance to basic research.

Dynamic systems approaches and levels of analysis in the nervous system

PubMed Central

Parker, David; Srivastava, Vipin

2013-01-01

Various analyses are applied to physiological signals. While epistemological diversity is necessary to address effects at different levels, there is often a sense of competition between analyses rather than integration. This is evidenced by the differences in the criteria needed to claim understanding in different approaches. In the nervous system, neuronal analyses that attempt to explain network outputs in cellular and synaptic terms are rightly criticized as being insufficient to explain global effects, emergent or otherwise, while higher-level statistical and mathematical analyses can provide quantitative descriptions of outputs but can only hypothesize on their underlying mechanisms. The major gap in neuroscience is arguably our inability to translate what should be seen as complementary effects between levels. We thus ultimately need approaches that allow us to bridge between different spatial and temporal levels. Analytical approaches derived from critical phenomena in the physical sciences are increasingly being applied to physiological systems, including the nervous system, and claim to provide novel insight into physiological mechanisms and opportunities for their control. Analyses of criticality have suggested several important insights that should be considered in cellular analyses. However, there is a mismatch between lower-level neurophysiological approaches and statistical phenomenological analyses that assume that lower-level effects can be abstracted away, which means that these effects are unknown or inaccessible to experimentalists. As a result experimental designs often generate data that is insufficient for analyses of criticality. This review considers the relevance of insights from analyses of criticality to neuronal network analyses, and highlights that to move the analyses forward and close the gap between the theoretical and neurobiological levels, it is necessary to consider that effects at each level are complementary rather than in competition. PMID:23386835

Monitoring thioredoxin redox with a genetically encoded red fluorescent biosensor.

PubMed

Fan, Yichong; Makar, Merna; Wang, Michael X; Ai, Hui-Wang

2017-09-01

Thioredoxin (Trx) is one of the two major thiol antioxidants, playing essential roles in redox homeostasis and signaling. Despite its importance, there is a lack of methods for monitoring Trx redox dynamics in live cells, hindering a better understanding of physiological and pathological roles of the Trx redox system. In this work, we developed the first genetically encoded fluorescent biosensor for Trx redox by engineering a redox relay between the active-site cysteines of human Trx1 and rxRFP1, a redox-sensitive red fluorescent protein. We used the resultant biosensor-TrxRFP1-to selectively monitor perturbations of Trx redox in various mammalian cell lines. We subcellularly localized TrxRFP1 to image compartmentalized Trx redox changes. We further combined TrxRFP1 with a green fluorescent Grx1-roGFP2 biosensor to simultaneously monitor Trx and glutathione redox dynamics in live cells in response to chemical and physiologically relevant stimuli.

Interspecies chemical communication in bacterial development.

PubMed

Straight, Paul D; Kolter, Roberto

2009-01-01

Our view of bacteria, from the earliest observations through the heyday of antibiotic discovery, has shifted dramatically. We recognize communities of bacteria as integral and functionally important components of diverse habitats, ranging from soil collectives to the human microbiome. To function as productive communities, bacteria coordinate metabolic functions, often requiring shifts in growth and development. The hallmark of cellular development, which we characterize as physiological change in response to environmental stimuli, is a defining feature of many bacterial interspecies interactions. Bacterial communities rely on chemical exchanges to provide the cues for developmental change. Traditional methods in microbiology focus on isolation and characterization of bacteria in monoculture, separating the organisms from the surroundings in which interspecies chemical communication has relevance. Developing multispecies experimental systems that incorporate knowledge of bacterial physiology and metabolism with insights from biodiversity and metagenomics shows great promise for understanding interspecies chemical communication in the microbial world.

Comparison of reduced models for blood flow using Runge–Kutta discontinuous Galerkin methods

PubMed Central

Puelz, Charles; Čanić, Sunčica; Rivière, Béatrice; Rusin, Craig G.

2017-01-01

One–dimensional blood flow models take the general form of nonlinear hyperbolic systems but differ in their formulation. One class of models considers the physically conserved quantities of mass and momentum, while another class describes mass and velocity. Further, the averaging process employed in the model derivation requires the specification of the axial velocity profile; this choice differentiates models within each class. Discrepancies among differing models have yet to be investigated. In this paper, we comment on some theoretical differences among models and systematically compare them for physiologically relevant vessel parameters, network topology, and boundary data. In particular, the effect of the velocity profile is investigated in the cases of both smooth and discontinuous solutions, and a recommendation for a physiological model is provided. The models are discretized by a class of Runge–Kutta discontinuous Galerkin methods. PMID:29081563

Analyzing the texture changes in the quantitative phase maps of adipocytes

NASA Astrophysics Data System (ADS)

Roitshtain, Darina; Sharabani-Yosef, Orna; Gefen, Amit; Shaked, Natan T.

2016-03-01

We present a new analysis tool for studying texture changes in the quantitative phase maps of live cells acquired by wide-field interferometry. The sensitivity of wide-field interferometry systems to small changes in refractive index enables visualizing cells and inner cell organelles without the using fluorescent dyes or other cell-invasive approaches, which may affect the measurement and require external labeling. Our label-free texture-analysis tool is based directly on the optical path delay profile of the sample and does not necessitate decoupling refractive index and thickness in the cell quantitative phase profile; thus, relevant parameters can be calculated using a single-frame acquisition. Our experimental system includes low-coherence wide-field interferometer, combined with simultaneous florescence microscopy system for validation. We used this system and analysis tool for studying lipid droplets formation in adipocytes. The latter demonstration is relevant for various cellular functions such as lipid metabolism, protein storage and degradation to viral replication. These processes are functionally linked to several physiological and pathological conditions, including obesity and metabolic diseases. Quantification of these biological phenomena based on the texture changes in the cell phase map has a potential as a new cellular diagnosis tool.

Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.

PubMed

Budak, Erdal; Fernández Sánchez, Manuel; Bellver, José; Cerveró, Ana; Simón, Carlos; Pellicer, Antonio

2006-06-01

To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic-pituitary-gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. A MEDLINE computer search was performed to identify relevant articles. Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these hormones may act on the central nervous system to initiate the complex process of puberty and maintain normal reproductive function. In addition, leptin and ghrelin and their receptors are involved in reproductive events such as gonadal function, embryo development, and embryo-endometrial interaction. Leptin and ghrelin and other adipose tissue-secreted hormones have significant effects on reproduction. Acting through the brain, these hormones may serve as links between adipose tissue and the reproductive system to supply and regulate energy needs for normal reproduction and pregnancy. Future studies are needed to further clarify the role of these hormones in reproductive events and other related gynecological conditions.

Cellular and Physiological Effects of Anthrax Exotoxin and Its Relevance to Disease

PubMed Central

Lowe, David E.; Glomski, Ian J.

2012-01-01

Bacillus anthracis, the causative agent of anthrax, secretes a tri-partite exotoxin that exerts pleiotropic effects on the host. The purification of the exotoxin components, protective antigen, lethal factor, and edema factor allowed the rapid characterization of their physiologic effects on the host. As molecular biology matured, interest focused on the molecular mechanisms and cellular alterations induced by intoxication. Only recently have researchers begun to connect molecular and cellular knowledge back to the broader physiological effects of the exotoxin. This review focuses on the progress that has been made bridging molecular knowledge back to the exotoxin’s physiological effects on the host. PMID:22919667

Clinically Relevant Levels of 4-Aminopyridine Strengthen Physiological Responses in Intact Motor Circuits in Rats, Especially After Pyramidal Tract Injury.

PubMed

Sindhurakar, Anil; Mishra, Asht M; Gupta, Disha; Iaci, Jennifer F; Parry, Tom J; Carmel, Jason B

2017-04-01

4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.

Capillary response to skeletal muscle contraction: evidence that redundancy between vasodilators is physiologically relevant during active hyperaemia.

PubMed

Lamb, Iain R; Novielli, Nicole M; Murrant, Coral L

2018-04-15

The current theory behind matching blood flow to metabolic demand of skeletal muscle suggests redundant interactions between metabolic vasodilators. Capillaries play an important role in blood flow control given their ability to respond to muscle contraction by causing conducted vasodilatation in upstream arterioles that control their perfusion. We sought to determine whether redundancies occur between vasodilators at the level of the capillary by stimulating the capillaries with muscle contraction and vasodilators relevant to muscle contraction. We identified redundancies between potassium and both adenosine and nitric oxide, between nitric oxide and potassium, and between adenosine and both potassium and nitric oxide. During muscle contraction, we demonstrate redundancies between potassium and nitric oxide as well as between potassium and adenosine. Our data show that redundancy is physiologically relevant and involved in the coordination of the vasodilator response during muscle contraction at the level of the capillaries. We sought to determine if redundancy between vasodilators is physiologically relevant during active hyperaemia. As inhibitory interactions between vasodilators are indicative of redundancy, we tested whether vasodilators implicated in mediating active hyperaemia (potassium (K + ), adenosine (ADO) and nitric oxide (NO)) inhibit one another's vasodilatory effects through direct application of pharmacological agents and during muscle contraction. Using the hamster cremaster muscle and intravital microscopy, we locally stimulated capillaries with one vasodilator in the absence and the presence of a second vasodilator (10 -7 m S-nitroso-N-acetylpenicillamine (SNAP), 10 -7 m ADO, 10 mm KCl) applied sequentially and simultaneously, and observed the response in the associated upstream 4A arteriole controlling the perfusion of the stimulated capillary. We found that KCl significantly attenuated SNAP- and ADO-induced vasodilatations by ∼49.7% and ∼128.0% respectively and ADO significantly attenuated KCl- and SNAP-induced vasodilatations by ∼94.7% and ∼59.6%, respectively. NO significantly attenuated KCl vasodilatation by 93.8%. Further, during muscle contraction we found that inhibition of NO production using l-N G -nitroarginine methyl ester and inhibition of ADO receptors using xanthine amine congener was effective at inhibiting contraction-induced vasodilatation but only in the presence of K + release channel inhibition. Thus, only when the inhibiting vasodilator K + was blocked was the second vasodilator, NO or ADO, able to produce effective vasodilatation. Therefore, we show that there are inhibitory interactions between specific vasodilators at the level of the capillary. Further, these inhibitions can be observed during muscle contraction indicating that redundancies between vasodilators are physiologically relevant and influence vasodilatation during active hyperaemia. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Trauma scoring systems and databases.

PubMed

Lecky, F; Woodford, M; Edwards, A; Bouamra, O; Coats, T

2014-08-01

This review considers current trauma scoring systems and databases and their relevance to improving patient care. Single physiological measures such as systolic arterial pressure have limited ability to diagnose severe trauma by reflecting raised intracranial pressure, or significant haemorrhage. The Glasgow coma score has the greatest prognostic value in head-injured and other trauma patients. Trauma triage tools and imaging decision rules-using combinations of physiological cut-off measures with mechanism of injury and other categorical variables-bring both increased sophistication and increased complexity. It is important for clinicians and managers to be aware of the diagnostic properties (over- and under-triage rates) of any triage tool or decision rule used in their trauma system. Trauma registries are able to collate definitive injury descriptors and use survival prediction models to guide trauma system governance, through individual patient review and case-mix-adjusted benchmarking of hospital and network performance with robust outlier identification. Interrupted time series allow observation in the changes in care processes and outcomes at national level, which can feed back into clinical quality-based commissioning of healthcare. Registry data are also a valuable resource for trauma epidemiological and comparative effectiveness research studies. © The Author 2014. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Salubrious effects of oxytocin on social stress-induced deficits

PubMed Central

Smith, Adam S.; Wang, Zuoxin

2012-01-01

Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

[Modality specific systems of representation and processing of information. Superfluous images, useful representations, necessary evil or inevitable consequences of optimal stimulus processing].

PubMed

Zimmer, H D

1993-01-01

It is discussed what is underlying the assumption of modality-specific processing systems and representations. Starting from the information processing approach relevant aspects of mental representations and their physiological realizations are discussed. Then three different forms of modality-specific systems are distinguished: as stimulus specific processing, as specific informational formats, and as modular part systems. Parallel to that three kinds of analogue systems are differentiated: as holding an analogue-relation, as having a specific informational format and as a set of specific processing constraints. These different aspects of the assumption of modality-specific systems are demonstrated in the example of visual and spatial information processing. It is concluded that postulating information-specific systems is not a superfluous assumption, but it is necessary, and even more likely it is an inevitable consequence of an optimization of stimulus processing.

Clinical metabolomics paves the way towards future healthcare strategies

PubMed Central

Collino, Sebastiano; Martin, François‐Pierre J.; Rezzi, Serge

2013-01-01

Metabolomics is recognized as a powerful top‐down system biological approach to understand genetic‐environment‐health paradigms paving new avenues to identify clinically relevant biomarkers. It is nowadays commonly used in clinical applications shedding new light on physiological regulatory processes of complex mammalian systems with regard to disease aetiology, diagnostic stratification and, potentially, mechanism of action of therapeutic solutions. A key feature of metabolomics lies in its ability to underpin the complex metabolic interactions of the host with its commensal microbial partners providing a new way to define individual and population phenotypes. This review aims at describing recent applications of metabolomics in clinical fields with insight into diseases, diagnostics/monitoring and improvement of homeostatic metabolic regulation. PMID:22348240

Melatonin: Buffering the Immune System

PubMed Central

Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

2013-01-01

Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

Review: welfare of dairy cows in continuously housed and pasture-based production systems.

PubMed

Arnott, G; Ferris, C P; O'Connell, N E

2017-02-01

There is increasing interest in the use of continuous housing systems for dairy cows, with various reasons put forward to advocate such systems. However, the welfare of dairy cows is typically perceived to be better within pasture-based systems, although such judgements are often not scientifically based. The aim of this review was to interrogate the existing scientific literature to compare the welfare, including health, of dairy cows in continuously housed and pasture-based systems. Although summarising existing work, knowledge gaps and directions for future research are also identified. The scope of the review is broad, examining relevant topics under three main headings; health, behaviour and physiology. Regarding health, cows on pasture-based systems had lower levels of lameness, hoof pathologies, hock lesions, mastitis, uterine disease and mortality compared with cows on continuously housed systems. Pasture access also had benefits for dairy cow behaviour, in terms of grazing, improved lying/resting times and lower levels of aggression. Moreover, when given the choice between pasture and indoor housing, cows showed an overall preference for pasture, particularly at night. However, the review highlighted the need for a deeper understanding of cow preference and behaviour. Potential areas for concern within pasture-based systems included physiological indicators of more severe negative energy balance, and in some situations, the potential for compromised welfare with exposure to unpredictable weather conditions. In summary, the results from this review highlight that there remain considerable animal welfare benefits from incorporating pasture access into dairy production systems.

Neuropeptide Y (NPY) and posttraumatic stress disorder (PTSD): A translational update.

PubMed

Schmeltzer, Sarah N; Herman, James P; Sah, Renu

2016-10-01

Posttraumatic stress disorder (PTSD) is a trauma-evoked syndrome, with variable prevalence within the human population due to individual differences in coping and resiliency. In this review, we discuss evidence supporting the relevance of neuropeptide Y (NPY), a stress regulatory transmitter in PTSD. We consolidate findings from preclinical, clinical, and translational studies of NPY that are of relevance to PTSD with an attempt to provide a current update of this area of research. NPY is abundantly expressed in forebrain limbic and brainstem areas that regulate stress and emotional behaviors. Studies in rodents demonstrate a role for NPY in stress responses, anxiety, fear, and autonomic regulation, all relevant to PTSD symptomology. Genetic studies support an association of NPY polymorphisms with stress coping and affect. Importantly, cerebrospinal fluid (CSF) measurements in combat veterans provide direct evidence of NPY association with PTSD diagnosis and symptomology. In addition, NPY involvement in pain, depression, addiction, and metabolism may be relevant to comorbidities associated with PTSD. Collectively, the literature supports the relevance of NPY to PTSD pathophysiology, although knowledge gaps remain. The NPY system is an attractive target in terms of understanding the physiological basis of PTSD as well as treatment of the disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Functional Comparison of Neuronal Cells Differentiated from Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Different Oxygen and Medium Conditions.

PubMed

Yamazaki, Kazuto; Fukushima, Kazuyuki; Sugawara, Michiko; Tabata, Yoshikuni; Imaizumi, Yoichi; Ishihara, Yasuharu; Ito, Masashi; Tsukahara, Kappei; Kohyama, Jun; Okano, Hideyuki

2016-12-01

Because neurons are difficult to obtain from humans, generating functional neurons from human induced pluripotent stem cells (hiPSCs) is important for establishing physiological or disease-relevant screening systems for drug discovery. To examine the culture conditions leading to efficient differentiation of functional neural cells, we investigated the effects of oxygen stress (2% or 20% O 2 ) and differentiation medium (DMEM/F12:Neurobasal-based [DN] or commercial [PhoenixSongs Biologicals; PS]) on the expression of genes related to neural differentiation, glutamate receptor function, and the formation of networks of neurons differentiated from hiPSCs (201B7) via long-term self-renewing neuroepithelial-like stem (lt-NES) cells. Expression of genes related to neural differentiation occurred more quickly in PS and/or 2% O 2 than in DN and/or 20% O 2 , resulting in high responsiveness of neural cells to glutamate, N-methyl-d-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), and ( S)-3,5-dihydroxyphenylglycine (an agonist for mGluR 1/5 ), as revealed by calcium imaging assays. NMDA receptors, AMPA receptors, mGluR 1 , and mGluR 5 were functionally validated by using the specific antagonists MK-801, NBQX, JNJ16259685, and 2-methyl-6-(phenylethynyl)-pyridine, respectively. Multielectrode array analysis showed that spontaneous firing occurred earlier in cells cultured in 2% O 2 than in 20% O 2 . Optimization of O 2 tension and culture medium for neural differentiation of hiPSCs can efficiently generate physiologically relevant cells for screening systems.

Peripheral chemoreceptors and cardiorespiratory coupling: a link to sympatho-excitation.

PubMed

Zoccal, Daniel B

2015-02-01

What is the topic of this review? Chronic intermittent hypoxia (CIH), as observed in patients with obstructive sleep apnoea, is associated with the development of sympathetically mediated arterial hypertension. Nevertheless, the mechanisms underpinning the augmented sympathetic outflow in CIH still remain under investigation. What advances does it highlight? In this report, I present experimental evidence supporting the hypothesis that changes in the function of the respiratory network and coupling with the sympathetic nervous system may be considered as a novel and relevant mechanism for the increase in baseline sympathetic outflow in animals submitted to CIH. Chronic intermittent hypoxia (CIH) has been identified as a relevant risk factor for the development of enhanced sympathetic outflow and arterial hypertension. Several studies have highlighted the importance of peripheral chemoreceptors for the cardiovascular changes elicited by CIH. However, the effects of CIH on the central mechanisms regulating sympathetic outflow are not fully elucidated. Our research group has explored the hypothesis that the enhanced sympathetic drive following CIH exposure is, at least in part, dependent on alterations in the respiratory network and its interaction with the sympathetic nervous system. In this report, I discuss the changes in the discharge profile of baseline sympathetic activity in rats exposed to CIH, their association with the generation of active expiration and the interactions between expiratory and sympathetic neurones after CIH conditioning. Together, these findings are consistent with the theory that mechanisms of central respiratory-sympathetic coupling are a novel factor in the development of neurogenic hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

PubMed Central

Hoang, Kimberly B.; Cassar, Isaac R.; Grill, Warren M.; Turner, Dennis A.

2017-01-01

The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms. PMID:29066947

Hormone-mediated maternal effects in birds: mechanisms matter but what do we know of them?

PubMed

Groothuis, Ton G G; Schwabl, Hubert

2008-05-12

Over the past decade, birds have proven to be excellent models to study hormone-mediated maternal effects in an evolutionary framework. Almost all these studies focus on the function of maternal steroid hormones for offspring development, but lack of knowledge about the underlying mechanisms hampers further progress. We discuss several hypotheses concerning these mechanisms, point out their relevance for ecological and evolutionary interpretations, and review the relevant data. We first examine whether maternal hormones can accumulate in the egg independently of changes in hormone concentrations in the maternal circulation. This is important for Darwinian selection and female physiological trade-offs, and possible mechanisms for hormone accumulation in the egg, which may differ among hormones, are reviewed. Although independent regulation of plasma and yolk concentrations of hormones is conceivable, the data are as yet inconclusive for ovarian hormones. Next, we discuss embryonic utilization of maternal steroids, since enzyme and receptor systems in the embryo may have coevolved with maternal effect mechanisms in the mother. We consider dose-response relationships and action pathways of androgens and argue that these considerations may help to explain the apparent lack of interference of maternal steroids with sexual differentiation. Finally, we discuss mechanisms underlying the pleiotropic actions of maternal steroids, since linked effects may influence the coevolution of parent and offspring traits, owing to their role in the mediation of physiological trade-offs. Possible mechanisms here are interactions with other hormonal systems in the embryo. We urge endocrinologists to embark on suggested mechanistic studies and behavioural ecologists to adjust their interpretations to accommodate the current knowledge of mechanisms.

Temperature Effects on Kinetics of KV11.1 Drug Block Have Important Consequences for In Silico Proarrhythmic Risk Prediction.

PubMed

Windley, Monique J; Mann, Stefan A; Vandenberg, Jamie I; Hill, Adam P

2016-07-01

Drug block of voltage-gated potassium channel subtype 11.1 human ether-a-go-go related gene (Kv11.1) (hERG) channels, encoded by the KCNH2 gene, is associated with reduced repolarization of the cardiac action potential and is the predominant cause of acquired long QT syndrome that can lead to fatal cardiac arrhythmias. Current safety guidelines require that potency of KV11.1 block is assessed in the preclinical phase of drug development. However, not all drugs that block KV11.1 are proarrhythmic, meaning that screening on the basis of equilibrium measures of block can result in high attrition of potentially low-risk drugs. The basis of the next generation of drug-screening approaches is set to be in silico risk prediction, informed by in vitro mechanistic descriptions of drug binding, including measures of the kinetics of block. A critical issue in this regard is characterizing the temperature dependence of drug binding. Specifically, it is important to address whether kinetics relevant to physiologic temperatures can be inferred or extrapolated from in vitro data gathered at room temperature in high-throughout systems. Here we present the first complete study of the temperature-dependent kinetics of block and unblock of a proarrhythmic drug, cisapride, to KV11.1. Our data highlight a complexity to binding that manifests at higher temperatures and can be explained by accumulation of an intermediate, non-blocking encounter-complex. These results suggest that for cisapride, physiologically relevant kinetic parameters cannot be simply extrapolated from those measured at lower temperatures; rather, data gathered at physiologic temperatures should be used to constrain in silico models that may be used for proarrhythmic risk prediction. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

A modified physiological BCS for prediction of intestinal absorption in drug discovery.

PubMed

Zaki, Noha M; Artursson, Per; Bergström, Christel A S

2010-10-04

In this study, the influence of physiologically relevant media on the compound position in a biopharmaceutical classification system (BCS) which resembled the intestinal absorption was investigated. Both solubility and permeability limited compounds (n = 22) were included to analyze the importance of each of these on the final absorption. Solubility was determined in three different dissolution media, phosphate buffer pH 6.5 (PhB 6.5), fasted state simulated intestinal fluid (FaSSIF), and fed state simulated intestinal fluid (FeSSIF) at 37 °C, and permeability values were determined using the 2/4/A1 cell line. The solubility data and membrane permeability values were used for sorting the compounds into a BCS modified to reflect the fasted and fed state. Three of the seven compounds sorted as BCS II in PhB 6.5 (high permeability, low solubility) changed their position to BCS I when dissolved in FaSSIF and/or FeSSIF (high permeability, high solubility). These were low dosed (20 mg or less) lipophilic molecules displaying solvation limited solubility. In contrast, compounds having solid-state limited solubility had a minor increase in solubility when dissolved in FaSSIF and/or FeSSIF. Although further studies are needed to enable general cutoff values, our study indicates that low dosed BCS Class II compounds which have solubility normally restricted by poor solvation may behave as BCS Class I compounds in vivo. The large series of compounds investigated herein reveals the importance of investigating solubility and dissolution under physiologically relevant conditions in all stages of the drug discovery process to push suitable compounds forward, to select proper formulations, and to reduce the risk of food effects.

AMMO-Prot: amine system project 3D-model finder.

PubMed

Navas-Delgado, Ismael; Montañez, Raúl; Pino-Angeles, Almudena; Moya-García, Aurelio A; Urdiales, José Luis; Sánchez-Jiménez, Francisca; Aldana-Montes, José F

2008-04-25

Amines are biogenic amino acid derivatives, which play pleiotropic and very important yet complex roles in animal physiology. For many other relevant biomolecules, biochemical and molecular data are being accumulated, which need to be integrated in order to be effective in the advance of biological knowledge in the field. For this purpose, a multidisciplinary group has started an ontology-based system named the Amine System Project (ASP) for which amine-related information is the validation bench. In this paper, we describe the Ontology-Based Mediator developed in the Amine System Project (http://asp.uma.es) using the infrastructure of Semantic Directories, and how this system has been used to solve a case related to amine metabolism-related protein structures. This infrastructure is used to publish and manage not only ontologies and their relationships, but also metadata relating to the resources committed with the ontologies. The system developed is available at http://asp.uma.es/WebMediator.

Advances in bioresponsive closed-loop drug delivery systems.

PubMed

Yu, Jicheng; Zhang, Yuqi; Yan, Junjie; Kahkoska, Anna R; Gu, Zhen

2017-11-27

Controlled drug delivery systems are able to improve efficacy and safety of therapeutics by optimizing the duration and kinetics of release. Among them, closed-loop delivery strategies, also known as self-regulated administration, have proven to be a practical tool for homeostatic regulation, by tuning drug release as a function of biosignals relevant to physiological and pathological processes. A typical example is glucose-responsive insulin delivery system, which can mimic the pancreatic beta cells to release insulin with a proper dose at a proper time point by responding to plasma glucose levels. Similar self-regulated systems are also important in the treatment of other diseases including thrombosis and bacterial infection. In this review, we survey the recent advances in bioresponsive closed-loop drug delivery systems, including glucose-responsive, enzyme-activated, and other biosignal-mediated delivery systems. We also discuss the future opportunities and challenges in this field. Copyright © 2017 Elsevier B.V. All rights reserved.

Overcoming the challenges of studying conservation physiology in large whales: a review of available methods

PubMed Central

Hunt, Kathleen E.; Moore, Michael J.; Rolland, Rosalind M.; Kellar, Nicholas M.; Hall, Ailsa J.; Kershaw, Joanna; Raverty, Stephen A.; Davis, Cristina E.; Yeates, Laura C.; Fauquier, Deborah A.; Rowles, Teresa K.; Kraus, Scott D.

2013-01-01

Large whales are subjected to a variety of conservation pressures that could be better monitored and managed if physiological information could be gathered readily from free-swimming whales. However, traditional approaches to studying physiology have been impractical for large whales, because there is no routine method for capture of the largest species and there is presently no practical method of obtaining blood samples from free-swimming whales. We review the currently available techniques for gathering physiological information on large whales using a variety of non-lethal and minimally invasive (or non-invasive) sample matrices. We focus on methods that should produce information relevant to conservation physiology, e.g. measures relevant to stress physiology, reproductive status, nutritional status, immune response, health, and disease. The following four types of samples are discussed: faecal samples, respiratory samples (‘blow’), skin/blubber samples, and photographs. Faecal samples have historically been used for diet analysis but increasingly are also used for hormonal analyses, as well as for assessment of exposure to toxins, pollutants, and parasites. Blow samples contain many hormones as well as respiratory microbes, a diverse array of metabolites, and a variety of immune-related substances. Biopsy dart samples are widely used for genetic, contaminant, and fatty-acid analyses and are now being used for endocrine studies along with proteomic and transcriptomic approaches. Photographic analyses have benefited from recently developed quantitative techniques allowing assessment of skin condition, ectoparasite load, and nutritional status, along with wounds and scars from ship strikes and fishing gear entanglement. Field application of these techniques has the potential to improve our understanding of the physiology of large whales greatly, better enabling assessment of the relative impacts of many anthropogenic and ecological pressures. PMID:27293590

Stress and the psyche-brain-immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review.

PubMed

Bottaccioli, Anna Giulia; Bottaccioli, Francesco; Minelli, Andrea

2018-05-15

In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases. © 2018 New York Academy of Sciences.

The clock is ticking. Ageing of the circadian system: From physiology to cell cycle.

PubMed

Terzibasi-Tozzini, Eva; Martinez-Nicolas, Antonio; Lucas-Sánchez, Alejandro

2017-10-01

The circadian system is the responsible to organise the internal temporal order in relation to the environment of every process of the organisms producing the circadian rhythms. These rhythms have a fixed phase relationship among them and with the environment in order to optimise the available energy and resources. From a cellular level, circadian rhythms are controlled by genetic positive and negative auto-regulated transcriptional and translational feedback loops, which generate 24h rhythms in mRNA and protein levels of the clock components. It has been described about 10% of the genome is controlled by clock genes, with special relevance, due to its implications, to the cell cycle. Ageing is a deleterious process which affects all the organisms' structures including circadian system. The circadian system's ageing may produce a disorganisation among the circadian rhythms, arrhythmicity and, even, disconnection from the environment, resulting in a detrimental situation to the organism. In addition, some environmental conditions can produce circadian disruption, also called chronodisruption, which may produce many pathologies including accelerated ageing. Finally, some strategies to prevent, palliate or counteract chronodisruption effects have been proposed to enhance the circadian system, also called chronoenhancement. This review tries to gather recent advances in the chronobiology of the ageing process, including cell cycle, neurogenesis process and physiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Resistant starch: a promising dietary agent for the prevention/treatment of inflammatory bowel disease and bowel cancer.

PubMed

Higgins, Janine A; Brown, Ian L

2013-03-01

Resistant starch represents a diverse range of indigestible starch-based dietary carbohydrates. Resistant starch has been investigated in the past for its effects on bowel health (pH, epithelial thickness, and apoptosis of colorectal cancer cells); reduction in postprandial glycemia; increased insulin sensitivity; and effects on the gut microbiome. This review highlights advances as resistant starch gains clinical relevance as a potential treatment/preventive tool for diseases such as colorectal cancer (CRC) and diabetes. Recent articles have evaluated the comparative physiological effects of different types of resistant starch and investigated the effects of resistant starch on blood lipids, body weight, and defining resistant starch-induced changes to the micriobiome that may be important in health and disease. The most novel and relevant recent data describe a role for resistant starch in ameliorating inflammation; the use of resistant starch for optimal bowel health and prevention of CRC; and, further, that the systemic effects of resistant starch may be important for the treatment of other forms of cancer, such as breast cancer. This review describes advances in resistant starch research highlighting the gastrointestinal effects that are now being linked to systemic, whole body effects with clinical relevance. These effects have important implications for overall health and the prevention or amelioration of various chronic diseases.

Validation of the i-STAT and HemoCue systems for the analysis of blood parameters in the bar-headed goose, Anser indicus

PubMed Central

Harter, T. S.; Reichert, M.; Brauner, C. J.; Milsom, W. K.

2015-01-01

Every year, bar-headed geese (Anser indicus) perform some of the most remarkable trans-Himalayan migrations, and researchers are increasingly interested in understanding the physiology underlying their high-altitude flight performance. A major challenge is generating reliable measurements of blood parameters on wild birds in the field, where established analytical techniques are often not available. Therefore, we validated two commonly used portable clinical analysers (PCAs), the i-STAT and the HemoCue systems, for the analysis of blood parameters in bar-headed geese. The pH, partial pressures of O2 and CO2 (PO2 and PCO2), haemoglobin O2 saturation (sO2), haematocrit (Hct) and haemoglobin concentration [Hb] were simultaneously measured with the two PCA systems (i-STAT for all parameters; HemoCue for [Hb]) and with conventional laboratory techniques over a physiological range of PO2, PCO2 and Hct. Our results indicate that the i-STAT system can generate reliable values on bar-headed goose whole blood pH, PO2, PCO2 and Hct, but we recommend correcting the obtained values using the linear equations determined here for higher accuracy. The i-STAT is probably not able to produce meaningful measurements of sO2 and [Hb] over a range of physiologically relevant environmental conditions. However, we can recommend the use of the HemoCue to measure [Hb] in the bar-headed goose, if results are corrected. We emphasize that the equations that we provide to correct PCA results are applicable only to bar-headed goose whole blood under the conditions that we tested. We encourage researchers to validate i-STAT or HemoCue results thoroughly for their specific study conditions and species in order to yield accurate results. PMID:27293706

USSR Space Life Sciences Digest, issue 15

NASA Technical Reports Server (NTRS)

Hooke, Lydia Razran (Editor); Teeter, Ronald (Editor); Garshnek, Victoria (Editor); Rowe, Joseph (Editor)

1988-01-01

This is the 15th issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 59 papers published in Russian language periodicals or presented at conferences and of two new Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. An additional feature is a review of a conference devoted to the physiology of extreme states. The abstracts included in this issue have been identified as relevant to 29 areas of space biology and medicine. These areas are adaptation, biological rhythms, biospherics, body fluids, botany, cardiovascular and respiratory systems, endocrinology, enzymology, equipment and instrumentation, exobiology, genetics, habitability and environment effects, human performance, immunology, life support systems, mathematical modeling, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, operational medicine, perception. personnel selection, psychology, radiobiology, reproductive biology, and space biology and medicine.

Autonomic and inflammatory consequences of posttraumatic stress disorder and the link to cardiovascular disease.

PubMed

Brudey, Chevelle; Park, Jeanie; Wiaderkiewicz, Jan; Kobayashi, Ihori; Mellman, Thomas A; Marvar, Paul J

2015-08-15

Stress- and anxiety-related disorders are on the rise in both military and general populations. Over the next decade, it is predicted that treatment of these conditions, in particular, posttraumatic stress disorder (PTSD), along with its associated long-term comorbidities, will challenge the health care system. Multiple organ systems are adversely affected by PTSD, and PTSD is linked to cancer, arthritis, digestive disease, and cardiovascular disease. Evidence for a strong link between PTSD and cardiovascular disease is compelling, and this review describes current clinical data linking PTSD to cardiovascular disease, via inflammation, autonomic dysfunction, and the renin-angiotensin system. Recent clinical and preclinical evidence regarding the role of the renin-angiotensin system in the extinction of fear memory and relevance in PTSD-related immune and autonomic dysfunction is also addressed. Copyright © 2015 the American Physiological Society.

CO2-O2 interactions in extension of tolerance to acute hypoxia

NASA Technical Reports Server (NTRS)

Lambertsen, C. J.

1995-01-01

Objectives and results of experimental projects a re summarized. The scope of information desired included (1) physiological and performance consequences of exposures to simulated microgravity, in rest and graded physical activity, (2) separate influences of graded degrees of atmospheric hypercapnia and hypoxia, and (3) composite effects of hypoxia and hypercapnia. The research objectives were selected for close relevance to existing quantitative information concerning interactions of hypercapnia and hypoxia on respiratory and brain circulatory control. They include: (1) to determine influences of normoxic immersion on interrelations of pulmonary ventilation, arterial PCO2 and PO2, and brain blood flow, in rest and physical work; (2) to determine influence of normoxic immersion on respiratory reactivity to atmospheric hypercapnia at rest; (3) to determine influence of atmospheric hypoxia on respiratory reactivity to hypercapnia at rest and in work; and (4) to provide physiological baselines of data concerning adaptations in acute exposures to aid in investigation of rates of adaptation or deteriorations in physiological or performance capability during subsequent multi-day exposures. A list of publications related to the present grant period is included along with an appendix describing the Performance Measurement System (human perceptual, cognitive and psychomotor functions).

Obesity and drug pharmacology: a review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters.

PubMed

Smit, Cornelis; De Hoogd, Sjoerd; Brüggemann, Roger J M; Knibbe, Catherijne A J

2018-03-01

The rising prevalence of obesity confronts clinicians with dosing problems in the (extreme) overweight population. Obesity has a great impact on key organs that play a role in the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, however the ultimate impact of these changes on how to adapt the dose may not always be known. Areas covered: In this review, physiological changes associated with obesity are discussed. An overview is provided on the alterations in absorption, distribution, drug metabolism and clearance in (morbid) obesity focusing on general principles that can be extracted from pharmacokinetic studies. Also, relevant pharmacodynamic considerations in obesity are discussed. Expert opinion: Over the last two decades, increased knowledge is generated on PK and PD in obesity. Future research should focus on filling in the knowledge gaps that remain, especially in connecting obesity-related physiological changes with changes in PK and/or PD and vice versa. Ultimately, this knowledge can be used to develop physiologically based PK and PD models on the basis of quantitative systems pharmacology principles. Moreover, efforts should focus on thorough prospective evaluation of developed model-based doses with subsequent implementation of these dosing recommendations in clinical practice.

Research on Infancy of Special Relevance for Mental Health. Matrix No. 11A.

ERIC Educational Resources Information Center

Provence, Sally

Research relevant to planning and practice in the area of infant mental health is discussed in this paper. First, three examples of research approaches that reflect current attitudes are given. The first example represents those studies in which there is an effort to closely coordinate physiological and behavioral studies. The second example…

Sleep mechanisms: Sleep deprivation and detection of changing levels of consciousness

NASA Technical Reports Server (NTRS)

Dement, W. C.; Barchas, J. D.

1972-01-01

An attempt was made to obtain information relevant to assessing the need to sleep and make up for lost sleep. Physiological and behavioral parameters were used as measuring parameters. Sleep deprivation in a restricted environment, derivation of data relevant to determining sleepiness from EEG, and the development of the Sanford Sleepiness Scale were discussed.

Pharmacology, signaling and physiological relevance of the G protein-coupled receptor 55.

PubMed

Balenga, Nariman A B; Henstridge, Christopher M; Kargl, Julia; Waldhoer, Maria

2011-01-01

According to The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), ∼70 million European adults have consumed cannabis on at least one occasion. Cannabis consumption leads to a variety of psychoactive effects due to the presence of the constituent Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Δ(9)-THC interacts with the endocannabinoid system (ECS), which consists of the seven transmembrane spanning (7TM)/G protein-coupled receptors (GPCRs) CB(1) and CB(2), their respective ligands (endocannabinoids), and enzymes involved in their biosynthesis and degradation. This system plays a critical role in many physiological processes such as learning and memory, appetite control, pain sensation, motor coordination, lipogenesis, modulation of immune response, and the regulation of bone mass. Therefore, a huge effort has been spent trying to fully elucidate the composition and function of the ECS. The G protein-coupled receptor 55 (GPR55) was recently proposed as a novel component of this system; however, its classification as a cannabinoid receptor has been significantly hampered by its complex pharmacology, signaling, and cellular function. GPR55 is phylogenetically distinct from the traditional cannabinoid receptors, but in some experimental paradigms, it is activated by endocannabinoids, phytocannabinoids, and synthetic cannabinoid ligands. However, the most potent compound appears to be a lysophospholipid known as lysophosphatidylinositol (LPI). Here, we provide a comprehensive evaluation of the current pharmacology and signaling of GPR55 and review the proposed role of this receptor in a number of physiological and pathophysiological processes. Copyright © 2011 Elsevier Inc. All rights reserved.

Electrophysiology Meets Ecology: Investigating How Vision is Tuned to the Life Style of an Animal using Electroretinography.

PubMed

Stowasser, Annette; Mohr, Sarah; Buschbeck, Elke; Vilinsky, Ilya

2015-01-01

Students learn best when projects are multidisciplinary, hands-on, and provide ample opportunity for self-driven investigation. We present a teaching unit that leads students to explore relationships between sensory function and ecology. Field studies, which are rare in neurobiology education, are combined with laboratory experiments that assess visual properties of insect eyes, using electroretinography (ERG). Comprised of nearly one million species, insects are a diverse group of animals, living in nearly all habitats and ecological niches. Each of these lifestyles puts different demands on their visual systems, and accordingly, insects display a wide array of eye organizations and specializations. Physiologically relevant differences can be measured using relatively simple extracellular electrophysiological methods that can be carried out with standard equipment, much of which is already in place in most physiology laboratories. The teaching unit takes advantage of the large pool of locally available species, some of which likely show specialized visual properties that can be measured by students. In the course of the experiments, students collect local insects or other arthropods of their choice, are guided to formulate hypotheses about how the visual system of "their" insects might be tuned to the lifestyle of the species, and use ERGs to investigate the insects' visual response dynamics, and both chromatic and temporal properties of the visual system. Students are then guided to interpret their results in both a comparative physiological and ecological context. This set of experiments closely mirrors authentic research and has proven to be a popular, informative and highly engaging teaching tool.

Electrophysiology Meets Ecology: Investigating How Vision is Tuned to the Life Style of an Animal using Electroretinography

PubMed Central

Stowasser, Annette; Mohr, Sarah; Buschbeck, Elke; Vilinsky, Ilya

2015-01-01

Students learn best when projects are multidisciplinary, hands-on, and provide ample opportunity for self-driven investigation. We present a teaching unit that leads students to explore relationships between sensory function and ecology. Field studies, which are rare in neurobiology education, are combined with laboratory experiments that assess visual properties of insect eyes, using electroretinography (ERG). Comprised of nearly one million species, insects are a diverse group of animals, living in nearly all habitats and ecological niches. Each of these lifestyles puts different demands on their visual systems, and accordingly, insects display a wide array of eye organizations and specializations. Physiologically relevant differences can be measured using relatively simple extracellular electrophysiological methods that can be carried out with standard equipment, much of which is already in place in most physiology laboratories. The teaching unit takes advantage of the large pool of locally available species, some of which likely show specialized visual properties that can be measured by students. In the course of the experiments, students collect local insects or other arthropods of their choice, are guided to formulate hypotheses about how the visual system of “their” insects might be tuned to the lifestyle of the species, and use ERGs to investigate the insects’ visual response dynamics, and both chromatic and temporal properties of the visual system. Students are then guided to interpret their results in both a comparative physiological and ecological context. This set of experiments closely mirrors authentic research and has proven to be a popular, informative and highly engaging teaching tool. PMID:26240534

Managing fatigue in operational settings. 1: Physiological considerations and countermeasures

NASA Technical Reports Server (NTRS)

Rosekind, M. R.; Gander, P. H.; Gregory, K. B.; Smith, R. M.; Miller, D. L.; Oyung, R.; Webbon, L. L.; Johnson, J. M.

1996-01-01

The authors consider three aspects of managing fatigue in the workplace. They provide a brief overview of important scientific findings related to sleep and circadian physiology that establish the psychobiological foundation of fatigue. Their major focus is on the relevance of these findings to operational settings. In addition, they provide examples to describe practical fatigue countermeasures that can be used in operational settings.

No Evidence for Emotional Empathy in Chickens Observing Familiar Adult Conspecifics

PubMed Central

Edgar, Joanne L.; Paul, Elizabeth S.; Harris, Lauren; Penturn, Sarah; Nicol, Christine J.

2012-01-01

The capacity of animals to empathise is of high potential relevance to the welfare of group-housed domestic animals. Emotional empathy is a multifaceted and multilayered phenomenon which ranges from relatively simple processes such as emotional matching behaviour to more complex processes involving interaction between emotional and cognitive perspective taking systems. Our previous research has demonstrated that hens show clear behavioural and physiological responses to the mild distress of their chicks. To investigate whether this capacity exists outside the mother/offspring bond, we conducted a similar experiment in which domestic hens were exposed to the mild distress of unrelated, but familiar adult conspecifics. Each observer hen was exposed to two replicates of four conditions, in counterbalanced order; control (C); control with noise of air puff (CN); air puff to conspecific hen (APC); air puff to observer hen (APH). During each test, the observer hens' behaviour and physiology were measured throughout a 10 min pre-treatment and a 10 min treatment period. Despite showing signs of distress in response to an aversive stimulus directed at themselves (APH), and using methodology sufficiently sensitive to detect empathy-like responses previously, observer hens showed no behavioural or physiological responses to the mild distress of a familiar adult conspecific. The lack of behavioural and physiological response indicates that hens show no basis for emotional empathy in this context. PMID:22348100

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

NASA Astrophysics Data System (ADS)

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-05-01

Within the framework of `Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization

NASA Astrophysics Data System (ADS)

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-05-01

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting molecules within a crowded microenvironment. The excluded volume effect (arising from crowding) increases the effective concentration of actin, which increases the reaction rate, while the microviscosity does not increase sufficiently to lower the reaction rate. This study reveals finer details about the mechanism of MMC.

Macromolecular crowding gives rise to microviscosity, anomalous diffusion and accelerated actin polymerization.

PubMed

Rashid, Rafi; Chee, Stella Min Ling; Raghunath, Michael; Wohland, Thorsten

2015-04-30

Macromolecular crowding (MMC) has been used in various in vitro experimental systems to mimic in vivo physiology. This is because the crowded cytoplasm of cells contains many different types of solutes dissolved in an aqueous medium. MMC in the extracellular microenvironment is involved in maintaining stem cells in their undifferentiated state (niche) as well as in aiding their differentiation after they have travelled to new locations outside the niche. MMC at physiologically relevant fractional volume occupancies (FVOs) significantly enhances the adipogenic differentiation of human bone marrow-derived mesenchymal stem cells during chemically induced adipogenesis. The mechanism by which MMC produces this enhancement is not entirely known. In the context of extracellular collagen deposition, we have recently reported the importance of optimizing the FVO while minimizing the bulk viscosity. Two opposing properties will determine the net rate of a biochemical reaction: the negative effect of bulk viscosity and the positive effect of the excluded volume, the latter being expressed by the FVO. In this study we have looked more closely at the effect of viscosity on reaction rates. We have used fluorimetry to measure the rate of actin polymerization and fluorescence correlation spectroscopy (FCS) to measure diffusion of various probes in solutions containing the crowder Ficoll at physiological concentrations. Similar to its effect on collagen, Ficoll enhanced the actin polymerization rate despite increasing the bulk viscosity. Our FCS measurements reveal a relatively minor component of anomalous diffusion. In addition, our measurements do suggest that microviscosity becomes relevant in a crowded environment. We ruled out bulk viscosity as a cause of the rate enhancement by performing the actin polymerization assay in glycerol. These opposite effects of Ficoll and glycerol led us to conclude that microviscosity becomes relevant at the length scale of the reacting molecules within a crowded microenvironment. The excluded volume effect (arising from crowding) increases the effective concentration of actin, which increases the reaction rate, while the microviscosity does not increase sufficiently to lower the reaction rate. This study reveals finer details about the mechanism of MMC.

Neuroendocrine Disruption: More than Hormones are Upset

PubMed Central

Waye, Andrew; Trudeau, Vance L.

2011-01-01

Only a small proportion of the published research on endocrine-disrupting chemicals (EDC) directly examined effects on neuroendocrine processes. There is an expanding body of evidence that anthropogenic chemicals exert effects on neuroendocrine systems and that these changes might impact peripheral organ systems and physiological processes. Neuroendocrine disruption extends the concept of endocrine disruption to include the full breadth of integrative physiology (i.e., more than hormones are upset). Pollutants may also disrupt numerous other neurochemical pathways to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. Several examples are presented in this review, from both vertebrates and invertebrates, illustrating that diverse environmental pollutants including pharmaceuticals, organochlorine pesticides, and industrial contaminants have the potential to disrupt neuroendocrine control mechanisms. While most investigations on EDC are carried out with vertebrate models, an attempt is also made to highlight the importance of research on invertebrate neuroendocrine disruption. The neurophysiology of many invertebrates is well described and many of their neurotransmitters are similar or identical to those in vertebrates; therefore, lessons learned from one group of organisms may help us understand potential adverse effects in others. This review argues for the adoption of systems biology and integrative physiology to address the effects of EDC. Effects of pulp and paper mill effluents on fish reproduction are a good example of where relatively narrow hypothesis testing strategies (e.g., whether or not pollutants are sex steroid mimics) have only partially solved a major problem in environmental biology. It is clear that a global, integrative physiological approach, including improved understanding of neuroendocrine control mechanisms, is warranted to fully understand the impacts of pulp and paper mill effluents. Neuroendocrine disruptors are defined as pollutants in the environment that are capable of acting as agonists/antagonists or modulators of the synthesis and/or metabolism of neuropeptides, neurotransmitters, or neurohormones, which subsequently alter diverse physiological, behavioral, or hormonal processes to affect an animal's capacity to reproduce, develop and grow, or deal with stress and other challenges. By adopting a definition of neuroendocrine disruption that encompasses both direct physiological targets and their indirect downstream effects, from the level of the individual to the ecosystem, a more comprehensive picture of the consequences of environmentally relevant EDC exposure may emerge. PMID:21790312

Cue-reactivity in behavioral addictions: A meta-analysis and methodological considerations.

PubMed

Starcke, Katrin; Antons, Stephanie; Trotzke, Patrick; Brand, Matthias

2018-05-23

Background and aims Recent research has applied cue-reactivity paradigms to behavioral addictions. The aim of the current meta-analysis is to systematically analyze the effects of learning-based cue-reactivity in behavioral addictions. Methods The current meta-analysis includes 18 studies (29 data sets, 510 participants) that have used a cue-reactivity paradigm in persons with gambling (eight studies), gaming (nine studies), or buying (one study) disorders. We compared subjective, peripheral physiological, electroencephal, and neural responses toward addiction-relevant cues in patients versus control participants and toward addiction-relevant cues versus control cues in patients. Results Persons with behavioral addictions showed higher cue-reactivity toward addiction-relevant cues compared with control participants: subjective cue-reactivity (d = 0.84, p = .01) and peripheral physiological and electroencephal measures of cue-reactivity (d = 0.61, p < .01). Increased neural activation was found in the caudate nucleus, inferior frontal gyrus, median cingulate cortex, subgenual cingulate, and precentral gyrus. Persons with gambling, gaming, or buying disorders also showed higher cue-reactivity toward addiction-relevant cues compared with control cues: subjective cue-reactivity (d = 0.39, p = .11) and peripheral physiological and electroencephal measures of cue-reactivity (d = 0.47, p = .05). Increased neural activation was found in the caudate nucleus, inferior frontal gyrus, angular gyrus, inferior network, and precuneus. Discussion and conclusions Cue-reactivity not only exists in substance-use disorders but also in gambling, gaming, and buying disorders. Future research should differentiate between cue-reactivity in addictive behaviors and cue-reactivity in functional excessive behaviors such as passions, hobbies, or professions.

Computational physiology and the Physiome Project.

PubMed

Crampin, Edmund J; Halstead, Matthew; Hunter, Peter; Nielsen, Poul; Noble, Denis; Smith, Nicolas; Tawhai, Merryn

2004-01-01

Bioengineering analyses of physiological systems use the computational solution of physical conservation laws on anatomically detailed geometric models to understand the physiological function of intact organs in terms of the properties and behaviour of the cells and tissues within the organ. By linking behaviour in a quantitative, mathematically defined sense across multiple scales of biological organization--from proteins to cells, tissues, organs and organ systems--these methods have the potential to link patient-specific knowledge at the two ends of these spatial scales. A genetic profile linked to cardiac ion channel mutations, for example, can be interpreted in relation to body surface ECG measurements via a mathematical model of the heart and torso, which includes the spatial distribution of cardiac ion channels throughout the myocardium and the individual kinetics for each of the approximately 50 types of ion channel, exchanger or pump known to be present in the heart. Similarly, linking molecular defects such as mutations of chloride ion channels in lung epithelial cells to the integrated function of the intact lung requires models that include the detailed anatomy of the lungs, the physics of air flow, blood flow and gas exchange, together with the large deformation mechanics of breathing. Organizing this large body of knowledge into a coherent framework for modelling requires the development of ontologies, markup languages for encoding models, and web-accessible distributed databases. In this article we review the state of the field at all the relevant levels, and the tools that are being developed to tackle such complexity. Integrative physiology is central to the interpretation of genomic and proteomic data, and is becoming a highly quantitative, computer-intensive discipline.

The acclimative biogeochemical model of the southern North Sea

NASA Astrophysics Data System (ADS)

Kerimoglu, Onur; Hofmeister, Richard; Maerz, Joeran; Riethmüller, Rolf; Wirtz, Kai W.

2017-10-01

Ecosystem models often rely on heuristic descriptions of autotrophic growth that fail to reproduce various stationary and dynamic states of phytoplankton cellular composition observed in laboratory experiments. Here, we present the integration of an advanced phytoplankton growth model within a coupled three-dimensional physical-biogeochemical model and the application of the model system to the southern North Sea (SNS) defined on a relatively high resolution (˜ 1.5-4.5 km) curvilinear grid. The autotrophic growth model, recently introduced by Wirtz and Kerimoglu (2016), is based on a set of novel concepts for the allocation of internal resources and operation of cellular metabolism. The coupled model system consists of the General Estuarine Transport Model (GETM) as the hydrodynamical driver, a lower-trophic-level model and a simple sediment diagenesis model. We force the model system with realistic atmospheric and riverine fluxes, background turbidity caused by suspended particulate matter (SPM) and open ocean boundary conditions. For a simulation for the period 2000-2010, we show that the model system satisfactorily reproduces the physical and biogeochemical states of the system within the German Bight characterized by steep salinity; nutrient and chlorophyll (Chl) gradients, as inferred from comparisons against observation data from long-term monitoring stations; sparse in situ measurements; continuous transects; and satellites. The model also displays skill in capturing the formation of thin chlorophyll layers at the pycnocline, which is frequently observed within the stratified regions during summer. A sensitivity analysis reveals that the vertical distributions of phytoplankton concentrations estimated by the model can be qualitatively sensitive to the description of the light climate and dependence of sinking rates on the internal nutrient reserves. A non-acclimative (fixed-physiology) version of the model predicted entirely different vertical profiles, suggesting that accounting for physiological flexibility might be relevant for a consistent representation of the vertical distribution of phytoplankton biomass. Our results point to significant variability in the cellular chlorophyll-to-carbon ratio (Chl : C) across seasons and the coastal to offshore transition. Up to 3-fold-higher Chl : C at the coastal areas in comparison to those at the offshore areas contribute to the steepness of the chlorophyll gradient. The model also predicts much higher phytoplankton concentrations at the coastal areas in comparison to its non-acclimative equivalent. Hence, findings of this study provide evidence for the relevance of physiological flexibility, here reflected by spatial and seasonal variations in Chl : C, for a realistic description of biogeochemical fluxes, particularly in the environments displaying strong resource gradients.

Physiological Reactivity in a Community Sample of Sexually Aggressive Young Men: A Test of Competing Hypotheses

PubMed Central

Peterson, Zoë D.; Janssen, Erick; Goodrich, David; Heiman, Julia R.

2015-01-01

Men’s sexually aggressive behavior potentially could relate to either physiological hyporeactivity or hyperreactivity, and these two different physiological profiles could be associated with different underlying causes of sexual aggression. Thus, measurement of physiological reactivity could provide insight into mechanisms relevant to the etiology of sexual aggression. The relationship between sexual aggression and physiological reactivity was investigated in 78 community men (38 sexually aggressive and 40 non-aggressive men). In a laboratory protocol, the men were exposed to neutral, negative-affect-inducing, and positive-affect-inducing stimuli. Men’s salivary cortisol concentrations and electrodermal activity (EDA) were measured throughout the laboratory procedure. Sexually aggressive men demonstrated (1) lower overall cortisol levels and (2) lower EDA reactivity in some conditions as compared to non-aggressive men. Results of this study were consistent with the idea that men’s sexual aggression is associated with physiological hyporeactivity, a physiological profile that has been found to be associated with externalizing behaviors and psychopathic traits. PMID:24310818

Physiological reactivity in a community sample of sexually aggressive young men: a test of competing hypotheses.

PubMed

Peterson, Zoë D; Janssen, Erick; Goodrich, David; Heiman, Julia R

2014-01-01

Men's sexually aggressive behavior potentially could relate to either physiological hyporeactivity or hyperreactivity, and these two different physiological profiles could be associated with different underlying causes of sexual aggression. Thus, measurement of physiological reactivity could provide insight into mechanisms relevant to the etiology of sexual aggression. The relationship between sexual aggression and physiological reactivity was investigated in 78 community men (38 sexually aggressive and 40 non-aggressive men). In a laboratory protocol, the men were exposed to neutral, negative-affect-inducing, and positive-affect-inducing stimuli. Men's salivary cortisol concentrations and electrodermal activity (EDA) were measured throughout the laboratory procedure. Sexually aggressive men demonstrated (1) lower overall cortisol levels and (2) lower EDA reactivity in some conditions as compared to non-aggressive men. Results of this study were consistent with the idea that men's sexual aggression is associated with physiological hyporeactivity, a physiological profile that has been found to be associated with externalizing behaviors and psychopathic traits. © 2013 Wiley Periodicals, Inc.

Developmental programming: the role of growth hormone.

PubMed

Oberbauer, Anita M

2015-01-01

Developmental programming of the fetus has consequences for physiologic responses in the offspring as an adult and, more recently, is implicated in the expression of altered phenotypes of future generations. Some phenotypes, such as fertility, bone strength, and adiposity are highly relevant to food animal production and in utero factors that impinge on those traits are vital to understand. A key systemic regulatory hormone is growth hormone (GH), which has a developmental role in virtually all tissues and organs. This review catalogs the impact of GH on tissue programming and how perturbations early in development influence GH function.

RNAi in the mouse: rapid and affordable gene function studies in a vertebrate system.

PubMed

Rytlewski, Julie A; Beronja, Slobodan

2015-01-01

The addition of RNA interference (RNAi) to the mammalian genomic toolbox has significantly expanded our ability to use higher-order models in studies of development and disease. The mouse, in particular, has benefited most from RNAi technology. Unique combinations of RNAi vectors and delivery methods now offer a broad platform for gene silencing in transgenic mice, enabling the design of new physiologically relevant models. The era of RNAi mice has accelerated the pace of genetic study and made high-throughput screens not only feasible but also affordable. © 2014 Wiley Periodicals, Inc.

Electricity and colloidal stability: how charge distribution in the tissue can affects wound healing.

PubMed

Farber, Paulo Luiz; Hochman, Bernardo; Furtado, Fabianne; Ferreira, Lydia Masako

2014-02-01

The role of endogenous electric fields in wound healing is still not fully understood. Electric fields are of fundamental importance in various biological processes, ranging from embryonic development to disease progression, as described by many investigators in the last century. This hypothesis brings together some relevant literature on the importance of electric fields in physiology and pathology, the theory of biologically closed electric circuits, skin battery (a phenomenon that occurs after skin injury and seems to be involved in tissue repair), the relationship between electric charge and interstitial exclusion, and how skin tissues can be regarded as colloidal systems. The importance of electric charges, as established in the early works on the subject and the relevance of zeta potential and colloid stability are also analyzed, and together bring a new light for the physics involved in the wound repair of all the body tissues. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dynamic optical imaging of vascular and metabolic reactivity in rheumatoid joints.

PubMed

Lasker, Joseph M; Fong, Christopher J; Ginat, Daniel T; Dwyer, Edward; Hielscher, Andreas H

2007-01-01

Dynamic optical imaging is increasingly applied to clinically relevant areas such as brain and cancer imaging. In this approach, some external stimulus is applied and changes in relevant physiological parameters (e.g., oxy- or deoxyhemoglobin concentrations) are determined. The advantage of this approach is that the prestimulus state can be used as a reference or baseline against which the changes can be calibrated. Here we present the first application of this method to the problem of characterizing joint diseases, especially effects of rheumatoid arthritis (RA) in the proximal interphalangeal finger joints. Using a dual-wavelength tomographic imaging system together with previously implemented model-based iterative image reconstruction schemes, we have performed initial dynamic imaging case studies on a limited number of healthy volunteers and patients diagnosed with RA. Focusing on three cases studies, we illustrated our major finds. These studies support our hypothesis that differences in the vascular reactivity exist between affected and unaffected joints.

Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems

PubMed Central

Arnold, Kathryn E.; Brown, A. Ross; Ankley, Gerald T.; Sumpter, John P.

2014-01-01

Global pharmaceutical consumption is rising with the growing and ageing human population and more intensive food production. Recent studies have revealed pharmaceutical residues in a wide range of ecosystems and organisms. Environmental concentrations are often low, but pharmaceuticals typically are designed to have biological effects at low doses, acting on physiological systems that can be evolutionarily conserved across taxa. This Theme Issue introduces the latest research investigating the risks of environmentally relevant concentrations of pharmaceuticals to vertebrate wildlife. We take a holistic, global view of environmental exposure to pharmaceuticals encompassing terrestrial, freshwater and marine ecosystems in high- and low-income countries. Based on both field and laboratory data, the evidence for and relevance of changes to physiology and behaviour, in addition to mortality and reproductive effects, are examined in terms of the population- and community-level consequences of pharmaceutical exposure on wildlife. Studies on uptake, trophic transfer and indirect effects of pharmaceuticals acting via food webs are presented. Given the logistical and ethical complexities of research in this area, several papers focus on techniques for prioritizing which compounds are most likely to harm wildlife and how modelling approaches can make predictions about the bioavailability, metabolism and toxicity of pharmaceuticals in non-target species. This Theme Issue aims to help clarify the uncertainties, highlight opportunities and inform ongoing scientific and policy debates on the impacts of pharmaceuticals in the environment. PMID:25405959

Combined effects of chemical priming and mechanical stimulation on mesenchymal stem cell differentiation on nanofiber scaffolds

PubMed Central

Subramony, Siddarth D.; Su, Amanda; Yeager, Keith; Lu, Helen H.

2014-01-01

Functional tissue engineering of connective tissues such as the anterior cruciate ligament (ACL) remains a significant clinical challenge, largely due to the need for mechanically competent scaffold systems for grafting, as well as a reliable cell source for tissue formation. We have designed an aligned, polylactide-co-glycolide (PLGA) nanofiber-based scaffold with physiologically relevant mechanical properties for ligament regeneration. The objective of this study is to identify optimal tissue engineering strategies for fibroblastic induction of human mesenchymal stem cells (hMSC), testing the hypothesis that basic fibroblast growth factor (bFGF) priming coupled with tensile loading will enhance hMSC-mediated ligament regeneration. It was observed that compared to the unloaded, as well as growth factor-primed but unloaded controls, bFGF stimulation followed by physiologically relevant tensile loading enhanced hMSC proliferation, collagen production and subsequent differentiation into ligament fibroblast-like cells, upregulating the expression of types I and III collagen, as well as tenasin-C and tenomodulin. The results of this study suggest that bFGF priming increases cell proliferation, while mechanical stimulation of the hMSCs on the aligned nanofiber scaffold promotes fibroblastic induction of these cells. In addition to demonstrating the potential of nanofiber scaffolds for hMSC-mediated functional ligament tissue engineering, this study yields new insights into the interactive effects of chemical and mechanical stimuli on stem cell differentiation. PMID:24267271

Modeling the interaction between the intra-aortic balloon pump and the cardiovascular system: the effect of timing.

PubMed

Schampaert, Stéphanie; Rutten, Marcel C M; van T Veer, Marcel; van Nunen, Lokien X; Tonino, Pim A L; Pijls, Nico H J; van de Vosse, Frans N

2013-01-01

Because of the large number of interaction factors involved, the effects of the intra-aortic balloon pump (IABP) have not been investigated deeply. To enhance its clinical efficiency and to better define indications for use, advanced models are required to test the interaction between the IABP and the cardiovascular system. A patient with mild blood pressure depression and a lowered cardiac output is modeled in a lumped parameter computational model, developed with physiologically representative elements for relevant components of circulation and device. IABP support is applied, and the moments of balloon inflation and deflation are varied around their conventional timing modes. For validation purposes, timing is adapted within acceptable ranges in ten patients undergoing IABP therapy for typical clinical indications. In both model and patients, the IABP induces a diastolic blood pressure augmentation as well as a systolic reduction in afterload. The support capabilities of the IABP benefit the most when the balloon is deflated simultaneously with ventricular contraction, whereas inflation before onset of diastole unconditionally interferes with ejection. The physiologic response makes the model an excellent tool for testing the interaction between the IABP and the cardiovascular system, and how alterations of specific IABP parameters (i.e., timing) affect this coupling.

Transport across the choroid plexus epithelium.

PubMed

Praetorius, Jeppe; Damkier, Helle Hasager

2017-06-01

The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

Engineering of a Biomimetic Pericyte-Covered 3D Microvascular Network.

PubMed

Kim, Jaerim; Chung, Minhwan; Kim, Sudong; Jo, Dong Hyun; Kim, Jeong Hun; Jeon, Noo Li

2015-01-01

Pericytes enveloping the endothelium play an important role in the physiology and pathology of microvessels, especially in vessel maturation and stabilization. However, our understanding of fundamental pericyte biology is limited by the lack of a robust in vitro model system that allows researchers to evaluate the interactions among multiple cell types in perfusable blood vessels. The present work describes a microfluidic platform that can be used to investigate interactions between pericytes and endothelial cells (ECs) during the sprouting, growth, and maturation steps of neovessel formation. A mixture of ECs and pericytes was attached to the side of a pre-patterned three dimensional fibrin matrix and allowed to sprout across the matrix. The effects of intact coverage and EC maturation by the pericytes on the perfused EC network were confirmed using a confocal microscope. Compared with EC monoculture conditions, EC-pericyte co-cultured vessels showed a significant reduction in diameter, increased numbers of junctions and branches and decreased permeability. In response to biochemical factors, ECs and pericytes in the platform showed the similar features with previous reports from in vivo experiments, thus reflect various pathophysiological conditions of in vivo microvessels. Taken together, these results support the physiological relevancy of our three-dimensional microfluidic culture system but also that the system can be used to screen drug effect on EC-pericyte biology.

Peptidase inhibitors in tick physiology.

PubMed

Parizi, L F; Ali, A; Tirloni, L; Oldiges, D P; Sabadin, G A; Coutinho, M L; Seixas, A; Logullo, C; Termignoni, C; DA Silva Vaz, I

2018-06-01

Peptidase inhibitors regulate a wide range of physiological processes involved in the interaction between hematophagous parasites and their hosts, including tissue remodeling, the immune response and blood coagulation. In tick physiology, peptidase inhibitors have a crucial role in adaptation to improve parasitism mechanisms, facilitating blood feeding by interfering with defense-related host peptidases. Recently, a larger number of studies on this topic led to the description of several new tick inhibitors displaying interesting novel features, for example a role in pathogen transmission to the host. A comprehensive review discussing these emerging concepts can therefore shed light on peptidase inhibitor functions, their relevance to tick physiology and their potential applications. Here, we summarize and examine the general characteristics, functional diversity and action of tick peptidase inhibitors with known physiological roles in the tick-host-pathogen interaction. © 2017 The Royal Entomological Society.

Influence of the Circadian System on Disease Severity

PubMed Central

Litinski, Mikhail; Scheer, Frank AJL; Shea, Steven A

2009-01-01

Synopsis The severity of many diseases varies across the day and night. For example, adverse cardiovascular incidents peak in the morning, asthma is often worse at night and temporal lobe epileptic seizures are most prevalent in the afternoon. These patterns may be due to the day/night rhythm in environment and behavior, and/or endogenous circadian rhythms in physiology. Furthermore, chronic misalignment between the endogenous circadian timing system and the behavioral cycles could be a cause of increased risk of diabetes, obesity, cardiovascular disease and certain cancers in shift workers. Here we describe the magnitude, relevance and potential biological basis of such daily changes in disease severity and of circadian/behavioral misalignment, and present how these insights may help in the development of appropriate chronotherapy. PMID:20161149

Control mechanisms of circadian rhythms in body composition: Implications for manned spaceflight

NASA Technical Reports Server (NTRS)

Moore-Ede, M. C.

1976-01-01

The mechanisms underlying the internal synchronization of the circadian variations in electrolyte content in body compartments were investigated, and the significance of these oscillations for manned spaceflight were examined. The experiments were performed with a chair-acclimatized squirrel monkey system, in which the animal sits in a chair, restrained only around the waist. The following information was given: (1) experimental methodology description, (2) summary of results obtained during the first contract year, and (3) discussion of the research performed during the second contract year. This included the following topics: physiological mechanisms promoting normal circadian internal synchronization, factors precipitating internal desynchronization, pathophysiological consequences of internal desynchronization of particular relevance to spaceflight, and validation of a chair-acclimatized system.

Supplemental blue LED lighting array to improve the signal quality in hyperspectral imaging of plants.

PubMed

Mahlein, Anne-Katrin; Hammersley, Simon; Oerke, Erich-Christian; Dehne, Heinz-Wilhelm; Goldbach, Heiner; Grieve, Bruce

2015-06-01

Hyperspectral imaging systems used in plant science or agriculture often have suboptimal signal-to-noise ratio in the blue region (400-500 nm) of the electromagnetic spectrum. Typically there are two principal reasons for this effect, the low sensitivity of the imaging sensor and the low amount of light available from the illuminating source. In plant science, the blue region contains relevant information about the physiology and the health status of a plant. We report on the improvement in sensitivity of a hyperspectral imaging system in the blue region of the spectrum by using supplemental illumination provided by an array of high brightness light emitting diodes (LEDs) with an emission peak at 470 nm.

USSR space life sciences digest, issue 27

NASA Technical Reports Server (NTRS)

Stone, Lydia Razran (Editor); Teeter, Ronald (Editor); Garshnek, Victoria (Editor); Rowe, Joseph (Editor)

1990-01-01

This is the twenty-fifth issue of NASA's Space Life Sciences Digest. It contains abstracts of 30 journal papers or book chapters published in Russian and of 2 Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. The abstracts in this issue have been identified as relevant to 18 areas of space biology and medicine. These areas include: adaptation, aviation medicine, biological rhythms, biospherics, botany, cardiovascular and respiratory systems, endocrinology, enzymology, exobiology, habitability and environmental effects, hematology, immunology, metabolism, musculoskeletal system, neurophysiology, radiobiology, and space medicine. A Soviet book review of a British handbook of aviation medicine and a description of the work of the division on aviation and space medicine of the Moscow Physiological Society are also included.

The Behavior-Physiology Nexus: Behavioral and Physiological Compensation Are Relied on to Different Extents between Seasons.

PubMed

Basson, Christine H; Clusella-Trullas, Susana

2015-01-01

Environmental variability occurring at different timescales can significantly reduce performance, resulting in evolutionary fitness costs. Shifts in thermoregulatory behavior, metabolism, and water loss via phenotypic plasticity can compensate for thermal variation, but the relative contribution of each mechanism and how they may influence each other are largely unknown. Here, we take an ecologically relevant experimental approach to dissect these potential responses at two temporal scales: weather transients and seasons. Using acclimation to cold, average, or warm conditions in summer and winter, we measure the direction and magnitude of plasticity of resting metabolic rate (RMR), water loss rate (WLR), and preferred body temperature (Tpref) in the lizard Cordylus oelofseni within and between seasons. In summer, lizards selected lower Tpref when acclimated to warm versus cold but had no plasticity of either RMR or WLR. By contrast, winter lizards showed partial compensation of RMR but no behavioral compensation. Between seasons, both behavioral and physiological shifts took place. By integrating ecological reality into laboratory assays, we demonstrate that behavioral and physiological responses of C. oelofseni can be contrasting, depending on the timescale investigated. Incorporating ecologically relevant scenarios and the plasticity of multiple traits is thus essential when attempting to forecast extinction risk to climate change.

Competition between Visual Events Modulates the Influence of Salience during Free-Viewing of Naturalistic Videos

PubMed Central

Nardo, Davide; Console, Paola; Reverberi, Carlo; Macaluso, Emiliano

2016-01-01

In daily life the brain is exposed to a large amount of external signals that compete for processing resources. The attentional system can select relevant information based on many possible combinations of goal-directed and stimulus-driven control signals. Here, we investigate the behavioral and physiological effects of competition between distinctive visual events during free-viewing of naturalistic videos. Nineteen healthy subjects underwent functional magnetic resonance imaging (fMRI) while viewing short video-clips of everyday life situations, without any explicit goal-directed task. Each video contained either a single semantically-relevant event on the left or right side (Lat-trials), or multiple distinctive events in both hemifields (Multi-trials). For each video, we computed a salience index to quantify the lateralization bias due to stimulus-driven signals, and a gaze index (based on eye-tracking data) to quantify the efficacy of the stimuli in capturing attention to either side. Behaviorally, our results showed that stimulus-driven salience influenced spatial orienting only in presence of multiple competing events (Multi-trials). fMRI results showed that the processing of competing events engaged the ventral attention network, including the right temporoparietal junction (R TPJ) and the right inferior frontal cortex. Salience was found to modulate activity in the visual cortex, but only in the presence of competing events; while the orienting efficacy of Multi-trials affected activity in both the visual cortex and posterior parietal cortex (PPC). We conclude that in presence of multiple competing events, the ventral attention system detects semantically-relevant events, while regions of the dorsal system make use of saliency signals to select relevant locations and guide spatial orienting. PMID:27445760

Evaluation of a computer-based approach to teaching acid/base physiology.

PubMed

Rawson, Richard E; Quinlan, Kathleen M

2002-12-01

Because acid/base physiology is a difficult subject for most medical and veterinary students, the first author designed a software program, Acid/Base Primer, that would help students with this topic. The Acid/Base Primer was designed and evaluated within a conceptual framework of basic educational principles. Seventy-five first-year veterinary students (of 81; 93% response rate) participated in this study. Students took both a pre- and posttest of content understanding. After completing the Acid/Base Primer in pairs, each student filled out a survey evaluating the features of the program and describing his/her use and experience of it. Four pairs of students participated in interviews that elaborated on the surveys. Scores improved from 53 +/- 2% on the pretest to 74 +/- 1% on an immediate posttest. On surveys and in interviews, students reported that the program helped them construct their own understanding of acid/base physiology and prompted discussions in pairs of students when individual understandings differed. The case-based format provided anchors and a high degree of relevance. Repetition of concepts helped students develop a more complex network of understanding. Questions in the program served to scaffold the learning process by providing direction, accentuating the relevant features of the cases, and provoking discussion. Guidelines for software development were generated on the basis of the findings and relevant educational literature.

A conceptual framework for homeostasis: development and validation.

PubMed

McFarland, Jenny; Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

2016-06-01

We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. Copyright © 2016 The American Physiological Society.

Ecosystems Biology Approaches To Determine Key Fitness Traits of Soil Microorganisms

NASA Astrophysics Data System (ADS)

Brodie, E.; Zhalnina, K.; Karaoz, U.; Cho, H.; Nuccio, E. E.; Shi, S.; Lipton, M. S.; Zhou, J.; Pett-Ridge, J.; Northen, T.; Firestone, M.

2014-12-01

The application of theoretical approaches such as trait-based modeling represent powerful tools to explain and perhaps predict complex patterns in microbial distribution and function across environmental gradients in space and time. These models are mostly deterministic and where available are built upon a detailed understanding of microbial physiology and response to environmental factors. However as most soil microorganisms have not been cultivated, for the majority our understanding is limited to insights from environmental 'omic information. Information gleaned from 'omic studies of complex systems should be regarded as providing hypotheses, and these hypotheses should be tested under controlled laboratory conditions if they are to be propagated into deterministic models. In a semi-arid Mediterranean grassland system we are attempting to dissect microbial communities into functional guilds with defined physiological traits and are using a range of 'omics approaches to characterize their metabolic potential and niche preference. Initially, two physiologically relevant time points (peak plant activity and prior to wet-up) were sampled and metagenomes sequenced deeply (600-900 Gbp). Following assembly, differential coverage and nucleotide frequency binning were carried out to yield draft genomes. In addition, using a range of cultivation media we have isolated a broad range of bacteria representing abundant bacterial genotypes and with genome sequences of almost 40 isolates are testing genomic predictions regarding growth rate, temperature and substrate utilization in vitro. This presentation will discuss the opportunities and challenges in parameterizing microbial functional guilds from environmental 'omic information for use in trait-based models.

Physiologically Based Pharmacokinetic and Absorption Modeling for Osmotic Pump Products.

PubMed

Ni, Zhanglin; Talattof, Arjang; Fan, Jianghong; Tsakalozou, Eleftheria; Sharan, Satish; Sun, Dajun; Wen, Hong; Zhao, Liang; Zhang, Xinyuan

2017-07-01

Physiologically based pharmacokinetic (PBPK) and absorption modeling approaches were employed for oral extended-release (ER) drug products based on an osmotic drug delivery system (osmotic pumps). The purpose was to systemically evaluate the in vivo relevance of in vitro dissolution for this type of formulation. As expected, in vitro dissolution appeared to be generally predictive of in vivo PK profiles, because of the unique feature of this delivery system that the in vitro and in vivo release of osmotic pump drug products is less susceptible to surrounding environment in the gastrointestinal (GI) tract such as pH, hydrodynamic, and food effects. The present study considered BCS (Biopharmaceutics Classification System) class 1, 2, and 3 drug products with half-lives ranging from 2 to greater than 24 h. In some cases, the colonic absorption models needed to be adjusted to account for absorption in the colon. C max (maximum plasma concentration) and AUCt (area under the concentration curve) of the studied drug products were sensitive to changes in colon permeability and segmental GI transit times in a drug product-dependent manner. While improvement of the methodology is still warranted for more precise prediction (e.g., colonic absorption and dynamic movement in the GI tract), the results from the present study further emphasized the advantage of using PBPK modeling in addressing product-specific questions arising from regulatory review and drug development.

Ethyl nitrite is produced in the human stomach from dietary nitrate and ethanol, releasing nitric oxide at physiological pH: potential impact on gastric motility.

PubMed

Rocha, Bárbara S; Gago, Bruno; Barbosa, Rui M; Cavaleiro, Carlos; Laranjinha, João

2015-05-01

Nitric oxide ((∙)NO), a ubiquitous molecule involved in a plethora of signaling pathways, is produced from dietary nitrate in the gut through the so-called nitrate-nitrite-NO pathway. In the stomach, nitrite derived from dietary nitrate triggers a network of chemical reactions targeting endogenous and exogenous biomolecules, thereby producing new compounds with physiological activity. The aim of this study was to ascertain whether compounds with physiological relevance are produced in the stomach upon consumption of nitrate- and ethanol-rich foods. Human volunteers consumed a serving of lettuce (source of nitrate) and alcoholic beverages (source of ethanol). After 15 min, samples of the gastric headspace were collected and ethyl nitrite was identified by GC-MS. Wistar rats were used to study the impact of ethyl nitrite on gastric smooth muscle relaxation at physiological pH. Nitrogen oxides, produced from nitrite in the stomach, induce nitrosation of ethanol from alcoholic beverages in the human stomach yielding ethyl nitrite. Ethyl nitrite, a potent vasodilator, is produced in vivo upon the consumption of lettuce with either red wine or whisky. Moreover, at physiological pH, ethyl nitrite induces gastric smooth muscle relaxation through a cGMP-dependent pathway. Overall, these results suggest that ethyl nitrite is produced in the gastric lumen and releases (∙)NO at physiological pH, which ultimately may have an impact on gastric motility. Systemic effects may also be expected if ethyl nitrite diffuses through the gastric mucosa reaching blood vessels, therefore operating as a (∙)NO carrier throughout the body. These data pinpoint posttranslational modifications as an underappreciated mechanism for the production of novel molecules with physiological impact locally in the gut and highlight the notion that diet may fuel compounds with the potential to modulate gastrointestinal welfare. Copyright © 2015 Elsevier Inc. All rights reserved.

[Musculoskeletal pain].

PubMed

Casser, H-R; Schaible, H-G

2015-10-01

Among the clinically relevant pain conditions, pain in the musculoskeletal system is most frequent. This article reports extensive epidemiological data on musculoskeletal system pain in Germany and worldwide. Since back pain is most frequent, the diagnostics and therapeutic algorithms of acute, recurring, and chronic lower back pain in Germany will be particularly addressed. The importance of the physiologic-organic, the cognitive-emotional, the behavioral, and the social level to diagnostics and treatment will be discussed. We will also focus on osteoarthritic pain and address its epidemiology, clinical importance, and significance for the health care system. This article will list some reasons why the musculoskeletal system in particular is frequently the site of chronic pain. The authors believe that these reasons are to be sought in the complex structures of the musculoskeletal system; in the particular sensitivity of the deep somatic nociceptive system for long-term sensitization processes, as well as the ensuing nervous system reactions; and in the interactions between the nervous and immune systems. The article will give some insights into the research carried out on this topic in Germany.

[Efflux systems in Serratia marcescens].

PubMed

Mardanova, A M; Bogomol'naia, L M; Romanova, Iu D; Sharipova, M R

2014-01-01

A widespread bacterium Serratia marcescens (family Enterobacteriaceae) is an opportunistic and exhibits multiple drug resistance. Active removal of antibiotics and other antimicrobials from pathogen and exhibits multiple drug resistance. Active removal of antibiotics and other antimicrobials from the cells by efflux systems is one of the mechanisms responsible for microbial resistance to these compounds. Among enterobacteria, efflux systems of Escherichia coli and Salmonella enterica var. Typhimurium have been studied most extensively. Few efflux systems that belong to different families have been reported for S. marcescens. In this review, we analyzed available literature about S. marcescens efflux systems and carried out the comparative analysis of the genes encoding the RND type systems in different Serratia species and in other enterobacteria. Bioinformatical analysis of the S. marcescens genome allowed us to identify the previously unknown efflux systems based on their homology with the relevant E. coli genes. Identification of additional efflux systems in S. marcescens genome will promote our understanding of physiology of these bacteria, will detect new molecular mechanisms of resistance and will reveal their resistance potential.

“Do-it-yourself in vitro vasculature that recapitulates in vivo geometries for investigating endothelial-blood cell interactions”

PubMed Central

Mannino, Robert G.; Myers, David R.; Ahn, Byungwook; Wang, Yichen; Margo Rollins; Gole, Hope; Lin, Angela S.; Guldberg, Robert E.; Giddens, Don P.; Timmins, Lucas H.; Lam, Wilbur A.

2015-01-01

Investigating biophysical cellular interactions in the circulation currently requires choosing between in vivo models, which are difficult to interpret due in part to the hemodynamic and geometric complexities of the vasculature; or in vitro systems, which suffer from non-physiologic assumptions and/or require specialized microfabrication facilities and expertise. To bridge that gap, we developed an in vitro “do-it-yourself” perfusable vasculature model that recapitulates in vivo geometries, such as aneurysms, stenoses, and bifurcations, and supports endothelial cell culture. These inexpensive, disposable devices can be created rapidly (<2 hours) with high precision and repeatability, using standard off-the-shelf laboratory supplies. Using these “endothelialized” systems, we demonstrate that spatial variation in vascular cell adhesion molecule (VCAM-1) expression correlates with the wall shear stress patterns of vascular geometries. We further observe that the presence of endothelial cells in stenoses reduces platelet adhesion but increases sickle cell disease (SCD) red blood cell (RBC) adhesion in bifurcations. Overall, our method enables researchers from all disciplines to study cellular interactions in physiologically relevant, yet simple-to-make, in vitro vasculature models. PMID:26202603

Computational Modeling of Pathophysiologic Responses to Exercise in Fontan Patients

PubMed Central

Kung, Ethan; Perry, James C.; Davis, Christopher; Migliavacca, Francesco; Pennati, Giancarlo; Giardini, Alessandro; Hsia, Tain-Yen; Marsden, Alison

2014-01-01

Reduced exercise capacity is nearly universal among Fontan patients. Although many factors have emerged as possible contributors, the degree to which each impacts the overall hemodynamics is largely unknown. Computational modeling provides a means to test hypotheses of causes of exercise intolerance via precisely controlled virtual experiments and measurements. We quantified the physiological impacts of commonly encountered, clinically relevant dysfunctions introduced to the exercising Fontan system via a previously developed lumped-parameter model of Fontan exercise. Elevated pulmonary arterial pressure was observed in all cases of dysfunction, correlated with lowered cardiac output, and often mediated by elevated atrial pressure. Pulmonary vascular resistance was not the most significant factor affecting exercise performance as measured by cardiac output. In the absence of other dysfunctions, atrioventricular valve insufficiency alone had significant physiological impact, especially under exercise demands. The impact of isolated dysfunctions can be linearly summed to approximate the combined impact of several dysfunctions occurring in the same system. A single dominant cause of exercise intolerance was not identified, though several hypothesized dysfunctions each led to variable decreases in performance. Computational predictions of performance improvement associated with various interventions should be weighed against procedural risks and potential complications, contributing to improvements in routine patient management protocol. PMID:25260878

Electromagnetic Fields, Oxidative Stress, and Neurodegeneration

PubMed Central

Consales, Claudia; Merla, Caterina; Marino, Carmela; Benassi, Barbara

2012-01-01

Electromagnetic fields (EMFs) originating both from both natural and manmade sources permeate our environment. As people are continuously exposed to EMFs in everyday life, it is a matter of great debate whether they can be harmful to human health. On the basis of two decades of epidemiological studies, an increased risk for childhood leukemia associated with Extremely Low Frequency fields has been consistently assessed, inducing the International Agency for Research on Cancer to insert them in the 2B section of carcinogens in 2001. EMFs interaction with biological systems may cause oxidative stress under certain circumstances. Since free radicals are essential for brain physiological processes and pathological degeneration, research focusing on the possible influence of the EMFs-driven oxidative stress is still in progress, especially in the light of recent studies suggesting that EMFs may contribute to the etiology of neurodegenerative disorders. This review synthesizes the emerging evidences about this topic, highlighting the wide data uncertainty that still characterizes the EMFs effect on oxidative stress modulation, as both pro-oxidant and neuroprotective effects have been documented. Care should be taken to avoid methodological limitations and to determine the patho-physiological relevance of any alteration found in EMFs-exposed biological system. PMID:22991514

Abnormal illness behaviour: physiological, psychological and social dimensions of coping with distress.

PubMed

Kirmayer, Laurence J; Looper, Karl J

2006-01-01

Pilowsky introduced the term 'abnormal illness behaviour' to characterize syndromes of excessive or inadequate response to symptoms, including hypochondriasis, somatization, and denial of illness. This review summarizes recent work from sociology, health psychology and psychiatry that contributes to an understanding of the processes that may underlie abnormal illness behaviour. Disturbances in the regulation of physiological systems may account for many 'unexplained' symptoms and sickness behaviour. Increased attention to bodily sensations, sensitivity to pain and catastrophizing play important roles in illness behaviour in medical illness. Developmental adversities and parental modelling of illness behaviour in childhood may increase bodily preoccupation and health care utilization. Apparent cross-national differences in illness behaviour may reflect differences in health care systems, but cultural models of illness and social stigma remain important determinants of illness denial and avoidance of mental health services. Research into illness behaviour is relevant to efforts to rethink the psychiatric nosology of somatoform disorders. The discrete somatoform disorders might well be replaced by a dimensional framework that identifies specific pathological processes in cognition, perception and social behaviour that contribute to bodily distress, impaired coping, inappropriate use of health services, chronicity and disability.

External incentives and internal states guide goal-directed behavior via the differential recruitment of the nucleus accumbens and the medial prefrontal cortex.

PubMed

Moscarello, J M; Ben-Shahar, O; Ettenberg, A

2010-10-13

Goal-directed behavior is governed by internal physiological states and external incentives present in the environment (e.g. hunger and food). While the role of the mesocorticolimbic dopamine (DA) system in behavior guided by environmental incentives has been well studied, the effect of relevant physiological states on the function of this system is less understood. The current study examined the role of the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAcc) in the kind of food-reinforced behaviors known to be sensitive to the internal state produced by food deprivation conditions. Operant lever-press reinforced on fixed ratio 1 (FR1) and progressive ratio (PR) schedules was tested after temporary inactivation of, or DA receptor blockade in, the prelimbic mPFC or NAcc core of rats with differing levels of food deprivation (0, 12 and 36-h). Food deprivation increased PR breakpoints, as well as the number of lever-presses emitted on the FR1 schedule. Both temporary inactivation and DA blockade of NAcc reduced breakpoints across deprivation conditions, while temporary inactivation and DA blockade of mPFC reduced breakpoints only in food-deprived rats. Neither manipulation of mPFC and NAcc had any effect on behavior reinforced on the FR1 schedule. Thus, mPFC and NAcc were differentially relevant to the behaviors tested-NAcc was recruited when the behavioral cost per reinforcer was rising or high regardless of food deprivation conditions, while mPFC was recruited when food-deprived animals behaved through periods of sparse reinforcement density in order to maximize available gain. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

A Laboratory Program for Bioinorganic Chemistry

ERIC Educational Resources Information Center

Ochiai, Ei-ichiro

1973-01-01

Outlines a laboratory course entitled Inorganic Chemistry for Biological Sciences'' which is designed primarily for juniors in biochemistry, physiology, and soil sciences. Inclusion of relevant environmental topics is indicated. (CC)

Understanding Lymphatic Valve Function via Computational Modeling

NASA Astrophysics Data System (ADS)

Wolf, Ki; Nepiyushchikh, Zhanna; Razavi, Mohammad; Dixon, Brandon; Alexeev, Alexander

2017-11-01

The lymphatic system is a crucial part to the circulatory system with many important functions, such as transport of interstitial fluid, fatty acid, and immune cells. Lymphatic vessels' contractile walls and valves allow lymph flow against adverse pressure gradients and prevent back flow. Yet, the effect of lymphatic valves' geometric and mechanical properties to pumping performance and lymphatic dysfunctions like lymphedema is not well understood. Our coupled fluid-solid computational model based on lattice Boltzmann model and lattice spring model investigates the dynamics and effectiveness of lymphatic valves in resistance minimization, backflow prevention, and viscoelastic response under different geometric and mechanical properties, suggesting the range of lymphatic valve parameters with effective pumping performance. Our model also provides more physiologically relevant relations of the valve response under varied conditions to a lumped parameter model of the lymphatic system giving an integrative insight into lymphatic system performance, including its failure due to diseases. NSF CMMI-1635133.

USSR Space Life Sciences Digest, issue 11

NASA Technical Reports Server (NTRS)

Hooke, Lydia Razran (Editor); Radtke, Mike (Editor); Radtke, Mike (Editor); Radtke, Mike (Editor); Radtke, Mike (Editor); Radtke, Mike (Editor)

1987-01-01

This is the eleventh issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 54 papers recently published in Russian language periodicals and bound collections and of four new Soviet monographs. Selected abstracts are illustrated. Additional features include the translation of a paper presented in Russian to the United Nations, a review of a book on space ecology, and report of a conference on evaluating human functional capacities and predicting health. Current Soviet Life Sciences titles available in English are cited. The materials included in this issue have been identified as relevant to 30 areas of aerospace medicine and space biology. These areas are: adaptation, aviation physiology, biological rhythms, biospherics, body fluids, botany, cardiovascular and respiratory systems, cosmonaut training, developmental biology, endocrinology, enzymology, equipment and instrumentation, gastrointestinal systems, group dynamics, genetics, hematology, human performance, immunology, life support systems, mathematical modeling, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, operational medicine, perception, personnel selection, psychology, and radiobiology.

USSR Space Life Sciences Digest, issue 19

NASA Technical Reports Server (NTRS)

Hooke, Lydia Razran (Editor); Donaldson, P. Lynn (Editor); Teeter, Ronald (Editor); Garshnek, Victoria (Editor); Rowe, Joseph (Editor)

1988-01-01

This is the 19th issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 47 papers published in Russian language periodicals or presented at conferences and of 5 new Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. Reports on two conferences, one on adaptation to high altitudes, and one on space and ecology are presented. A book review of a recent work on high altitude physiology is also included. The abstracts in this issue have been identified as relevant to 33 areas of space biology and medicine. These areas are: adaptation, biological rhythms, biospherics, body fluids, botany, cardiovascular and respiratory systems, cytology, developmental biology, endocrinology, enzymology, biology, group dynamics, habitability and environmental effects, hematology, human performance, immunology, life support systems, man-machine systems, mathematical modeling, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, operational medicine, perception, personnel selection, psychology, radiobiology, and space biology and medicine.

Three-Dimensional Cell Culture Systems and Their Applications in Drug Discovery and Cell-Based Biosensors

PubMed Central

Edmondson, Rasheena; Broglie, Jessica Jenkins; Adcock, Audrey F.

2014-01-01

Abstract Three-dimensional (3D) cell culture systems have gained increasing interest in drug discovery and tissue engineering due to their evident advantages in providing more physiologically relevant information and more predictive data for in vivo tests. In this review, we discuss the characteristics of 3D cell culture systems in comparison to the two-dimensional (2D) monolayer culture, focusing on cell growth conditions, cell proliferation, population, and gene and protein expression profiles. The innovations and development in 3D culture systems for drug discovery over the past 5 years are also reviewed in the article, emphasizing the cellular response to different classes of anticancer drugs, focusing particularly on similarities and differences between 3D and 2D models across the field. The progression and advancement in the application of 3D cell cultures in cell-based biosensors is another focal point of this review. PMID:24831787

Electrical Impedance Tomography of Electrolysis

PubMed Central

Meir, Arie; Rubinsky, Boris

2015-01-01

The primary goal of this study is to explore the hypothesis that changes in pH during electrolysis can be detected with Electrical Impedance Tomography (EIT). The study has relevance to real time control of minimally invasive surgery with electrolytic ablation. To investigate the hypothesis, we compare EIT reconstructed images to optical images acquired using pH-sensitive dyes embedded in a physiological saline agar gel phantom treated with electrolysis. We further demonstrate the biological relevance of our work using a bacterial E.Coli model, grown on the phantom. The results demonstrate the ability of EIT to image pH changes in a physiological saline phantom and show that these changes correlate with cell death in the E.coli model. The results are promising, and invite further experimental explorations. PMID:26039686

Waveform shape analysis: extraction of physiologically relevant information from Doppler recordings.

PubMed

Ramsay, M M; Broughton Pipkin, F; Rubin, P C; Skidmore, R

1994-05-01

1. Doppler recordings were made from the brachial artery of healthy female subjects during a series of manoeuvres which altered the pressure-flow characteristics of the vessel. 2. Changes were induced in the peripheral circulation of the forearm by the application of heat or ice-packs. A sphygmomanometer cuff was used to create graded occlusion of the vessel above and below the point of measurement. Recordings were also made whilst the subjects performed a standardized Valsalva manoeuvre. 3. The Doppler recordings were analysed both with the standard waveform indices (systolic/diastolic ratio, pulsatility index and resistance index) and by the method of Laplace transform analysis. 4. The waveform parameters obtained by Laplace transform analysis distinguished the different changes in flow conditions; they thus had direct physiological relevance, unlike the standard waveform indices.

[Signaling mechanisms involved in resolution of inflammation].

PubMed

Cervantes-Villagrana, Rodolfo Daniel; Cervantes-Villagrana, Alberto Rafael; Presno-Bernal, José Miguel

2014-01-01

Inflammation is a physiological process, which eliminates pathogens and induces repair of damaged tissue. This process is controlled by negative feedback mechanisms, but if the inflammation persists, it generates a deleterious autoimmune process or can to contribute with diseases such as obesity or cancer. The inflammation resolution involves mechanisms such as decrease of proliferation and maturation of immune cells, phagocytosis and apoptosis of immune cells, and decrease of proinflammatory mediators. Therefore, is relevant to study the physiological effects of specific receptors that participate in inflammation resolution and the design of specific agonists as conventional anti-inflammatory therapeutics, without dramatic collateral effects. In this review, we study some mechanisms associated with inflammation inhibition, particularly the transduction of receptors for ligands with anti-inflammatory effects and that are relevant for their potential therapeutic.

A data-driven modeling approach to stochastic computation for low-energy biomedical devices.

PubMed

Lee, Kyong Ho; Jang, Kuk Jin; Shoeb, Ali; Verma, Naveen

2011-01-01

Low-power devices that can detect clinically relevant correlations in physiologically-complex patient signals can enable systems capable of closed-loop response (e.g., controlled actuation of therapeutic stimulators, continuous recording of disease states, etc.). In ultra-low-power platforms, however, hardware error sources are becoming increasingly limiting. In this paper, we present how data-driven methods, which allow us to accurately model physiological signals, also allow us to effectively model and overcome prominent hardware error sources with nearly no additional overhead. Two applications, EEG-based seizure detection and ECG-based arrhythmia-beat classification, are synthesized to a logic-gate implementation, and two prominent error sources are introduced: (1) SRAM bit-cell errors and (2) logic-gate switching errors ('stuck-at' faults). Using patient data from the CHB-MIT and MIT-BIH databases, performance similar to error-free hardware is achieved even for very high fault rates (up to 0.5 for SRAMs and 7 × 10(-2) for logic) that cause computational bit error rates as high as 50%.

The role of heart rate variability in sports physiology

PubMed Central

DONG, JIN-GUO

2016-01-01

Heart rate variability (HRV) is a relevant marker reflecting cardiac modulation by sympathetic and vagal components of the autonomic nervous system (ANS). Although the clinical application of HRV is mainly associated with the prediction of sudden cardiac death and assessing cardiovascular and metabolic illness progression, recent observations have suggested its applicability to physical exercise training. HRV is becoming one of the most useful tools for tracking the time course of training adaptation/maladaptation of athletes and in setting the optimal training loads leading to improved performances. However, little is known regarding the role of HRV and the internal effects of physical exercise on an athlete, which may be useful in designing fitness programs ensuring sufficient training load that may correspond with the specific ability of the athlete. In this review, we offer a comprehensive assessment of investigations concerning the interrelation between HRV and ANS, and examine how the application of HRV to physical exercise may play a role in sports physiology. PMID:27168768

Hyperhomocysteinemia and neurologic disorders: a review.

PubMed

Ansari, Ramin; Mahta, Ali; Mallack, Eric; Luo, Jin Jun

2014-10-01

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders.

Hyperhomocysteinemia and Neurologic Disorders: a Review

PubMed Central

Ansari, Ramin; Mallack, Eric; Luo, Jin Jun

2014-01-01

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. It has a physiologic role in DNA metabolism via methylation, a process governed by the presentation of folate, and vitamins B6 and B12. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy (eHcy) can be caused by deficiency of either vitamin B12 or folate, or a combination thereof. Certain genetic factors also cause eHcy, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. eHcy has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that Hcy, and especially eHcy, exerts direct toxic effects on both the vascular and nervous systems. This article provides a review of the current literature on the possible roles of eHcy relevant to various neurologic disorders. PMID:25324876

The role of heart rate variability in sports physiology.

PubMed

Dong, Jin-Guo

2016-05-01

Heart rate variability (HRV) is a relevant marker reflecting cardiac modulation by sympathetic and vagal components of the autonomic nervous system (ANS). Although the clinical application of HRV is mainly associated with the prediction of sudden cardiac death and assessing cardiovascular and metabolic illness progression, recent observations have suggested its applicability to physical exercise training. HRV is becoming one of the most useful tools for tracking the time course of training adaptation/maladaptation of athletes and in setting the optimal training loads leading to improved performances. However, little is known regarding the role of HRV and the internal effects of physical exercise on an athlete, which may be useful in designing fitness programs ensuring sufficient training load that may correspond with the specific ability of the athlete. In this review, we offer a comprehensive assessment of investigations concerning the interrelation between HRV and ANS, and examine how the application of HRV to physical exercise may play a role in sports physiology.

Advances Towards The Discovery of GPR55 Ligands.

PubMed

Morales, Paula; Jagerovic, Nadine

2016-01-01

The G-protein-coupled receptor 55 (GPR55) was identified in 1999. It was proposed as a novel member of the endocannabinoid system due to the fact that some endogenous, plant-derived and synthetic cannabinoid ligands act on GPR55. However, the complexity of the cellular downstream signaling pathways related to GPR55 activation delayed the discovery of selective GPR55 ligands. It was only a few years ago that the high throughput screening of libraries of pharmaceutical companies and governmental organizations allowed to identify selective GPR55 agonists and antagonists. Since then, several GPR55 modulator scaffolds have been reported. The relevance of GPR55 has been explored in diverse physiological and pathological processes revealing its role in inflammation, neuropathic pain, bone physiology, diabetes and cancer. Considering GPR55 as a new promising therapeutic target, there is a clear need for new selective and potent GPR55 modulators. This review will address a current structural update of GPR55 ligands.

Effects of Caffeine on Olfactory Learning in Crickets.

PubMed

Sugimachi, Seigo; Matsumoto, Yukihisa; Mizunami, Makoto; Okada, Jiro

2016-10-01

Caffeine is a plant-derived alkaloid that is generally known as a central nervous system (CNS) stimulant. In order to examine the effects of caffeine on higher CNS functions in insects, we used an appetitive olfactory learning paradigm for the cricket Gryllus bimaculatus. Crickets can form significant long-term memories (LTMs) after repetitive training sessions, during which they associate a conditioned stimulus (CS: odor) with an unconditioned stimulus (US: reward). Administration of hemolymphal injections of caffeine established LTM after only single-trial conditioning over a wide range of caffeine dosages (1.6 µµg/kg to 39 mg/kg). We investigated the physiological mechanisms underlying this enhancement of olfactory learning performance pharmacologically, focusing on three major physiological roles of caffeine: 1) inhibition of phosphodiesterase (PDE), 2) agonism of ryanodine receptors, and 3) antagonism of adenosine receptors. Application of drugs relevant to these actions resulted in significant effects on LTM formation. These results suggest that externally applied caffeine enhances LTM formation in insect olfactory learning via multiple cellular mechanisms.

Mechanical stress activates NMDA receptors in the absence of agonists.

PubMed

Maneshi, Mohammad Mehdi; Maki, Bruce; Gnanasambandam, Radhakrishnan; Belin, Sophie; Popescu, Gabriela K; Sachs, Frederick; Hua, Susan Z

2017-01-03

While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca 2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca 2+ influx. Extracellular Mg 2+ at 2 mM did not significantly affect the shear induced Ca 2+ influx, but at 10 mM it produced significant inhibition. Patch clamp experiments showed mechanical activation of NMDAR and inhibition by MK-801. The mechanical sensitivity of NMDARs may play a role in the normal physiology of fluid flow in the glymphatic system and it has obvious relevance to TBI.

Does selection for short sleep duration explain human vulnerability to Alzheimer’s disease?

PubMed Central

Nesse, Randolph M; Finch, Caleb E; Nunn, Charles L

2017-01-01

Abstract Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer ’s disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin—a peptide hormone that increases markedly during sleep—is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD. Sleep deprivation increases plaque formation and AD, which itself disrupts sleep, potentially creating a positive feedback cycle. These and other physiological benefits of sleep may be compromised by short sleep durations. Our hypothesis highlights possible long-term side effects of medications that reduce sleep, and may lead to potential new strategies for preventing and treating AD. PMID:28096295

Mechanical stress activates NMDA receptors in the absence of agonists

PubMed Central

Maneshi, Mohammad Mehdi; Maki, Bruce; Gnanasambandam, Radhakrishnan; Belin, Sophie; Popescu, Gabriela K.; Sachs, Frederick; Hua, Susan Z.

2017-01-01

While studying the physiological response of primary rat astrocytes to fluid shear stress in a model of traumatic brain injury (TBI), we found that shear stress induced Ca2+ entry. The influx was inhibited by MK-801, a specific pore blocker of N-Methyl-D-aspartic acid receptor (NMDAR) channels, and this occurred in the absence of agonists. Other NMDA open channel blockers ketamine and memantine showed a similar effect. The competitive glutamate antagonists AP5 and GluN2B-selective inhibitor ifenprodil reduced NMDA-activated currents, but had no effect on the mechanically induced Ca2+ influx. Extracellular Mg2+ at 2 mM did not significantly affect the shear induced Ca2+ influx, but at 10 mM it produced significant inhibition. Patch clamp experiments showed mechanical activation of NMDAR and inhibition by MK-801. The mechanical sensitivity of NMDARs may play a role in the normal physiology of fluid flow in the glymphatic system and it has obvious relevance to TBI. PMID:28045032

The Arabidopsis thaliana aquaporin AtPIP1;2 is a physiologically relevant CO₂ transport facilitator.

PubMed

Heckwolf, Marlies; Pater, Dianne; Hanson, David T; Kaldenhoff, Ralf

2011-09-01

Cellular exchange of carbon dioxide (CO₂) is of extraordinary importance for life. Despite this significance, its molecular mechanisms are still unclear and a matter of controversy. In contrast to other living organisms, plants are physiologically limited by the availability of CO₂. In most plants, net photosynthesis is directly dependent on CO₂ diffusion from the atmosphere to the chloroplast. Thus, it is important to analyze CO₂ transport with regards to its effect on photosynthesis. A mutation of the Arabidopsis thaliana AtPIP1;2 gene, which was characterized as a non-water transporting but CO₂ transport-facilitating aquaporin in heterologous expression systems, correlated with a reduction in photosynthesis under a wide range of atmospheric CO₂ concentrations. Here, we could demonstrate that the effect was caused by reduced CO₂ conductivity in leaf tissue. It is concluded that the AtPIP1;2 gene product limits CO₂ diffusion and photosynthesis in leaves. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Drug-Induced Alterations of Endocannabinoid-Mediated Plasticity in Brain Reward Regions.

PubMed

Zlebnik, Natalie E; Cheer, Joseph F

2016-10-05

The endocannabinoid (eCB) system has emerged as one of the most important mediators of physiological and pathological reward-related synaptic plasticity. eCBs are retrograde messengers that provide feedback inhibition, resulting in the suppression of neurotransmitter release at both excitatory and inhibitory synapses, and they serve a critical role in the spatiotemporal regulation of both short- and long-term synaptic plasticity that supports adaptive learning of reward-motivated behaviors. However, mechanisms of eCB-mediated synaptic plasticity in reward areas of the brain are impaired following exposure to drugs of abuse. Because of this, it is theorized that maladaptive eCB signaling may contribute to the development and maintenance of addiction-related behavior. Here we review various forms of eCB-mediated synaptic plasticity present in regions of the brain involved in reward and reinforcement and explore the potential physiological relevance of maladaptive eCB signaling to addiction vulnerability. Copyright © 2016 the authors 0270-6474/16/3610230-09$15.00/0.

Memory-updating abrogates extinction of learned immunosuppression.

PubMed

Hadamitzky, Martin; Bösche, Katharina; Wirth, Timo; Buck, Benjamin; Beetz, Oliver; Christians, Uwe; Schniedewind, Björn; Lückemann, Laura; Güntürkün, Onur; Engler, Harald; Schedlowski, Manfred

2016-02-01

When memories are recalled, they enter a transient labile phase in which they can be impaired or enhanced followed by a new stabilization process termed reconsolidation. It is unknown, however, whether reconsolidation is restricted to neurocognitive processes such as fear memories or can be extended to peripheral physiological functions as well. Here, we show in a paradigm of behaviorally conditioned taste aversion in rats memory-updating in learned immunosuppression. The administration of sub-therapeutic doses of the immunosuppressant cyclosporin A together with the conditioned stimulus (CS/saccharin) during retrieval blocked extinction of conditioned taste aversion and learned suppression of T cell cytokine (interleukin-2; interferon-γ) production. This conditioned immunosuppression is of clinical relevance since it significantly prolonged the survival time of heterotopically transplanted heart allografts in rats. Collectively, these findings demonstrate that memories can be updated on both neural and behavioral levels as well as on the level of peripheral physiological systems such as immune functioning. Copyright © 2015 Elsevier Inc. All rights reserved.

Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward.

PubMed

Volkow, Nora D; Hampson, Aidan J; Baler, Ruben D

2017-01-06

Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and other adverse consequences. The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis. Here we review our current understanding of the ECS and its complex physiological roles. We discuss the implications of this understanding vis-á-vis the ECS's modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions.

PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes

PubMed Central

Ferguson, Ross; Subramanian, Vasanta

2016-01-01

Neuroblastoma cell lines such as SH-SY5Y have been used for modelling neurodegenerative diseases and for studying basic mechanisms in neuroscience. Since neuroblastoma cells proliferate and generally do not express markers of mature or functional neurons, we exploited a co-culture system with the stromal cell line PA6 to better induce differentiation to a more physiologically relevant status. We found that co-culture of the neuroblastoma cell lines in the presence of neural inducers such retinoic acid was able to generate a high proportion of quiescent neurons with very long neurites expressing differentiation markers. The co-culture system additionally cuts short the time taken to produce a more mature phenotype. We also show the application of this system to study proteins implicated in motor neuron disease. PMID:27391595

PA6 Stromal Cell Co-Culture Enhances SH-SY5Y and VSC4.1 Neuroblastoma Differentiation to Mature Phenotypes.

PubMed

Ferguson, Ross; Subramanian, Vasanta

2016-01-01

Neuroblastoma cell lines such as SH-SY5Y have been used for modelling neurodegenerative diseases and for studying basic mechanisms in neuroscience. Since neuroblastoma cells proliferate and generally do not express markers of mature or functional neurons, we exploited a co-culture system with the stromal cell line PA6 to better induce differentiation to a more physiologically relevant status. We found that co-culture of the neuroblastoma cell lines in the presence of neural inducers such retinoic acid was able to generate a high proportion of quiescent neurons with very long neurites expressing differentiation markers. The co-culture system additionally cuts short the time taken to produce a more mature phenotype. We also show the application of this system to study proteins implicated in motor neuron disease.

Fully automated laser ray tracing system to measure changes in the crystalline lens GRIN profile.

PubMed

Qiu, Chen; Maceo Heilman, Bianca; Kaipio, Jari; Donaldson, Paul; Vaghefi, Ehsan

2017-11-01

Measuring the lens gradient refractive index (GRIN) accurately and reliably has proven an extremely challenging technical problem. A fully automated laser ray tracing (LRT) system was built to address this issue. The LRT system captures images of multiple laser projections before and after traversing through an ex vivo lens. These LRT images, combined with accurate measurements of the lens geometry, are used to calculate the lens GRIN profile. Mathematically, this is an ill-conditioned problem; hence, it is essential to apply biologically relevant constraints to produce a feasible solution. The lens GRIN measurements were compared with previously published data. Our GRIN retrieval algorithm produces fast and accurate measurements of the lens GRIN profile. Experiments to study the optics of physiologically perturbed lenses are the future direction of this research.

Fully automated laser ray tracing system to measure changes in the crystalline lens GRIN profile

PubMed Central

Qiu, Chen; Maceo Heilman, Bianca; Kaipio, Jari; Donaldson, Paul; Vaghefi, Ehsan

2017-01-01

Measuring the lens gradient refractive index (GRIN) accurately and reliably has proven an extremely challenging technical problem. A fully automated laser ray tracing (LRT) system was built to address this issue. The LRT system captures images of multiple laser projections before and after traversing through an ex vivo lens. These LRT images, combined with accurate measurements of the lens geometry, are used to calculate the lens GRIN profile. Mathematically, this is an ill-conditioned problem; hence, it is essential to apply biologically relevant constraints to produce a feasible solution. The lens GRIN measurements were compared with previously published data. Our GRIN retrieval algorithm produces fast and accurate measurements of the lens GRIN profile. Experiments to study the optics of physiologically perturbed lenses are the future direction of this research. PMID:29188093

Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System.

PubMed

Forrester, Steven J; Kawai, Tatsuo; O'Brien, Shannon; Thomas, Walter; Harris, Raymond C; Eguchi, Satoru

2016-01-01

Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.

USSR Space Life Sciences Digest, issue 3

NASA Technical Reports Server (NTRS)

Hooke, L. R. (Editor); Radtke, M. (Editor); Garshnek, V. (Editor); Rowe, J. E. (Editor); Teeter, R. (Editor)

1985-01-01

This is the third issue of NASA's USSR Space Life Sciences Digest. Abstracts are included for 46 Soviet periodical articles in 20 areas of aerospace medicine and space biology and published in Russian during the second third of 1985. Selected articles are illustrated with figures and tables from the original. In addition, translated introductions and tables of contents for seven Russian books on six topics related to NASA's life science concerns are presented. Areas covered are adaptation, biospherics, body fluids, botany, cardiovascular and respiratory systems, endocrinology, exobiology, gravitational biology, habitability and environmental effects, health and medical treatment, immunology, life support systems, metabolism, microbiology, musculoskeletal system; neurophysiology, nutrition, perception, personnel selection, psychology, radiobiology, and space physiology. Two book reviews translated from the Russian are included and lists of additional relevant titles available in English with pertinent ordering information are given.

The TCAR Report: Translational Cell and Animal Research Space (1965-2011) Sponsored by NASA Ames Research Center

NASA Technical Reports Server (NTRS)

Ronca, A. E.; Mains, Richard; Alwood, J. S.; French, A. J.; Smith, J. D.; Miller, Virginia; Tash, Joseph; Jenkins, Marjorie

2015-01-01

Five decades ago, NASA Ames Research Center (ARC) began a vigorous program of space biology research utilizing animal cells, tissues and whole organisms. Since its inception, this program has yielded exciting new insights into how spaceflight influences fundamental processes of living systems. These are findings with important translational implications for human health in space and on Earth. The TCAR Report is a compilation of 394 flight experiments conducted across the period spanning 1965 - 2011 with individual chapters devoted to: (1) Bone Physiology, (2) Cardiovascular/Cardiopulmonary Physiology, (3) Developmental Biology, (4) Immunology, (5) Microbial Growth and Virulence, (6) Muscle Physiology, (7) Neurophysiology and (8) Regulatory Physiology. Specialists in those disciplines reviewed the research and each prepared an overview including the translational relevance of the findings for human health in space and on Earth. The Report will be made available in early 2015 through standard NASA publication resources and on the NASA Life Sciences Data Archive (http://lsda.jsc.nasa.gov/lsda_home1.aspx). The LSDA can be mined for detailed information, including Experiment, Mission, Available Biospecimens, Document, Hardware, Dataset, Personnel, and includes a searchable Photo Gallery. Space biology translational topic highlights include: Inflight centrifugation protection of bone strength losses; Assessment of evidence related to visual impairment in astronauts; Mammalian development including vestibular system plasticity and vestibular-visual integration; Verification of limb unloading ground-based studies as a model for spaceflight unloading; Immune system impairment and increased microbiological virulence aligned with immune dysfunction; and Rapid bone and muscle tissue and functional losses associated with unloading. In addition to astronauts, these results may help humans on Earth, by providing insight into the definition of fundamental mechanisms and potential treatments for debilitating changes that result from human aging and disease. The TCAR effort has resulted in significant new insights. Modern tools now widely available for "Omics" research with model organisms and humans provide new opportunities for translational research. Omics research at various levels is greatly complemented by studies at the tissue and organismal levels. Key discoveries can occur at either the basic research or the health surveillance level such as vision problems observed in astronauts stimulating studies of eye tissues in rodents that identified relevant changes. The Ames Biospecimen Sharing Program (BSP), serving the NASA Space Biology and HRP programs, was created to maximize utilization and scientific return from unique animal specimens derived from rare, complex and costly NASA spaceflight and ground-based analog experiments. The BSP is a valuable tool for advancing translational science at NASA. Dynamic methods for tracking translational linkages across NASA space life sciences and medicine are strongly encouraged for translational science.

The Csr/Rsm system of Yersinia and related pathogens: a post-transcriptional strategy for managing virulence.

PubMed

Heroven, Ann Kathrin; Böhme, Katja; Dersch, Petra

2012-04-01

This review emphasizes the function and regulation of the Csr regulatory system in the human enteropathogen Yersinia pseudotuberculosis and compares its features with the homologous Csr/Rsm systems of related pathogens. The Csr/Rsm systems of eubacteria form a complex regulatory network in which redundant non-translated Csr/Rsm-RNAs bind the RNA-binding protein CsrA/RsmA, thereby preventing its interaction with mRNA targets. The Csr system is controlled by the BarA/UvrY-type of two-component sensor-regulator systems. Apart from that, common or pathogen-specific regulators control the abundance of the Csr components. The coordinate control of virulence factors and infection-linked physiological traits by the Csr/Rsm systems helps the pathogens to adapt individually to rapidly changing conditions to which they are exposed during the different stages of an infection. As Csr/Rsm function is relevant for full virulence, it represents a target suitable for antimicrobial drug development.

Theoretical analysis of insulin-dependent glucose uptake heterogeneity in 3D bioreactor cell culture.

PubMed

Magrofuoco, Enrico; Elvassore, Nicola; Doyle, Francis J

2012-01-01

Three-dimensional (3D) cell cultures in bioreactors are becoming relevant as models for biological and physiological in vitro studies. In such systems, mathematical models can assist the experiment design that links the macroscopic properties to single-cell responses. We investigated the relationship between biochemical stimuli and cell response within a 3D cell culture in scaffold with heterogeneous porosity. Specifically, we studied the effect of insulin on the local glucose metabolism as a function of 3D pore size distribution. The multiscale mathematical model combines the mass transport within a 3D scaffold and a signaling pathways model. It considers the scaffold heterogeneity, and it describes spatiotemporal concentration of metabolites, biochemical stimuli, and cell density. The signaling model was integrated into this model, linking the local insulin concentration at cell membrane to the glucose uptake rate through glucose transporter type 4 (GLUT4) translocation from the cytosol to the cell membrane. The integrated model determines the cell response heterogeneities in a single channel, hence the biological response distribution in a 3D system. It also provides macroscopic outcomes to evaluate the feasibility of an experimental measurement of the system response. From our analysis, it became apparent that the flow rate is the most important operative variable, and that an optimum value ensures a fast and detectable cell response. This model on insulin-dependent glucose consumption rate offers insight into the cell metabolism physiology, which is a fundamental requirement for the study metabolic disorder such as Type 2 diabetes mellitus, in which the physiological insulin-dependent glucose metabolism is impaired. Copyright © 2012 American Institute of Chemical Engineers (AIChE).

Vascularization of Air Sinuses and Fat Bodies in the Head of the Bottlenose Dolphin (Tursiops truncatus): Morphological Implications on Physiology

PubMed Central

Costidis, Alex; Rommel, Sentiel A.

2012-01-01

Cetaceans have long been considered capable of limiting diving-induced nitrogen absorption and subsequent decompression sickness through a series of behavioral, anatomical, and physiological adaptations. Recent studies however suggest that in some situations these adaptive mechanisms might be overcome, resulting in lethal and sublethal injuries. Perhaps most relevant to this discussion is the finding of intravascular gas and fat emboli in mass-stranded beaked whales. Although the source of the gas emboli has as yet to been ascertained, preliminary findings suggest nitrogen is the primary component. Since nitrogen gas embolus formation in divers is linked to nitrogen saturation, it seems premature to dismiss similar pathogenic mechanisms in breath-hold diving cetaceans. Due to the various anatomical adaptations in cetacean lungs, the pulmonary system is thought of as an unlikely site of significant nitrogen absorption. The accessory sinus system on the ventral head of odontocete cetaceans contains a sizeable volume of air that is exposed to the changing hydrostatic pressures during a dive, and is intimately associated with vasculature potentially capable of absorbing nitrogen through its walls. The source of the fat emboli has also remained elusive. Most mammalian fat deposits are considered poorly vascularized and therefore unlikely sites of intravascular introduction of lipid, although cetacean blubber may not be as poorly vascularized as previously thought. We present new data on the vasculature of air sinuses and acoustic fat bodies in the head of bottlenose dolphins and compare it to published accounts. We show that the mandibular fat bodies and accessory sinus system are associated with extensive venous plexuses and suggest potential physiological and pathological implications. PMID:22969724

Does a 20-week aerobic exercise training programme increase our capabilities to buffer real-life stressors? A randomized, controlled trial using ambulatory assessment.

PubMed

von Haaren, Birte; Ottenbacher, Joerg; Muenz, Julia; Neumann, Rainer; Boes, Klaus; Ebner-Priemer, Ulrich

2016-02-01

The cross-stressor adaptation hypothesis suggests that regular exercise leads to adaptations in the stress response systems that induce decreased physiological responses to psychological stressors. Even though an exercise intervention to buffer the detrimental effects of psychological stressors on health might be of utmost importance, empirical evidence is mixed. This may be explained by the use of cross-sectional designs and non-personally relevant stressors. Using a randomized controlled trial, we hypothesized that a 20-week aerobic exercise training does reduce physiological stress responses to psychological real-life stressors in sedentary students. Sixty-one students were randomized to either a control group or an exercise training group. The academic examination period (end of the semester) served as a real-life stressor. We used ambulatory assessment methods to assess physiological stress reactivity of the autonomic nervous system (heart rate variability: LF/HF, RMSSD), physical activity and perceived stress during 2 days of everyday life and multilevel models for data analyses. Aerobic capacity (VO2max) was assessed pre- and post-intervention via cardiopulmonary exercise testing to analyze the effectiveness of the intervention. During real-life stressors, the exercise training group showed significantly reduced LF/HF (β = -0.15, t = -2.59, p = .01) and increased RMSSD (β = 0.15, t = 2.34, p = .02) compared to the control group. Using a randomized controlled trial and a real-life stressor, we could show that exercise appears to be a useful preventive strategy to buffer the effects of stress on the autonomic nervous system, which might result into detrimental health outcomes.

A murine model of a novel surgical architecture for proprioceptive muscle feedback and its potential application to control of advanced limb prostheses

NASA Astrophysics Data System (ADS)

Clites, Tyler R.; Carty, Matthew J.; Srinivasan, Shriya; Zorzos, Anthony N.; Herr, Hugh M.

2017-06-01

Objective. Proprioceptive mechanisms play a critical role in both reflexive and volitional lower extremity control. Significant strides have been made in the development of bionic limbs that are capable of bi-directional communication with the peripheral nervous system, but none of these systems have been capable of providing physiologically-relevant muscle-based proprioceptive feedback through natural neural pathways. In this study, we present the agonist-antagonist myoneural interface (AMI), a surgical approach with the capacity to provide graded kinesthetic feedback from a prosthesis through mechanical activation of native mechanoreceptors within residual agonist-antagonist muscle pairs. Approach. (1) Sonomicrometery and electroneurography measurement systems were validated using a servo-based muscle tensioning system. (2) A heuristic controller was implemented to modulate functional electrical stimulation of an agonist muscle, using sonomicrometric measurements of stretch from a mechanically-coupled antagonist muscle as feedback. (3) One AMI was surgically constructed in the hindlimb of each rat. (4) The gastrocnemius-soleus complex of the rat was cycled through a series of ramp-and-hold stretches in two different muscle architectures: native (physiologically-intact) and AMI (modified). Integrated electroneurography from the tibial nerve was compared across the two architectures. Main results. Correlation between stretch and afferent signal demonstrated that the AMI is capable of provoking graded afferent signals in response to ramp-and-hold stretches, in a manner similar to the native muscle architecture. The response magnitude in the AMI was reduced when compared to the native architecture, likely due to lower stretch amplitudes. The closed-loop control system showed robustness at high stretch magnitudes, with some oscillation at low stretch magnitudes. Significance. These results indicate that the AMI has the potential to communicate meaningful kinesthetic feedback from a prosthetic limb by replicating the agonist-antagonist relationships that are fundamental to physiological proprioception.

Use of CRISPR/Cas9-engineered INS-1 pancreatic β cells to define the pharmacology of dual GIPR/GLP-1R agonists.

PubMed

Naylor, Jacqueline; Suckow, Arthur T; Seth, Asha; Baker, David J; Sermadiras, Isabelle; Ravn, Peter; Howes, Rob; Li, Jianliang; Snaith, Mike R; Coghlan, Matthew P; Hornigold, David C

2016-09-15

Dual-agonist molecules combining glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) activity represent an exciting therapeutic strategy for diabetes treatment. Although challenging due to shared downstream signalling pathways, determining the relative activity of dual agonists at each receptor is essential when developing potential novel therapeutics. The challenge is exacerbated in physiologically relevant cell systems expressing both receptors. To this end, either GIP receptors (GIPR) or GLP-1 receptors (GLP-1R) were ablated via RNA-guided clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 endonucleases in the INS-1 pancreatic β-cell line. Multiple clonal cell lines harbouring gene disruptions for each receptor were isolated and assayed for receptor activity to identify functional knockouts (KOs). cAMP production in response to GIPR or GLP-1R activation was abolished and GIP- or GLP-1-induced potentiation of glucose-stimulated insulin secretion (GSIS) was attenuated in the cognate KO cell lines. The contributions of individual receptors derived from cAMP and GSIS assays were confirmed in vivo using GLP-1R KO mice in combination with a monoclonal antibody antagonist of GIPR. We have successfully applied CRISPR/Cas9-engineered cell lines to determining selectivity and relative potency contributions of dual-agonist molecules targeting receptors with overlapping native expression profiles and downstream signalling pathways. Specifically, we have characterised molecules as biased towards GIPR or GLP-1R, or with relatively balanced potency in a physiologically relevant β-cell system. This demonstrates the broad utility of CRISPR/Cas9 when applied to native expression systems for the development of drugs that target multiple receptors, particularly where the balance of receptor activity is critical. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Demand for interdisciplinary laboratories for physiology research by undergraduate students in biosciences and biomedical engineering.

PubMed

Clase, Kari L; Hein, Patrick W; Pelaez, Nancy J

2008-12-01

Physiology as a discipline is uniquely positioned to engage undergraduate students in interdisciplinary research in response to the 2006-2011 National Science Foundation Strategic Plan call for innovative transformational research, which emphasizes multidisciplinary projects. To prepare undergraduates for careers that cross disciplinary boundaries, students need to practice interdisciplinary communication in academic programs that connect students in diverse disciplines. This report surveys policy documents relevant to this emphasis on interdisciplinary training and suggests a changing role for physiology courses in bioscience and engineering programs. A role for a physiology course is increasingly recommended for engineering programs, but the study of physiology from an engineering perspective might differ from the study of physiology as a basic science. Indeed, physiology laboratory courses provide an arena where biomedical engineering and bioscience students can apply knowledge from both fields while cooperating in multidisciplinary teams under specified technical constraints. Because different problem-solving approaches are used by students of engineering and bioscience, instructional innovations are needed to break down stereotypes between the disciplines and create an educational environment where interdisciplinary teamwork is used to bridge differences.

I.M. Sechenov (1829 - 1905) and the scientific self-understanding for medical sciences.

PubMed

Kofler, Walter

2007-01-01

There is no discussion about the historic relevance of I. Sechenov for physiology and neurosciences as the "father of Russian modern physiology". But he is relevant for modern natural science too because of his basic epistemological and ontological work. He did not accept the up to now basic paradigm of "Ignorabimus" which can be seen as the reason to exclude even the generalizable aspects of individuality, creativity and spontaneity from natural science. He developed techniques for empirical based science to deal with materialistic and idealistic aspects of the comprehensive person the "ignoramus" according to the actual stay of knowledge and the acceptable ontologies. He demonstrated that ontologies ("paradigms") can be used as tools according to the given problem which should be solved. So Sechenov can be seen as a precursor of the so efficient philosophical positions of Einstein and Th. Kuhn. The stay of the art in physiology and neurosciences changed since the time of Sechenov dramatically. Therefore the philosophical positions of the 19th century should be discussed. Maybe this is indispensable for the needed linkage between materialistic and idealistic aspects of a person. For this the proposals of Sechenov are helpful up to now but nearly unknown. There is no discussion about the historic relevance of I. Sechenov as the "father of Russian physiology." But he is relevant for modern natural science too because of his epistemological and ontological work. He did not accept the up to now basic paradigm of "Ignorabimus" that can be seen as the reason to exclude even the generalizable aspects of individuality, creativity, and spontaneity from natural science. He demonstrated that ontologies ("paradigms") and epistemology can be used as tools according to the given problem. So Sechenov can be seen as a precursor of the so efficient philosophical positions of Einstein and Th. Kuhn. The state of the art changed dramatically. Therefore, the philosophical positions of the nineteenth century should be questioned. Maybe this is indispensable for the needed link between materialistic and idealistic aspects of a person as a whole. In this respect the proposals of Sechenov are helpful for medical science in the twenty-first century too but nearly unknown.

Gastrointestinal Physiology and Function.

PubMed

Greenwood-Van Meerveld, Beverley; Johnson, Anthony C; Grundy, David

2017-01-01

The gastrointestinal (GI) system is responsible for the digestion and absorption of ingested food and liquids. Due to the complexity of the GI tract and the substantial volume of material that could be covered under the scope of GI physiology, this chapter briefly reviews the overall function of the GI tract, and discusses the major factors affecting GI physiology and function, including the intestinal microbiota, chronic stress, inflammation, and aging with a focus on the neural regulation of the GI tract and an emphasis on basic brain-gut interactions that serve to modulate the GI tract. GI diseases refer to diseases of the esophagus, stomach, small intestine, colon, and rectum. The major symptoms of common GI disorders include recurrent abdominal pain and bloating, heartburn, indigestion/dyspepsia, nausea and vomiting, diarrhea, and constipation. GI disorders rank among the most prevalent disorders, with the most common including esophageal and swallowing disorders, gastric and peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Many GI disorders are difficult to diagnose and their symptoms are not effectively managed. Thus, basic research is required to drive the development of novel therapeutics which are urgently needed. One approach is to enhance our understanding of gut physiology and pathophysiology especially as it relates to gut-brain communications since they have clinical relevance to a number of GI complaints and represent a therapeutic target for the treatment of conditions including inflammatory diseases of the GI tract such as IBD and functional gut disorders such as IBS.

Low-dose ionizing radiation limitations to seed germination: Results from a model linking physiological characteristics and developmental-dynamics simulation strategy.

PubMed

Liu, Hui; Hu, Dawei; Dong, Chen; Fu, Yuming; Liu, Guanghui; Qin, Youcai; Sun, Yi; Liu, Dianlei; Li, Lei; Liu, Hong

2017-08-01

There is much uncertainty about the risks of seed germination after repeated or protracted environmental low-dose ionizing radiation exposure. The purpose of this study is to explore the influence mechanism of low-dose ionizing radiation on wheat seed germination using a model linking physiological characteristics and developmental-dynamics simulation. A low-dose ionizing radiation environment simulator was built to investigate wheat (Triticum aestivum L.) seeds germination process and then a kinetic model expressing the relationship between wheat seed germination dynamics and low-dose ionizing radiation intensity variations was developed by experimental data, plant physiology, relevant hypotheses and system dynamics, and sufficiently validated and accredited by computer simulation. Germination percentages were showing no differences in response to different dose rates. However, root and shoot lengths were reduced significantly. Plasma governing equations were set up and the finite element analysis demonstrated H 2 O, CO 2 , O 2 as well as the seed physiological responses to the low-dose ionizing radiation. The kinetic model was highly valid, and simultaneously the related influence mechanism of low-dose ionizing radiation on wheat seed germination proposed in the modeling process was also adequately verified. Collectively these data demonstrate that low-dose ionizing radiation has an important effect on absorbing water, consuming O 2 and releasing CO 2 , which means the risk for embryo and endosperm development was higher. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thyrotropin-Releasing Hormone (TRH) Promotes Wound Re-Epithelialisation in Frog and Human Skin

PubMed Central

Zhang, Guo-You; Emelianov, Vladimir; Paredes, Roberto; Debus, Sebastian; Augustin, Matthias; Funk, Wolfgang; Amaya, Enrique; Kloepper, Jennifer E.; Hardman, Matthew J.; Paus, Ralf

2013-01-01

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters. PMID:24023889

Murine epithelial cells: isolation and culture.

PubMed

Davidson, Donald J; Gray, Michael A; Kilanowski, Fiona M; Tarran, Robert; Randell, Scott H; Sheppard, David N; Argent, Barry E; Dorin, Julia R

2004-08-01

We describe an air-liquid interface primary culture method for murine tracheal epithelial cells on semi-permeable membranes, forming polarized epithelia with a high transepithelial resistance, differentiation to ciliated and secretory cells, and physiologically appropriate expression of key genes and ion channels. We also describe the isolation of primary murine nasal epithelial cells for patch-clamp analysis, generating polarised cells with physiologically appropriate distribution and ion channel expression. These methods enable more physiologically relevant analysis of murine airway epithelial cells in vitro and ex vivo, better utilisation of transgenic mouse models of human pulmonary diseases, and have been approved by the European Working Group on CFTR expression.

Perioperative abstinence from cigarettes: physiologic and clinical consequences.

PubMed

Warner, David O

2006-02-01

Chronic exposure to cigarette smoke produces profound changes in physiology that may alter responses to perioperative interventions and contribute to perioperative morbidity. Because of smoke-free policies in healthcare facilities, all smokers undergoing surgery are abstinent from cigarettes for at least some period of time so that all are in various stages of recovery from the effects of smoke. Understanding this recovery process will help perioperative physicians better treat these patients. This review examines current knowledge regarding how both short-term (duration ranging from hours to weeks) and long-term smoking cessation affects selected physiology and pathophysiology of particular relevance to perioperative outcomes and how these changes affect perioperative risk. It will also consider current evidence regarding how nicotine replacement therapy, a valuable adjunct to help patients maintain abstinence, may affect perioperative physiology.

Three-Dimensional Rotating Wall Vessel-Derived Cell Culture Models for Studying Virus-Host Interactions

PubMed Central

Gardner, Jameson K.; Herbst-Kralovetz, Melissa M.

2016-01-01

The key to better understanding complex virus-host interactions is the utilization of robust three-dimensional (3D) human cell cultures that effectively recapitulate native tissue architecture and model the microenvironment. A lack of physiologically-relevant animal models for many viruses has limited the elucidation of factors that influence viral pathogenesis and of complex host immune mechanisms. Conventional monolayer cell cultures may support viral infection, but are unable to form the tissue structures and complex microenvironments that mimic host physiology and, therefore, limiting their translational utility. The rotating wall vessel (RWV) bioreactor was designed by the National Aeronautics and Space Administration (NASA) to model microgravity and was later found to more accurately reproduce features of human tissue in vivo. Cells grown in RWV bioreactors develop in a low fluid-shear environment, which enables cells to form complex 3D tissue-like aggregates. A wide variety of human tissues (from neuronal to vaginal tissue) have been grown in RWV bioreactors and have been shown to support productive viral infection and physiological meaningful host responses. The in vivo-like characteristics and cellular features of the human 3D RWV-derived aggregates make them ideal model systems to effectively recapitulate pathophysiology and host responses necessary to conduct rigorous basic science, preclinical and translational studies. PMID:27834891

Biological Hydropersulfides and Related Polysulfides: A New Concept and Perspective in Redox Biology.

PubMed

Fukuto, Jon M; Ignarro, Louis J; Nagy, Peter; Wink, David A; Kevil, Christopher G; Feelisch, Martin; Cortese-Krott, Miriam M; Bianco, Christopher L; Kumagai, Yoshito; Hobbs, Adrian J; Lin, Joseph; Ida, Tomoaki; Akaike, Takaaki

2018-05-12

The chemical biology of thiols (RSH, e.g., cysteine and cysteine containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSS n H, RSS n R, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSS n H. RSSH of cysteine (Cys-SSH) has been found to be prevalent in mammalian systems along with Cys-SSH-containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys-SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evaluating physiological responses of plants to salinity stress

PubMed Central

Negrão, S.; Schmöckel, S. M.; Tester, M.

2017-01-01

Background Because soil salinity is a major abiotic constraint affecting crop yield, much research has been conducted to develop plants with improved salinity tolerance. Salinity stress impacts many aspects of a plant’s physiology, making it difficult to study in toto. Instead, it is more tractable to dissect the plant’s response into traits that are hypothesized to be involved in the overall tolerance of the plant to salinity. Scope and conclusions We discuss how to quantify the impact of salinity on different traits, such as relative growth rate, water relations, transpiration, transpiration use efficiency, ionic relations, photosynthesis, senescence, yield and yield components. We also suggest some guidelines to assist with the selection of appropriate experimental systems, imposition of salinity stress, and obtaining and analysing relevant physiological data using appropriate indices. We illustrate how these indices can be used to identify relationships amongst the proposed traits to identify which traits are the most important contributors to salinity tolerance. Salinity tolerance is complex and involves many genes, but progress has been made in studying the mechanisms underlying a plant’s response to salinity. Nevertheless, several previous studies on salinity tolerance could have benefited from improved experimental design. We hope that this paper will provide pertinent information to researchers on performing proficient assays and interpreting results from salinity tolerance experiments. PMID:27707746

Modeling the Normal and Neoplastic Cell Cycle with 'Realistic Boolean Genetic Networks': Their Application for Understanding Carcinogenesis and Assessing Therapeutic Strategies

NASA Technical Reports Server (NTRS)

Szallasi, Zoltan; Liang, Shoudan

2000-01-01

In this paper we show how Boolean genetic networks could be used to address complex problems in cancer biology. First, we describe a general strategy to generate Boolean genetic networks that incorporate all relevant biochemical and physiological parameters and cover all of their regulatory interactions in a deterministic manner. Second, we introduce 'realistic Boolean genetic networks' that produce time series measurements very similar to those detected in actual biological systems. Third, we outline a series of essential questions related to cancer biology and cancer therapy that could be addressed by the use of 'realistic Boolean genetic network' modeling.

Dosing antibiotics in neonates: review of the pharmacokinetic data.

PubMed

Rivera-Chaparro, Nazario D; Cohen-Wolkowiez, Michael; Greenberg, Rachel G

2017-09-01

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.

Hemodynamic analysis of patients in intensive care unit based on diffuse optical spectroscopic imaging system

NASA Astrophysics Data System (ADS)

Hsieh, Yao-Sheng; Wang, Chun-Yang; Ling, Yo-Wei; Chuang, Ming-Lung; Chuang, Ching-Cheng; Tsai, Jui-che; Lu, Chih-Wei; Sun, Chia-Wei

2010-02-01

Diffuse optical spectroscopic imaging (DOSI) is a technique to assess the spatial variation in absorption and scattering properties of the biological tissues and provides the monitoring of changes in concentrations of oxy-hemoglobin and deoxy-hemoglobin. In our preliminary study, the temporal tracings of hemodynamic oxygenation are measured with DOSI and venous occlusion test (VOT) from normal subjects, patients with heart failure and patients with sepsis in intensive care unit (ICU). In experiments, the obvious differences of hemodynamic signals can be observed among the three groups. The physiological relevance of VOT hemodynamics with respect to diseases is also discussed in this paper.

Epigenetics: a lasting impression?

PubMed

Biddie, Simon C; Lightman, Stafford L

2011-02-01

Epigenetics is the term that has been classically used to describe inheritable nongenetic factors that regulate genes. Although these factors were originally thought to act in a long time domain only, it is now clear that they can also be highly dynamic, changing over minutes. Transcription factors, including the glucocorticoid, oestrogen and androgen receptors, interact with these epigenetic mechanisms in a very dynamic manner to modify transcription of genes and consequently contribute to physiological processes, health and disease. Modern usage of the term epigenetics encompasses both longer-term and transient changes and is relevant to multiple biological systems. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization

PubMed Central

Barba, Anna Angela; d'Amore, Matteo

2013-01-01

Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested. PMID:24501580

INTESTINAL ALKALINE PHOSPHATASE: A SUMMARY OF ITS ROLE IN CLINICAL DISEASE

PubMed Central

Fawley, Jason; Gourlay, David

2016-01-01

Over the past few years, there is increasing evidence implicating a novel role for Intestinal Alkaline Phosphatase (IAP) in mitigating inflammatory mediated disorders. IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons, we sought to review recent research in both animal and humans on IAP’s physiologic function, mechanisms of action and current research in specific surgical diseases. PMID:27083970

Infection of the endothelium by members of the order Rickettsiales

PubMed Central

Valbuena, Gustavo; Walker, David H.

2010-01-01

Summary The vascular endothelium is the main target of a limited number of infectious agents; Rickettsia, Ehrlichia ruminantium, and Orientia tsutsugamushi are among them. These arthropod-transmitted obligately-intracellular bacteria cause serious systemic diseases that are not infrequently lethal. In this review, we discuss the bacterial biology, vector biology, and clinical aspects of these conditions with particular emphasis on the interactions of these bacteria with the vascular endothelium and how it responds to intracellular infection. The study of these bacteria in relevant in vivo models is likely to offer new insights into the physiology of the endothelium that have not been revealed by other models. PMID:19967137

Comparison of Caenorhabditis elegans NLP peptides with arthropod neuropeptides.

PubMed

Husson, Steven J; Lindemans, Marleen; Janssen, Tom; Schoofs, Liliane

2009-04-01

Neuropeptides are small messenger molecules that can be found in all metazoans, where they govern a diverse array of physiological processes. Because neuropeptides seem to be conserved among pest species, selected peptides can be considered as attractive targets for drug discovery. Much can be learned from the model system Caenorhabditis elegans because of the availability of a sequenced genome and state-of-the-art postgenomic technologies that enable characterization of endogenous peptides derived from neuropeptide-like protein (NLP) precursors. Here, we provide an overview of the NLP peptide family in C. elegans and discuss their resemblance with arthropod neuropeptides and their relevance for anthelmintic discovery.

Scoring systems for outcome prediction in patients with perforated peptic ulcer.

PubMed

Thorsen, Kenneth; Søreide, Jon Arne; Søreide, Kjetil

2013-04-10

Patients with perforated peptic ulcer (PPU) often present with acute, severe illness that carries a high risk for morbidity and mortality. Mortality ranges from 3-40% and several prognostic scoring systems have been suggested. The aim of this study was to review the available scoring systems for PPU patients, and to assert if there is evidence to prefer one to the other. We searched PubMed for the mesh terms "perforated peptic ulcer", "scoring systems", "risk factors", "outcome prediction", "mortality", "morbidity" and the combinations of these terms. In addition to relevant scores introduced in the past (e.g. Boey score), we included recent studies published between January 2000 and December 2012) that reported on scoring systems for prediction of morbidity and mortality in PPU patients. A total of ten different scoring systems used to predict outcome in PPU patients were identified; the Boey score, the Hacettepe score, the Jabalpur score the peptic ulcer perforation (PULP) score, the ASA score, the Charlson comorbidity index, the sepsis score, the Mannheim Peritonitis Index (MPI), the Acute physiology and chronic health evaluation II (APACHE II), the simplified acute physiology score II (SAPS II), the Mortality probability models II (MPM II), the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity physical sub-score (POSSUM-phys score). Only four of the scores were specifically constructed for PPU patients. In five studies the accuracy of outcome prediction of different scoring systems was evaluated by receiver operating characteristics curve (ROC) analysis, and the corresponding area under the curve (AUC) among studies compared. Considerable variation in performance both between different scores and between different studies was found, with the lowest and highest AUC reported between 0.63 and 0.98, respectively. While the Boey score and the ASA score are most commonly used to predict outcome for PPU patients, considerable variations in accuracy for outcome prediction were shown. Other scoring systems are hampered by a lack of validation or by their complexity that precludes routine clinical use. While the PULP score seems promising it needs external validation before widespread use.

GLO-Roots: an imaging platform enabling multidimensional characterization of soil-grown root systems

PubMed Central

Rellán-Álvarez, Rubén; Lobet, Guillaume; Lindner, Heike; Pradier, Pierre-Luc; Sebastian, Jose; Yee, Muh-Ching; Geng, Yu; Trontin, Charlotte; LaRue, Therese; Schrager-Lavelle, Amanda; Haney, Cara H; Nieu, Rita; Maloof, Julin; Vogel, John P; Dinneny, José R

2015-01-01

Root systems develop different root types that individually sense cues from their local environment and integrate this information with systemic signals. This complex multi-dimensional amalgam of inputs enables continuous adjustment of root growth rates, direction, and metabolic activity that define a dynamic physical network. Current methods for analyzing root biology balance physiological relevance with imaging capability. To bridge this divide, we developed an integrated-imaging system called Growth and Luminescence Observatory for Roots (GLO-Roots) that uses luminescence-based reporters to enable studies of root architecture and gene expression patterns in soil-grown, light-shielded roots. We have developed image analysis algorithms that allow the spatial integration of soil properties, gene expression, and root system architecture traits. We propose GLO-Roots as a system that has great utility in presenting environmental stimuli to roots in ways that evoke natural adaptive responses and in providing tools for studying the multi-dimensional nature of such processes. DOI: http://dx.doi.org/10.7554/eLife.07597.001 PMID:26287479

GLO-Roots: An imaging platform enabling multidimensional characterization of soil-grown root systems

DOE PAGES

Rellan-Alvarez, Ruben; Lobet, Guillaume; Lindner, Heike; ...

2015-08-19

Root systems develop different root types that individually sense cues from their local environment and integrate this information with systemic signals. This complex multi-dimensional amalgam of inputs enables continuous adjustment of root growth rates, direction, and metabolic activity that define a dynamic physical network. Current methods for analyzing root biology balance physiological relevance with imaging capability. To bridge this divide, we developed an integrated-imaging system called Growth and Luminescence Observatory for Roots (GLO-Roots) that uses luminescence-based reporters to enable studies of root architecture and gene expression patterns in soil-grown, light-shielded roots. We have developed image analysis algorithms that allow themore » spatial integration of soil properties, gene expression, and root system architecture traits. We propose GLO-Roots as a system that has great utility in presenting environmental stimuli to roots in ways that evoke natural adaptive responses and in providing tools for studying the multi-dimensional nature of such processes.« less

Physiology education in North American dental schools: the basic science survey series.

PubMed

Gautam, Medha; Shaw, David H; Pate, Ted D; Lambert, H Wayne

2014-06-01

As part of the Basic Science Survey Series for Dentistry, members of the American Dental Education Association (ADEA) Physiology, Pharmacology, and Therapeutics Section surveyed directors of physiology courses in North American dental schools. The survey was designed to assess, among other things, faculty affiliation and experience of course directors, teaching methods, general course content and emphasis, extent of interdisciplinary (shared) instruction, and impact of recent curricular changes. Responses were received from forty-four of sixty-seven (65.7 percent) U.S. and Canadian dental schools. The findings suggest the following: substantial variation exists in instructional hours, faculty affiliation, class size, and interdisciplinary nature of physiology courses; physiology course content emphasis is similar between schools; student contact hours in physiology, which have remained relatively stable in the past fifteen years, are starting to be reduced; recent curricular changes have often been directed towards enhancing the integrative and clinically relevant aspects of physiology instruction; and a trend toward innovative content delivery, such as use of computer-assisted instruction, is evident. Data from this study may be useful to physiology course directors, curriculum committees, and other dental educators with an interest in integrative and interprofessional education.

A Review of the Interactions between Alcohol and the Endocannabinoid System: Implications for Alcohol Dependence and Future Directions for Research

PubMed Central

Pava, Matthew J.; Woodward, John J.

2012-01-01

Over the past fifty years a significant body of evidence has been compiled suggesting an interaction between the endocannabinoid (EC) system and alcohol dependence. However, much of this work has been conducted only in the past two decades following the elucidation of the molecular constituents of the EC system that began with the serendipitous discovery of the cannabinoid 1 receptor (CB1). Since then, novel pharmacological and genetic tools have enabled researchers to manipulate select components of the EC system, to determine their contribution to the motivation to consume ethanol. From these preclinical studies, it is evident that CB1 contributes the motivational and reinforcing properties of ethanol, and chronic consumption of ethanol alters EC transmitter levels and CB1 expression in brain nuclei associated with addiction pathways. These results are augmented by in vitro and ex vivo studies showing that acute and chronic treatment with ethanol produces physiologically relevant alterations in the function of the EC system. This report provides a current and comprehensive review of the literature regarding the interactions between ethanol and the EC system. We begin be reviewing the studies published prior to the discovery of the EC system that compared the behavioral and physiological effects of cannabinoids with ethanol in addition to cross-tolerance between these drugs. Next, a brief overview of the molecular constituents of the EC system is provided as context for the subsequent review of more recent studies examining the interaction of ethanol with the EC system. These results are compiled into a summary providing a scheme for the known changes to the components of the EC system in different stages of alcohol dependence. Finally, future directions for research are discussed. PMID:22459871

The dynamic opponent relativity model: an integration and extension of capacity theory and existing theoretical perspectives on the neuropsychology of arousal and emotion.

PubMed

Comer, Clinton S; Harrison, Patti Kelly; Harrison, David W

2015-01-01

Arousal theory as discussed within the present paper refers to those mechanisms and neural systems involved in central nervous system activation and more specifically the systems involved in cortical activation. Historical progress in the evolution of arousal theory has led to a better understanding of the functional neural systems involved in arousal or activation processes and ultimately contributed much to our current theories of emotion. Despite evidence for the dynamic interplay between the left and right cerebral hemispheres, the concepts of cerebral balance and dynamic activation have been emphasized in the neuropsychological literature. A conceptual model is proposed herein that incorporates the unique contributions from multiple neuropsychological theories of arousal and emotion. It is argued that the cerebral hemispheres may play oppositional roles in emotion partially due to the differences in their functional specializations and in their persistence upon activation. In the presence of a threat or provocation, the right hemisphere may activate survival relevant responses partially derived from hemispheric specializations in arousal and emotional processing, including the mobilization of sympathetic drive to promote heightened blood pressure, heart rate, glucose mobilization and respiratory support necessary for the challenge. Oppositional processes and mechanisms are discussed, which may be relevant to the regulatory control over the survival response; however, the capacity of these systems is necessarily limited. A limited capacity mechanism is proposed, which is familiar within other physiological systems, including that providing for the prevention of muscular damage under exceptional demand. This capacity theory is proposed, wherein a link may be expected between exceptional stress within a neural system and damage to the neural system. These mechanisms are proposed to be relevant to emotion and emotional disorders. Discussion is provided on the possible role of currently applied therapeutic interventions for emotional disorders.

Translational Modeling in Schizophrenia: Predicting Human Dopamine D2 Receptor Occupancy.

PubMed

Johnson, Martin; Kozielska, Magdalena; Pilla Reddy, Venkatesh; Vermeulen, An; Barton, Hugh A; Grimwood, Sarah; de Greef, Rik; Groothuis, Geny M M; Danhof, Meindert; Proost, Johannes H

2016-04-01

To assess the ability of a previously developed hybrid physiology-based pharmacokinetic-pharmacodynamic (PBPKPD) model in rats to predict the dopamine D2 receptor occupancy (D2RO) in human striatum following administration of antipsychotic drugs. A hybrid PBPKPD model, previously developed using information on plasma concentrations, brain exposure and D2RO in rats, was used as the basis for the prediction of D2RO in human. The rat pharmacokinetic and brain physiology parameters were substituted with human population pharmacokinetic parameters and human physiological information. To predict the passive transport across the human blood-brain barrier, apparent permeability values were scaled based on rat and human brain endothelial surface area. Active efflux clearance in brain was scaled from rat to human using both human brain endothelial surface area and MDR1 expression. Binding constants at the D2 receptor were scaled based on the differences between in vitro and in vivo systems of the same species. The predictive power of this physiology-based approach was determined by comparing the D2RO predictions with the observed human D2RO of six antipsychotics at clinically relevant doses. Predicted human D2RO was in good agreement with clinically observed D2RO for five antipsychotics. Models using in vitro information predicted human D2RO well for most of the compounds evaluated in this analysis. However, human D2RO was under-predicted for haloperidol. The rat hybrid PBPKPD model structure, integrated with in vitro information and human pharmacokinetic and physiological information, constitutes a scientific basis to predict the time course of D2RO in man.

Heart Rate Variability Reflects the Natural History of Physiological Development in Healthy Children and Is Not Associated with Quality of Life

PubMed Central

Seifert, Georg; Calaminus, Gabriele; Wiener, Andreas; Cysarz, Dirk

2014-01-01

Background Quality of life (QoL), being the sum expression of diverse influencing factors, is not easy to determine. A clinically relevant option would be to identify and measure quality of life on the basis of physiological parameters which correlate plausibly and statistically with psychometrically measured QoL. Analysis of heart rate variability (HRV) offers readily measurable physiological parameters which could be of use here. A correlation of HRV with both course of disease and QoL has been reported in patients with chronic illness. Various psychometric instruments have been developed for use in paediatric oncology. The aim of this study was to obtain data on HRV and QoL and their correlations, initially in healthy children. Methods Holter ECG and quality of life were examined in 160 children and adolescents (72 male) aged between 8 and 18 years. QoL was determined with the established questionnaire PEDQoL. Standard parameters of HRV from the frequency domain were calculated and correlated with QoL domains using Spearman (nonparametric) correlation analysis. Results Minor but significant associations were revealed only with regard to the PEDQoL domain “autonomy” on the one hand and heart rate and HRV (e.g. MRR, MRRn, MRRd, HRV_ULF, SDNN) parameters which evidently reflect distinct physiological functions on the other. Conclusions In healthy children and adolescents we have a first indication that there is a correlation between parameters of HRV and QoL. However, to a greater extent, HRV reflects associated physiological processes of the autonomic nervous system. A higher correlation is more likely to be found in chronically ill children. PMID:24625571

Biochemical activity and multiple locations of particulate guanylate cyclase in Rhyacophila dorsalis acutidens (Insecta: Trichoptera) provide insights into the cGMP signalling pathway in Malpighian tubules.

PubMed

Secca, T; Sciaccaluga, M; Marra, A; Barberini, L; Bicchierai, M C

2011-04-01

In insect renal physiology, cGMP and cAMP have important regulatory roles. In Drosophila melanogaster, considered a good model for molecular physiology studies, and in other insects, cGMP and cAMP act as signalling molecules in the Malpighian tubules (MTs). However, many questions related to cyclic nucleotide functions are unsolved in principal cells (PC) and stellate cells (SC), the two cell types that compose the MT. In PC, despite the large body of information available on soluble guanylate cyclase (sGC) in the cGMP pathway, the functional circuit of particulate guanylate cyclase (pGC) remains obscure. In SC, on the other side, the synthesis and physiological role of the cGMP are still unknown. Our biochemical data regarding the presence of cyclic nucleotides in the MTs of Rhyacophila dorsalis acutidens revealed a cGMP level above the 50%, in comparison with the cAMP. The specific activity values for the membrane-bound guanylate cyclase were also recorded, implying that, besides the sGC, pGC is a physiologically relevant source of cGMP in MTs. Cytochemical studies showed ultrastructurally that there was a great deal of pGC on the basolateral membranes of both the principal and stellate cells. In addition, pGC was also detected in the contact zone between the two cell types and in the apical microvillar region of the stellate cells bordering the tubule lumen. The pGC signal is so well represented in PC and, unexpectedly in SC of MTs, that it is possible to hypothesize the existence of still uncharacterized physiological processes regulated by the pGC-cGMP system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Smart Vest: wearable multi-parameter remote physiological monitoring system.

PubMed

Pandian, P S; Mohanavelu, K; Safeer, K P; Kotresh, T M; Shakunthala, D T; Gopal, Parvati; Padaki, V C

2008-05-01

The wearable physiological monitoring system is a washable shirt, which uses an array of sensors connected to a central processing unit with firmware for continuously monitoring physiological signals. The data collected can be correlated to produce an overall picture of the wearer's health. In this paper, we discuss the wearable physiological monitoring system called 'Smart Vest'. The Smart Vest consists of a comfortable to wear vest with sensors integrated for monitoring physiological parameters, wearable data acquisition and processing hardware and remote monitoring station. The wearable data acquisition system is designed using microcontroller and interfaced with wireless communication and global positioning system (GPS) modules. The physiological signals monitored are electrocardiogram (ECG), photoplethysmogram (PPG), body temperature, blood pressure, galvanic skin response (GSR) and heart rate. The acquired physiological signals are sampled at 250samples/s, digitized at 12-bit resolution and transmitted wireless to a remote physiological monitoring station along with the geo-location of the wearer. The paper describes a prototype Smart Vest system used for remote monitoring of physiological parameters and the clinical validation of the data are also presented.

The potential anticancer effect of beta-blockers and the genetic variations involved in the interindividual difference.

PubMed

He, Ruo-Hui; He, Yi-Jing; Tang, Yong-Jun; Zhou, Hong-Hao; McLeod, Howard L; Liu, Jie

2016-01-01

β-ARs are extensively spread in different tissues of our body, which could be activated by neurotransmitters norepinephrine and epinephrine to mediate physiological function and abnormal states including cancer. Recently, β-AR blockers could have significant implications in cancer therapy. But the precise molecular mechanisms are far from being fully understood. Through identifying the β-AR system signal pathways relevant to cancer, we can understand the mechanisms of β-blockers used for cancer treatment. What's more, retrospective clinical data made β-blockers jump out of the traditional field of cardiovascular disease and strengthened our confidence in cancer therapy. At last, genetic studies of β-adrenergic system offered crucial genes to analyze the effects of polymorphisms on cancer susceptibility, therapy response and prognosis of cancer patients.

Neurobiology of Caenorhabditis elegans Locomotion: Where Do We Stand?

PubMed Central

Gjorgjieva, Julijana; Biron, David; Haspel, Gal

2014-01-01

Animals use a nervous system for locomotion in some stage of their life cycle. The nematode Caenorhabditis elegans, a major animal model for almost all fields of experimental biology, has long been used for detailed studies of genetic and physiological locomotion mechanisms. Of its 959 somatic cells, 302 are neurons that are identifiable by lineage, location, morphology, and neurochemistry in every adult hermaphrodite. Of those, 75 motoneurons innervate body wall muscles that provide the thrust during locomotion. In this Overview, we concentrate on the generation of either forward- or backward-directed motion during crawling and swimming. We describe locomotion behavior, the parts constituting the locomotion system, and the relevant neuronal connectivity. Because it is not yet fully understood how these components combine to generate locomotion, we discuss competing hypotheses and models. PMID:26955070

Scaling up our understanding of non-consumptive effects in insect systems

DOE PAGES

Hermann, Sara L.; Landis, Douglas A.

2017-04-06

Here, non-consumptive effects (NCEs) of predators on prey is an important topic in insect ecology with potential applications for pest management. NCEs are changes in prey behavior and physiology that aid in predation avoidance. While NCEs can have positive outcomes for prey survival there may also be negative consequences including increased stress and reduced growth. These effects can cascade through trophic systems influencing ecosystem function. Most NCEs have been studied at small spatial and temporal scales. However, recent studies show promise for the potential to manipulate NCEs for pest management. We suggest the next frontier for NCE studies includes manipulatingmore » the landscape of fear to improve pest control, which requires scaling-up to field and landscape levels, over ecologically relevant time frames.« less

Scaling up our understanding of non-consumptive effects in insect systems

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

Hermann, Sara L.; Landis, Douglas A.

Here, non-consumptive effects (NCEs) of predators on prey is an important topic in insect ecology with potential applications for pest management. NCEs are changes in prey behavior and physiology that aid in predation avoidance. While NCEs can have positive outcomes for prey survival there may also be negative consequences including increased stress and reduced growth. These effects can cascade through trophic systems influencing ecosystem function. Most NCEs have been studied at small spatial and temporal scales. However, recent studies show promise for the potential to manipulate NCEs for pest management. We suggest the next frontier for NCE studies includes manipulatingmore » the landscape of fear to improve pest control, which requires scaling-up to field and landscape levels, over ecologically relevant time frames.« less

Maximizing fluorescence collection efficiency in multiphoton microscopy

PubMed Central

Zinter, Joseph P.; Levene, Michael J.

2011-01-01

Understanding fluorescence propagation through a multiphoton microscope is of critical importance in designing high performance systems capable of deep tissue imaging. Optical models of a scattering tissue sample and the Olympus 20X 0.95NA microscope objective were used to simulate fluorescence propagation as a function of imaging depth for physiologically relevant scattering parameters. The spatio-angular distribution of fluorescence at the objective back aperture derived from these simulations was used to design a simple, maximally efficient post-objective fluorescence collection system. Monte Carlo simulations corroborated by data from experimental tissue phantoms demonstrate collection efficiency improvements of 50% – 90% over conventional, non-optimized fluorescence collection geometries at large imaging depths. Imaging performance was verified by imaging layer V neurons in mouse cortex to a depth of 850 μm. PMID:21934897

Detection of generalized synchronization using echo state networks

NASA Astrophysics Data System (ADS)

Ibáñez-Soria, D.; Garcia-Ojalvo, J.; Soria-Frisch, A.; Ruffini, G.

2018-03-01

Generalized synchronization between coupled dynamical systems is a phenomenon of relevance in applications that range from secure communications to physiological modelling. Here, we test the capabilities of reservoir computing and, in particular, echo state networks for the detection of generalized synchronization. A nonlinear dynamical system consisting of two coupled Rössler chaotic attractors is used to generate temporal series consisting of time-locked generalized synchronized sequences interleaved with unsynchronized ones. Correctly tuned, echo state networks are able to efficiently discriminate between unsynchronized and synchronized sequences even in the presence of relatively high levels of noise. Compared to other state-of-the-art techniques of synchronization detection, the online capabilities of the proposed Echo State Network based methodology make it a promising choice for real-time applications aiming to monitor dynamical synchronization changes in continuous signals.

Hitting the sweet spot-glycans as targets of fungal defense effector proteins.

PubMed

Künzler, Markus

2015-05-06

Organisms which rely solely on innate defense systems must combat a large number of antagonists with a comparably low number of defense effector molecules. As one solution of this problem, these organisms have evolved effector molecules targeting epitopes that are conserved between different antagonists of a specific taxon or, if possible, even of different taxa. In order to restrict the activity of the defense effector molecules to physiologically relevant taxa, these target epitopes should, on the other hand, be taxon-specific and easily accessible. Glycans fulfill all these requirements and are therefore a preferred target of defense effector molecules, in particular defense proteins. Here, we review this defense strategy using the example of the defense system of multicellular (filamentous) fungi against microbial competitors and animal predators.

Physiology of man and animals in the Tenth Five-Year Plan: Proceedings of the Thirteenth Congress of the I. P. Pavlov All-Union Physiological Society

NASA Technical Reports Server (NTRS)

Lange, K. A.

1980-01-01

Research in the field of animal and human physiology is reviewed. The following topics on problems of physiological science and related fields of knowledge are discussed: neurophysiology and higher nervous activity, physiology of sensory systems, physiology of visceral systems, evolutionary and ecological physiology, physiological cybernetics, computer application in physiology, information support of physiological research, history and theory of development of physiology. Also discussed were: artificial intelligence, physiological problems of reflex therapy, correlation of structure and function of the brain, adaptation and activity, microcirculation, and physiological studies in nerve and mental diseases.

Mammalian lipoxygenases and their biological relevance.

PubMed

Kuhn, Hartmut; Banthiya, Swathi; van Leyen, Klaus

2015-04-01

Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated not only in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOXs oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in the regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance". Copyright © 2014 Elsevier B.V. All rights reserved.

Low-shear modeled microgravity: a global environmental regulatory signal affecting bacterial gene expression, physiology, and pathogenesis

NASA Technical Reports Server (NTRS)

Nickerson, Cheryl A.; Ott, C. Mark; Wilson, James W.; Ramamurthy, Rajee; LeBlanc, Carly L.; Honer zu Bentrup, Kerstin; Hammond, Timothy; Pierson, Duane L.

2003-01-01

Bacteria inhabit an impressive variety of ecological niches and must adapt constantly to changing environmental conditions. While numerous environmental signals have been examined for their effect on bacteria, the effects of mechanical forces such as shear stress and gravity have only been investigated to a limited extent. However, several important studies have demonstrated a key role for the environmental signals of low shear and/or microgravity in the regulation of bacterial gene expression, physiology, and pathogenesis [Chem. Rec. 1 (2001) 333; Appl. Microbiol. Biotechnol. 54 (2000) 33; Appl. Environ. Microbiol. 63 (1997) 4090; J. Ind. Microbiol. 18 (1997) 22; Curr. Microbiol. 34(4) (1997) 199; Appl. Microbiol. Biotechnol. 56(3-4) (2001) 384; Infect Immun. 68(6) (2000) 3147; Cell 109(7) (2002) 913; Appl. Environ. Microbiol. 68(11) (2002) 5408; Proc. Natl. Acad. Sci. U. S. A. 99(21) (2002) 13807]. The response of bacteria to these environmental signals, which are similar to those encountered during prokaryotic life cycles, may provide insight into bacterial adaptations to physiologically relevant conditions. This review focuses on the current and potential future research trends aimed at understanding the effect of the mechanical forces of low shear and microgravity analogues on different bacterial parameters. In addition, this review also discusses the use of microgravity technology to generate physiologically relevant human tissue models for research in bacterial pathogenesis.

TRI-Worthy Projects for the Deep Space Gateway

NASA Astrophysics Data System (ADS)

Wotring, V. E.; Strangman, G. E.; Donoviel, D.

2018-02-01

Preparations for exploration will require exposure to the actual deep space environment. The new TRI for Space Health proposes innovative projects using real space radiation to make medically-relevant measurements affecting human physiology.

The relevance of phylogeny to studies of global change.

PubMed

Edwards, Erika J; Still, Christopher J; Donoghue, Michael J

2007-05-01

Phylogenetic thinking has infiltrated many areas of biological research, but has had little impact on studies of global ecology or climate change. Here, we illustrate how phylogenetic information can be relevant to understanding vegetation-atmosphere dynamics at ecosystem or global scales by re-analyzing a data set of carbonic anhydrase (CA) activity in leaves that was used to estimate terrestrial gross primary productivity. The original calculations relied on what appeared to be low CA activity exclusively in C4 grasses, but our analyses indicate that such activity might instead characterize the PACCAD grass lineage, which includes many widespread C3 species. We outline how phylogenetics can guide better taxon sampling of key physiological traits, and discuss how the emerging field of phyloinformatics presents a promising new framework for scaling from organism physiology to global processes.

Pathways of the Maillard reaction under physiological conditions.

PubMed

Henning, Christian; Glomb, Marcus A

2016-08-01

Initially investigated as a color formation process in thermally treated foods, nowadays, the relevance of the Maillard reaction in vivo is generally accepted. Many chronic and age-related diseases such as diabetes, uremia, atherosclerosis, cataractogenesis and Alzheimer's disease are associated with Maillard derived advanced glycation endproducts (AGEs) and α-dicarbonyl compounds as their most important precursors in terms of reactivity and abundance. However, the situation in vivo is very challenging, because Maillard chemistry is paralleled by enzymatic reactions which can lead to both, increases and decreases in certain AGEs. In addition, mechanistic findings established under the harsh conditions of food processing might not be valid under physiological conditions. The present review critically discusses the relevant α-dicarbonyl compounds as central intermediates of AGE formation in vivo with a special focus on fragmentation pathways leading to formation of amide-AGEs.

Anthocyanins and their gut metabolites reduce the adhesion of monocyte to TNFα-activated endothelial cells at physiologically relevant concentrations.

PubMed

Krga, Irena; Monfoulet, Laurent-Emmanuel; Konic-Ristic, Aleksandra; Mercier, Sylvie; Glibetic, Maria; Morand, Christine; Milenkovic, Dragan

2016-06-01

An increasing number of evidence suggests a protective role of dietary anthocyanins against cardiovascular diseases. Anthocyanins' extensive metabolism indicates that their metabolites could be responsible for the protective effects associated with consumption of anthocyanin-rich foods. The aim of this work was to investigate the effect of plasma anthocyanins and their metabolites on the adhesion of monocytes to TNFα-activated endothelial cells and on the expression of genes encoding cell adhesion molecules. Human umbilical vein endothelial cells (HUVECs) were exposed to circulating anthocyanins: cyanidin-3-arabinoside, cyanidin-3-galactoside, cyanidin-3-glucoside, delphinidin-3-glucoside, peonidin-3-glucoside, anthocyanin degradation product: 4-hydroxybenzaldehyde, or to their gut metabolites: protocatechuic, vanillic, ferulic and hippuric acid, at physiologically-relevant concentrations (0.1-2 μM) and time of exposure. Both anthocyanins and gut metabolites decreased the adhesion of monocytes to HUVECs, with a magnitude ranging from 18.1% to 47%. The mixture of anthocyanins and that of gut metabolites also reduced monocyte adhesion. However, no significant effect on the expression of genes encoding E-selectin, ICAM1 and VCAM1 was observed, suggesting that other molecular targets are involved in the observed effect. In conclusion, this study showed the potency of anthocyanins and their gut metabolites to modulate the adhesion of monocytes to endothelial cells, the initial step in atherosclerosis development, under physiologically-relevant conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Understanding the Onset of Health Impacts Caused by Disturbances

DTIC Science & Technology

2015-09-30

will define the PCoD Health stage in a way that we can start to integrate ecological and physiological PCoD research. OBJECTIVES In order to...for the first time assess the relevance of adipose transcriptomic and metabolomic biomarkers as measures relevant to PCoD in cetaceans. We aim to...individuals. APPROACH The Population Consequences of Disturbances ( PCoD ) paradigm provides a mean to link perturbations of individual phenotypic

Network Physiology: How Organ Systems Dynamically Interact

PubMed Central

Bartsch, Ronny P.; Liu, Kang K. L.; Bashan, Amir; Ivanov, Plamen Ch.

2015-01-01

We systematically study how diverse physiologic systems in the human organism dynamically interact and collectively behave to produce distinct physiologic states and functions. This is a fundamental question in the new interdisciplinary field of Network Physiology, and has not been previously explored. Introducing the novel concept of Time Delay Stability (TDS), we develop a computational approach to identify and quantify networks of physiologic interactions from long-term continuous, multi-channel physiological recordings. We also develop a physiologically-motivated visualization framework to map networks of dynamical organ interactions to graphical objects encoded with information about the coupling strength of network links quantified using the TDS measure. Applying a system-wide integrative approach, we identify distinct patterns in the network structure of organ interactions, as well as the frequency bands through which these interactions are mediated. We establish first maps representing physiologic organ network interactions and discover basic rules underlying the complex hierarchical reorganization in physiologic networks with transitions across physiologic states. Our findings demonstrate a direct association between network topology and physiologic function, and provide new insights into understanding how health and distinct physiologic states emerge from networked interactions among nonlinear multi-component complex systems. The presented here investigations are initial steps in building a first atlas of dynamic interactions among organ systems. PMID:26555073

Miniaturized Battery-Free Wireless Systems for Wearable Pulse Oximetry.

PubMed

Kim, Jeonghyun; Gutruf, Philipp; Chiarelli, Antonio M; Heo, Seung Yun; Cho, Kyoungyeon; Xie, Zhaoqian; Banks, Anthony; Han, Seungyoung; Jang, Kyung-In; Lee, Jung Woo; Lee, Kyu-Tae; Feng, Xue; Huang, Yonggang; Fabiani, Monica; Gratton, Gabriele; Paik, Ungyu; Rogers, John A

2017-01-05

Development of unconventional technologies for wireless collection, storage and analysis of quantitative, clinically relevant information on physiological status is of growing interest. Soft, biocompatible systems are widely regarded as important because they facilitate mounting on external (e.g. skin) and internal (e.g. heart, brain) surfaces of the body. Ultra-miniaturized, lightweight and battery-free devices have the potential to establish complementary options in bio-integration, where chronic interfaces (i.e. months) are possible on hard surfaces such as the fingernails and the teeth, with negligible risk for irritation or discomfort. Here we report materials and device concepts for flexible platforms that incorporate advanced optoelectronic functionality for applications in wireless capture and transmission of photoplethysmograms, including quantitative information on blood oxygenation, heart rate and heart rate variability. Specifically, reflectance pulse oximetry in conjunction with near-field communication (NFC) capabilities enables operation in thin, miniaturized flexible devices. Studies of the material aspects associated with the body interface, together with investigations of the radio frequency characteristics, the optoelectronic data acquisition approaches and the analysis methods capture all of the relevant engineering considerations. Demonstrations of operation on various locations of the body and quantitative comparisons to clinical gold standards establish the versatility and the measurement accuracy of these systems, respectively.

Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice

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

Sun Xiaoyun; Mi Lixin; Liu Jin

2011-08-15

Microcystins (MCs), the products of blooming algae Microcystis, are waterborne environmental toxins that have been implicated in the development of liver cancer, necrosis, and even fatal intrahepatic bleeding. Alternative protective approaches in addition to complete removal of MCs in drinking water are urgently needed. In our previous work, we found that sulforaphane (SFN) protects against microcystin-LR (MC-LR)-induced cytotoxicity by activating the NF-E2-related factor 2 (Nrf2)-mediated defensive response in human hepatoma (HepG2) and NIH 3T3 cells. The purpose of this study was to investigate and confirm efficacy the SFN-induced multi-mechanistic defense system against MC-induced hepatotoxicity in an animal model. We reportmore » that SFN protected against MC-LR-induced liver damage and animal death at a nontoxic and physiologically relevant dose in BALB/c mice. The protection by SFN included activities of anti-cytochrome P450 induction, anti-oxidation, anti-inflammation, and anti-apoptosis. Our results suggest that SFN may protect mice against MC-induced hepatotoxicity. This raises the possibility of a similar protective effect in human populations, particularly in developing countries where freshwaters are polluted by blooming algae. - Graphical abstract: Display Omitted Research Highlights: > SFN protected against MC-LR-induced liver damage and animal death in BALB/c mice. > The dose of SFN is at a nontoxic and physiologically relevant dose. > The protection included activities of anti-oxidation, anti-inflammation, and anti-apoptosis. > SFN may protect mice against MC-induced hepatotoxicity.« less

Ocular input for human melatonin regulation: relevance to breast cancer

NASA Technical Reports Server (NTRS)

Glickman, Gena; Levin, Robert; Brainard, George C.

2002-01-01

The impact of breast cancer on women across the world has been extensive and severe. As prevalence of breast cancer is greatest in industrialized regions, exposure to light at night has been proposed as a potential risk factor. This theory is supported by the epidemiological observations of decreased breast cancer in blind women and increased breast cancer in women who do shift-work. In addition, human, animal and in vitro studies which have investigated the melatonin-cancer dynamic indicate an apparent relationship between light, melatonin and cancer, albeit complex. Recent developments in understanding melatonin regulation by light in humans are examined, with particular attention to factors that contribute to the sensitivity of the light-induced melatonin suppression response. Specifically, the role of spectral characteristics of light is addressed, and recent relevant action spectrum studies in humans and other mammalian species are discussed. Across five action spectra for circadian and other non-visual responses, a peak sensitivity between 446-484 nm was identified. Under highly controlled exposure circumstances, less than 1 lux of monochromatic light elicited a significant suppression of nocturnal melatonin. In view of the possible link between light exposure, melatonin suppression and cancer risk, it is important to continue to identify the basic related ocular physiology. Visual performance, rather than circadian function, has been the primary focus of architectural lighting systems. It is now necessary to reevaluate lighting strategies, with consideration of circadian influences, in an effort to maximize physiological homeostasis and health.

Medicating the environment: assessing risks of pharmaceuticals to wildlife and ecosystems.

PubMed

Arnold, Kathryn E; Brown, A Ross; Ankley, Gerald T; Sumpter, John P

2014-11-19

Global pharmaceutical consumption is rising with the growing and ageing human population and more intensive food production. Recent studies have revealed pharmaceutical residues in a wide range of ecosystems and organisms. Environmental concentrations are often low, but pharmaceuticals typically are designed to have biological effects at low doses, acting on physiological systems that can be evolutionarily conserved across taxa. This Theme Issue introduces the latest research investigating the risks of environmentally relevant concentrations of pharmaceuticals to vertebrate wildlife. We take a holistic, global view of environmental exposure to pharmaceuticals encompassing terrestrial, freshwater and marine ecosystems in high- and low-income countries. Based on both field and laboratory data, the evidence for and relevance of changes to physiology and behaviour, in addition to mortality and reproductive effects, are examined in terms of the population- and community-level consequences of pharmaceutical exposure on wildlife. Studies on uptake, trophic transfer and indirect effects of pharmaceuticals acting via food webs are presented. Given the logistical and ethical complexities of research in this area, several papers focus on techniques for prioritizing which compounds are most likely to harm wildlife and how modelling approaches can make predictions about the bioavailability, metabolism and toxicity of pharmaceuticals in non-target species. This Theme Issue aims to help clarify the uncertainties, highlight opportunities and inform ongoing scientific and policy debates on the impacts of pharmaceuticals in the environment. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Ocular input for human melatonin regulation: relevance to breast cancer.

PubMed

Glickman, Gena; Levin, Robert; Brainard, George C

2002-07-01

The impact of breast cancer on women across the world has been extensive and severe. As prevalence of breast cancer is greatest in industrialized regions, exposure to light at night has been proposed as a potential risk factor. This theory is supported by the epidemiological observations of decreased breast cancer in blind women and increased breast cancer in women who do shift-work. In addition, human, animal and in vitro studies which have investigated the melatonin-cancer dynamic indicate an apparent relationship between light, melatonin and cancer, albeit complex. Recent developments in understanding melatonin regulation by light in humans are examined, with particular attention to factors that contribute to the sensitivity of the light-induced melatonin suppression response. Specifically, the role of spectral characteristics of light is addressed, and recent relevant action spectrum studies in humans and other mammalian species are discussed. Across five action spectra for circadian and other non-visual responses, a peak sensitivity between 446-484 nm was identified. Under highly controlled exposure circumstances, less than 1 lux of monochromatic light elicited a significant suppression of nocturnal melatonin. In view of the possible link between light exposure, melatonin suppression and cancer risk, it is important to continue to identify the basic related ocular physiology. Visual performance, rather than circadian function, has been the primary focus of architectural lighting systems. It is now necessary to reevaluate lighting strategies, with consideration of circadian influences, in an effort to maximize physiological homeostasis and health.

The recovery time course of the endothelial-cell glycocalyx in vivo and its implications in vitro

PubMed Central

Potter, Daniel R.; Jiang, John; Damiano, Edward R.

2009-01-01

Compelling evidence continues to emerge suggesting that the glycocalyx surface layer on vascular endothelial cells plays a determining role in numerous physiological processes including inflammation, microvascular permeability, and endothelial mechanotransduction. Previous research has shown that enzymes degrade the glycocalyx, while inflammation causes shedding of the layer. To track the endogenous recovery of the glycocalyx in vivo, we used fluorescent micro-particle image velocimetry (µ-PIV) in mouse cremaster-muscle venules to estimate the hydrodynamically relevant glycocalyx thickness 1, 3, 5, and 7 days after enzymatic or cytokine-mediated degradation of the layer. Results indicate that after acute degradation of the glycocalyx, 5–7 days are required for the layer to endogenously restore itself to its native hydrodynamically relevant thickness in vivo. In light of these findings, and since demonstrable evidence has emerged that standard cell-culture conditions are not conducive to providing the environment and/or cellular conditions necessary to produce and maintain a physiologically relevant cell-surface glycocalyx in vitro, we sought to determine if merely the passage of time would be sufficient to promote the production of a hydrodynamically relevant glycocalyx on a confluent monolayer of human umbilical vein endothelial cells (HUVECs). Using µ-PIV, we found that the hydrodynamically relevant glycocalyx was substantially absent 7 days post-confluence on HUVEC-lined cylindrical collagen microchannels maintained under standard culture conditions. Thus it remains to be determined how a hydrodynamically relevant glycocalyx surface layer can be synthesized and maintained in culture before the endothelial-cell culture model can be used to elucidate glycocalyx-mediated mechanisms of endothelial-cell function. PMID:19443840

A new flow-regulating cell type in the Demosponge Tethya wilhelma - functional cellular anatomy of a leuconoid canal system.

PubMed

Hammel, Jörg U; Nickel, Michael

2014-01-01

Demosponges possess a leucon-type canal system which is characterized by a highly complex network of canal segments and choanocyte chambers. As sponges are sessile filter feeders, their aquiferous system plays an essential role in various fundamental physiological processes. Due to the morphological and architectural complexity of the canal system and the strong interdependence between flow conditions and anatomy, our understanding of fluid dynamics throughout leuconoid systems is patchy. This paper provides comprehensive morphometric data on the general architecture of the canal system, flow measurements and detailed cellular anatomical information to help fill in the gaps. We focus on the functional cellular anatomy of the aquiferous system and discuss all relevant cell types in the context of hydrodynamic and evolutionary constraints. Our analysis is based on the canal system of the tropical demosponge Tethya wilhelma, which we studied using scanning electron microscopy. We found a hitherto undescribed cell type, the reticuloapopylocyte, which is involved in flow regulation in the choanocyte chambers. It has a highly fenestrated, grid-like morphology and covers the apopylar opening. The minute opening of the reticuloapopylocyte occurs in an opened, intermediate and closed state. These states permit a gradual regulation of the total apopylar opening area. In this paper the three states are included in a theoretical study into flow conditions which aims to draw a link between functional cellular anatomy, the hydrodynamic situation and the regular body contractions seen in T. wilhelma. This provides a basis for new hypotheses regarding the function of bypass elements and the role of hydrostatic pressure in body contractions. Our study provides insights into the local and global flow conditions in the sponge canal system and thus enhances current understanding of related physiological processes.

A New Flow-Regulating Cell Type in the Demosponge Tethya wilhelma – Functional Cellular Anatomy of a Leuconoid Canal System

PubMed Central

Hammel, Jörg U.; Nickel, Michael

2014-01-01

Demosponges possess a leucon-type canal system which is characterized by a highly complex network of canal segments and choanocyte chambers. As sponges are sessile filter feeders, their aquiferous system plays an essential role in various fundamental physiological processes. Due to the morphological and architectural complexity of the canal system and the strong interdependence between flow conditions and anatomy, our understanding of fluid dynamics throughout leuconoid systems is patchy. This paper provides comprehensive morphometric data on the general architecture of the canal system, flow measurements and detailed cellular anatomical information to help fill in the gaps. We focus on the functional cellular anatomy of the aquiferous system and discuss all relevant cell types in the context of hydrodynamic and evolutionary constraints. Our analysis is based on the canal system of the tropical demosponge Tethya wilhelma, which we studied using scanning electron microscopy. We found a hitherto undescribed cell type, the reticuloapopylocyte, which is involved in flow regulation in the choanocyte chambers. It has a highly fenestrated, grid-like morphology and covers the apopylar opening. The minute opening of the reticuloapopylocyte occurs in an opened, intermediate and closed state. These states permit a gradual regulation of the total apopylar opening area. In this paper the three states are included in a theoretical study into flow conditions which aims to draw a link between functional cellular anatomy, the hydrodynamic situation and the regular body contractions seen in T. wilhelma. This provides a basis for new hypotheses regarding the function of bypass elements and the role of hydrostatic pressure in body contractions. Our study provides insights into the local and global flow conditions in the sponge canal system and thus enhances current understanding of related physiological processes. PMID:25409176

Method and System for Physiologically Modulating Videogames and Simulations which Use Gesture and Body Image Sensing Control Input Devices

NASA Technical Reports Server (NTRS)

Pope, Alan T. (Inventor); Stephens, Chad L. (Inventor); Habowski, Tyler (Inventor)

2017-01-01

Method for physiologically modulating videogames and simulations includes utilizing input from a motion-sensing video game system and input from a physiological signal acquisition device. The inputs from the physiological signal sensors are utilized to change the response of a user's avatar to inputs from the motion-sensing sensors. The motion-sensing system comprises a 3D sensor system having full-body 3D motion capture of a user's body. This arrangement encourages health-enhancing physiological self-regulation skills or therapeutic amplification of healthful physiological characteristics. The system provides increased motivation for users to utilize biofeedback as may be desired for treatment of various conditions.

Emerging In Vitro Liver Technologies for Drug Metabolism and Inter-Organ Interactions

PubMed Central

Bale, Shyam Sundhar; Moore, Laura

2016-01-01

In vitro liver models provide essential information for evaluating drug metabolism, metabolite formation, and hepatotoxicity. Interfacing liver models with other organ models could provide insights into the desirable as well as unintended systemic side effects of therapeutic agents and their metabolites. Such information is invaluable for drug screening processes particularly in the context of secondary organ toxicity. While interfacing of liver models with other organ models has been achieved, platforms that effectively provide human-relevant precise information are needed. In this concise review, we discuss the current state-of-the-art of liver-based multiorgan cell culture platforms primarily from a drug and metabolite perspective, and highlight the importance of media-to-cell ratio in interfacing liver models with other organ models. In addition, we briefly discuss issues related to development of optimal liver models that include recent advances in hepatic cell lines, stem cells, and challenges associated with primary hepatocyte-based liver models. Liver-based multiorgan models that achieve physiologically relevant coupling of different organ models can have a broad impact in evaluating drug efficacy and toxicity, as well as mechanistic investigation of human-relevant disease conditions. PMID:27049038

Hemostasis in the Very Young.

PubMed

Kenet, Gili; Barg, Assaf Arie; Nowak-Göttl, Ulrike

2018-06-18

Hemostasis is a dynamic process that starts in utero. The coagulation system evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins in early life compared with adulthood. This concept, known as "developmental hemostasis," has important biological and clinical implications. Overall, impaired platelet function, along with physiologically reduced levels of vitamin K-dependent and contact coagulation factors, may cause poorer clot firmness even in healthy neonates. However, increased activity of von Willebrand factor and low levels of coagulation inhibitors that promote hemostasis counterbalance the delicate and immature hemostatic system. Since this hemostatic system has little reserve capacity, preterm neonates or sick infants are extremely vulnerable and predisposed to either hemorrhagic or thrombotic complications. This review will address the concept and manifestations of developmental hemostasis with respect to clinical disease phenotypes. It will discuss bleeding diagnosis in neonates, dealing especially with the devastating complications of intracerebral and pulmonary hemorrhage in preterm infants. Neonates, especially the sickest preterm ones, are also extremely susceptible to thrombotic complications; thus, thrombosis in neonates will be reviewed, with special focus on arterial ischemic perinatal stroke. Based on the concept of developmental hemostasis, the phenotypes of clinically relevant bleeding or thrombotic disorders among neonates may differ from those of older infants and children. Treatment options for these conditions will be suggested and reviewed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

EGFR transactivation: mechanisms, pathophysiology and potential therapies in cardiovascular system

PubMed Central

Forrester, Steven J.; Kawai, Tatsuo; Elliott, Katherine J.; O’Brien, Shannon; Thomas, Walter; Harris, Raymond C.; Eguchi, Satoru

2017-01-01

Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications. PMID:26566153

Anesthesia and concussion.

PubMed

Tasker, Robert C

2017-06-01

As clinicians preparing patients for general anesthesia, should we consider the possibility of concussion in our elective operative patients? If so, why is this necessary? Is it possible that exposure to an anesthetic is detrimental to recovery from concussion? If so, what should we do about the imperative/urgency for surgery? No answers are promised in this review. Rather, the focus is on the questions and approaches taken in the recent literature, as well as highlighting a need for more research. Surgery, pain and general anesthesia all influence autonomic nervous system responses. Intravenous and inhalational anesthetic agents are also known to have variable effects on the cerebrovascular reactivity (CVR) to carbon dioxide (CO2). This review adds to this general information the recent, specific physiologic alterations seen after concussion in autonomic system function and the CVR to CO2. This review provides a perspective about autonomic nervous system function and cerebrovascular effects of concussion, and some relevant clinical issues that warrant further clinical study.

Advancements in zebrafish applications for 21st century toxicology.

PubMed

Garcia, Gloria R; Noyes, Pamela D; Tanguay, Robert L

2016-05-01

The zebrafish model is the only available high-throughput vertebrate assessment system, and it is uniquely suited for studies of in vivo cell biology. A sequenced and annotated genome has revealed a large degree of evolutionary conservation in comparison to the human genome. Due to our shared evolutionary history, the anatomical and physiological features of fish are highly homologous to humans, which facilitates studies relevant to human health. In addition, zebrafish provide a very unique vertebrate data stream that allows researchers to anchor hypotheses at the biochemical, genetic, and cellular levels to observations at the structural, functional, and behavioral level in a high-throughput format. In this review, we will draw heavily from toxicological studies to highlight advances in zebrafish high-throughput systems. Breakthroughs in transgenic/reporter lines and methods for genetic manipulation, such as the CRISPR-Cas9 system, will be comprised of reports across diverse disciplines. Copyright © 2016 Elsevier Inc. All rights reserved.

Advancements in zebrafish applications for 21st century toxicology

PubMed Central

Garcia, Gloria R.; Noyes, Pamela D.; Tanguay, Robert L.

2016-01-01

The zebrafish model is the only available high-throughput vertebrate assessment system, and it is uniquely suited for studies of in vivo cell biology. A sequenced and annotated genome has revealed a large degree of evolutionary conservation in comparison to the human genome. Due to our shared evolutionary history, the anatomical and physiological features of fish are highly homologous to humans, which facilitates studies relevant to human health. In addition, zebrafish provide a very unique vertebrate data stream that allows researchers to anchor hypotheses at the biochemical, genetic, and cellular levels to observations at the structural, functional, and behavioral level in a high-throughput format. In this review, we will draw heavily from toxicological studies to highlight advances in zebrafish high-throughput systems. Breakthroughs in transgenic/reporter lines and methods for genetic manipulation, such as the CRISPR-Cas9 system, will be comprised of reports across diverse disciplines. PMID:27016469

Childhood Stuttering – Where are we and Where are we going?

PubMed Central

Smith, Anne; Weber, Christine

2017-01-01

Remarkable progress has been made over the past two decades in expanding our understanding of the behavioral, peripheral physiological, and central neurophysiological bases of stuttering in early childhood. It is clear that stuttering is a neurodevelopmental disorder characterized by atypical development of speech motor planning and execution networks. The speech motor system must interact in complex ways with neural systems mediating language, other cognitive, and emotional processes. During the time window when stuttering typically appears and follows its path to either recovery or persistence, all of these neurobehavioral systems are undergoing rapid and dramatic developmental changes. We summarize our current understanding of the various developmental trajectories relevant for the understanding of stuttering in early childhood. We also present theoretical and experimental approaches that we believe will be optimal for even more rapid progress toward developing better and more targeted treatment for stuttering in the preschool children who are more likely to persist in stuttering. PMID:27701705

Scoring systems for outcome prediction in patients with perforated peptic ulcer

PubMed Central

2013-01-01

Background Patients with perforated peptic ulcer (PPU) often present with acute, severe illness that carries a high risk for morbidity and mortality. Mortality ranges from 3-40% and several prognostic scoring systems have been suggested. The aim of this study was to review the available scoring systems for PPU patients, and to assert if there is evidence to prefer one to the other. Material and methods We searched PubMed for the mesh terms “perforated peptic ulcer”, “scoring systems”, “risk factors”, ”outcome prediction”, “mortality”, ”morbidity” and the combinations of these terms. In addition to relevant scores introduced in the past (e.g. Boey score), we included recent studies published between January 2000 and December 2012) that reported on scoring systems for prediction of morbidity and mortality in PPU patients. Results A total of ten different scoring systems used to predict outcome in PPU patients were identified; the Boey score, the Hacettepe score, the Jabalpur score the peptic ulcer perforation (PULP) score, the ASA score, the Charlson comorbidity index, the sepsis score, the Mannheim Peritonitis Index (MPI), the Acute physiology and chronic health evaluation II (APACHE II), the simplified acute physiology score II (SAPS II), the Mortality probability models II (MPM II), the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity physical sub-score (POSSUM-phys score). Only four of the scores were specifically constructed for PPU patients. In five studies the accuracy of outcome prediction of different scoring systems was evaluated by receiver operating characteristics curve (ROC) analysis, and the corresponding area under the curve (AUC) among studies compared. Considerable variation in performance both between different scores and between different studies was found, with the lowest and highest AUC reported between 0.63 and 0.98, respectively. Conclusion While the Boey score and the ASA score are most commonly used to predict outcome for PPU patients, considerable variations in accuracy for outcome prediction were shown. Other scoring systems are hampered by a lack of validation or by their complexity that precludes routine clinical use. While the PULP score seems promising it needs external validation before widespread use. PMID:23574922

A brief survey of aquaporins and their implications for renal physiology.

PubMed

Gade, Wayne; Robinson, Brooke

2006-01-01

Aquaporins (AQPs) are an important family of proteins that efficiently channel water through the cell membranes. Although water can diffuse across biological membranes at measurable rates, physiologists had long predicted the existence of channels to facilitate rapid reabsorption of water by renal tubular cells. With AQPs present, water can "gush" through the membrane at the extraordinary rate of three billion water molecules per second per aquaporin channel. In their absence, water only trickles across the hydrophobic lipid bilayers of cell membranes. Aquaporins have fascinated researchers over the last decade, culminating in the 2003 Nobel Prize for Chemistry given to their discoverer, Dr. Peter Agre. During the 1990s, scientists identified and characterized members of the mammalian aquaporin family, now designated as AQP0 through AQP10. AQPs are also found in many plant and bacterial species. However, their relevance to the clinical laboratory is only recently emerging. Dr. Agre's Nobel symposium address provides an excellent mini-review of aquaporins in medicine. Our understanding of renal physiology and pathophysiology has advanced greatly as we account for the subtle implications of various AQP systems. For example, nephrogenic diabetes insipidus (NDI), the inability to produce concentrated urine, can result from several different malfunctions in the AQP2 system controlled by anti-diuretic hormone (ADH). Virtually all mammalian cells incorporate aquaporins into their cell membranes, and many cells produce multiple aquaporins, each with a specific function. It is therefore not surprising that malfunctions have important clinical conditions. The present article discusses the implications of aquaporins for renal physiology, while the accompanying article is focused on the clinical aspects of aquaporins.

Interactive computer-assisted instruction in acid-base physiology for mobile computer platforms.

PubMed

Longmuir, Kenneth J

2014-03-01

In this project, the traditional lecture hall presentation of acid-base physiology in the first-year medical school curriculum was replaced by interactive, computer-assisted instruction designed primarily for the iPad and other mobile computer platforms. Three learning modules were developed, each with ∼20 screens of information, on the subjects of the CO2-bicarbonate buffer system, other body buffer systems, and acid-base disorders. Five clinical case modules were also developed. For the learning modules, the interactive, active learning activities were primarily step-by-step learner control of explanations of complex physiological concepts, usually presented graphically. For the clinical cases, the active learning activities were primarily question-and-answer exercises that related clinical findings to the relevant basic science concepts. The student response was remarkably positive, with the interactive, active learning aspect of the instruction cited as the most important feature. Also, students cited the self-paced instruction, extensive use of interactive graphics, and side-by-side presentation of text and graphics as positive features. Most students reported that it took less time to study the subject matter with this online instruction compared with subject matter presented in the lecture hall. However, the approach to learning was highly examination driven, with most students delaying the study of the subject matter until a few days before the scheduled examination. Wider implementation of active learning computer-assisted instruction will require that instructors present subject matter interactively, that students fully embrace the responsibilities of independent learning, and that institutional administrations measure instructional effort by criteria other than scheduled hours of instruction.

Effects of episodic low aragonite saturation and elevated temperature on the physiology of Stylophora pistillata

NASA Astrophysics Data System (ADS)

Lürig, M.; Kunzmann, A.

2015-05-01

As global climate change is predicted to gradually alter the oceans' carbonate system and water temperature, knowledge about the effects an altered marine environment has on the physiology of reef building (hermatypic) coral species is more widely established. However, although it is recognized that seawater temperature and the carbonate system of a coral reef can change rapidly and with great amplitude, little is known about how the interaction of these natural fluctuations with long term effects of climate change may affect the metabolism and productivity of hermatypic corals. To investigate this, we acclimated the hermatypic coral Stylophora pistillata to a "worst case" scenario for carbon dioxide emissions (aragonite saturation state [ΩARAG] = 1.6), and tested how exposure to short term (24 h) elevated temperature (+ 3 °C) and further lowered ΩARAG (-1 unit) affected its photosynthesis and respiration. While episodic exposure to very low ΩARAG had only little effect on S. pistillata's physiology, short term heat stress caused a shift from net oxygen production to consumption and partial coral bleaching. Higher gross coral respiration, and lowered photosynthetic activity under episodically elevated temperature may have been the result of photoinhibition and partial coral bleaching. These findings suggest that fluctuating environmental conditions in combination with a low ΩARAG background signal may impair basic metabolic processes in calcifying corals. In a future high-CO2 world short term stress could be relevant for reef ecosystem processes, and may affect the resilience of coral reefs to other external influences and effects of climate change.

Outdoor thermal physiology along human pathways: a study using a wearable measurement system

NASA Astrophysics Data System (ADS)

Nakayoshi, Makoto; Kanda, Manabu; Shi, Rui; de Dear, Richard

2015-05-01

An outdoor summer study on thermal physiology along subjects' pathways was conducted in a Japanese city using a unique wearable measurement system that measures all the relevant thermal variables: ambient temperature, humidity, wind speed ( U) and short/long-wave radiation ( S and L), along with some physio-psychological parameters: skin temperature ( T skin), pulse rate, subjective thermal sensation and state of body motion. U, S and L were measured using a globe anemo-radiometer adapted use with pedestrian subjects. The subjects were 26 healthy Japanese adults (14 males, 12 females) ranging from 23 to 74 years in age. Each subject wore a set of instruments that recorded individual microclimate and physiological responses along a designated pedestrian route that traversed various urban textures. The subjects experienced varying thermal environments that could not be represented by fixed-point routine observational data. S fluctuated significantly reflecting the mixture of sunlit/shade distributions within complex urban morphology. U was generally low within urban canyons due to drag by urban obstacles such as buildings but the subjects' movements enhanced convective heat exchanges with the atmosphere, leading to a drop in T skin. The amount of sweating increased as standard effective temperature (SET*) increased. A clear dependence of sweating on gender and body size was found; males sweated more than females; overweight subjects sweated more than standard/underweight subjects. T skin had a linear relationship with SET* and a similarly clear dependence on gender and body size differences. T skin of the higher-sweating groups was lower than that of the lower-sweating groups, reflecting differences in evaporative cooling by perspiration.

[Physiology in Relation to Anesthesia Practice: Preface and Comments].

PubMed

Yamada, Yoshitsugu

2016-05-01

It has been long recognized that anesthesia practice is profoundly based in physiology. With the advance of the technology of imaging, measurement and information, a serious gap has emerged between anesthesia mainly handling gross systemic parameters and molecular physiology. One of the main reasons is the lack of establishment of integration approach. This special series of reviews deals with systems physiology covering respiratory, cardiovascular, and nervous systems. It also includes metabolism, and fluid, acid-base, and electrolyte balance. Each review focuses on several physiological concepts in each area, explaining current understanding and limits of the concepts based on the new findings. They reaffirm the importance of applying physiological inference in anesthesia practice and underscore the needs of advancement of systems physiology.

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System.

PubMed

Okaty, Benjamin W; Freret, Morgan E; Rood, Benjamin D; Brust, Rachael D; Hennessy, Morgan L; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N; Dymecki, Susan M

2015-11-18

Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-seq to deconstruct the mouse 5HT system at multiple levels of granularity-from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal principles underlying system organization, 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers sertonergic subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. Copyright © 2015 Elsevier Inc. All rights reserved.

Multi-Scale Molecular Deconstruction of the Serotonin Neuron System

PubMed Central

Okaty, Benjamin W.; Freret, Morgan E.; Rood, Benjamin D.; Brust, Rachael D.; Hennessy, Morgan L.; deBairos, Danielle; Kim, Jun Chul; Cook, Melloni N.; Dymecki, Susan M.

2016-01-01

Summary Serotonergic (5HT) neurons modulate diverse behaviors and physiology and are implicated in distinct clinical disorders. Corresponding diversity in 5HT neuronal phenotypes is becoming apparent and is likely rooted in molecular differences, yet a comprehensive approach characterizing molecular variation across the 5HT system is lacking, as is concomitant linkage to cellular phenotypes. Here we combine intersectional fate mapping, neuron sorting, and genome-wide RNA-Seq to deconstruct the mouse 5HT system at multiple levels of granularity—from anatomy, to genetic sublineages, to single neurons. Our unbiased analyses reveal: principles underlying system organization, novel 5HT neuron subtypes, constellations of differentially expressed genes distinguishing subtypes, and predictions of subtype-specific functions. Using electrophysiology, subtype-specific neuron silencing, and conditional gene knockout, we show that these molecularly defined 5HT neuron subtypes are functionally distinct. Collectively, this resource classifies molecular diversity across the 5HT system and discovers new subtypes, markers, organizing principles, and subtype-specific functions with potential disease relevance. PMID:26549332

Identification and Evaluation of Integration and Cross Cutting Issues Across HRP Risks

NASA Technical Reports Server (NTRS)

Steinberg, S. L.; Shelhamer, Mark

2015-01-01

The HRP Integrated Research Plan contains the research plans for the 32 risks requiring research to characterize and mitigate. These risks to human health and performance in spaceflight are identified by evidence and each one focuses on a single aspect of human physiology or performance. They are further categorized by aspects of the spaceflight environment, such as altered gravity or space radiation, that that play a major role in their likelihood and consequence. From its inception the "integrate" in the Research Plan has denoted the integrated nature of risks to human health and performance, the connectedness of physiological systems within the human body regardless of the spaceflight environment, and the integrated response of the human body to the spaceflight environment. Common characteristics of the spaceflight environment include altered gravity, atmospheres and light/dark cycles, space radiation, isolation, noise, and periods of high or low workload. Long term exposure to this unique environment produces a suite of physiological effects such as stress; vision, neurocognitive and anthropometric changes; circadian misalignment; fluid shifts, deconditioning; immune dysregulation; and altered nutritional requirements. Matrix diagraming was used to systematically identify, analyze and rate the many-to-many relationships between environmental characteristics and the suite of physiological effects. It was also to identify patterns in the relationships of common physiological effects to each other. Analyses of patterns or relationships in these diagrams help to identify issues that cut across multiple risks. Cross cutting issues benefit from a multidisciplinary approach that synthesizes concepts or data from two or more disciplines to identify and characterize risk factors or develop countermeasures relevant to multiple risks. They also help to illuminate possible problem areas that may arise when a countermeasure impacts risks other than those which it was developed to mitigate, or identify groupings of physiological changes that are likely to occur that may impact the overall risk posture.

Optical tracking of embryonic vertebrates behavioural responses using automated time-resolved video-microscopy system

NASA Astrophysics Data System (ADS)

Walpitagama, Milanga; Kaslin, Jan; Nugegoda, Dayanthi; Wlodkowic, Donald

2016-12-01

The fish embryo toxicity (FET) biotest performed on embryos of zebrafish (Danio rerio) has gained significant popularity as a rapid and inexpensive alternative approach in chemical hazard and risk assessment. The FET was designed to evaluate acute toxicity on embryonic stages of fish exposed to the test chemical. The current standard, similar to most traditional methods for evaluating aquatic toxicity provides, however, little understanding of effects of environmentally relevant concentrations of chemical stressors. We postulate that significant environmental effects such as altered motor functions, physiological alterations reflected in heart rate, effects on development and reproduction can occur at sub-lethal concentrations well below than LC10. Behavioral studies can, therefore, provide a valuable integrative link between physiological and ecological effects. Despite the advantages of behavioral analysis development of behavioral toxicity, biotests is greatly hampered by the lack of dedicated laboratory automation, in particular, user-friendly and automated video microscopy systems. In this work we present a proof-of-concept development of an optical system capable of tracking embryonic vertebrates behavioral responses using automated and vastly miniaturized time-resolved video-microscopy. We have employed miniaturized CMOS cameras to perform high definition video recording and analysis of earliest vertebrate behavioral responses. The main objective was to develop a biocompatible embryo positioning structures that were suitable for high-throughput imaging as well as video capture and video analysis algorithms. This system should support the development of sub-lethal and behavioral markers for accelerated environmental monitoring.

Interpretation of physiological indicators of motivation: Caveats and recommendations.

PubMed

Richter, Michael; Slade, Kate

2017-09-01

Motivation scientists employing physiological measures to gather information about motivation-related states are at risk of committing two fundamental errors: overstating the inferences that can be drawn from their physiological measures and circular reasoning. We critically discuss two complementary approaches, Cacioppo and colleagues' model of psychophysiological relations and construct validation theory, to highlight the conditions under which these errors are committed and provide guidance on how to avoid them. In particular, we demonstrate that the direct inference from changes in a physiological measure to changes in a motivation-related state requires the demonstration that the measure is not related to other relevant psychological states. We also point out that circular reasoning can be avoided by separating the definition of the motivation-related state from the hypotheses that are empirically tested. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of Clinically Relevant Implantable Pressure Sensors: Perspectives and Challenges

PubMed Central

Clausen, Ingelin; Glott, Thomas

2014-01-01

This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS) technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians. Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported. PMID:25248071

Development of clinically relevant implantable pressure sensors: perspectives and challenges.

PubMed

Clausen, Ingelin; Glott, Thomas

2014-09-22

This review describes different aspects to consider when developing implantable pressure sensor systems. Measurement of pressure is in general highly important in clinical practice and medical research. Due to the small size, light weight and low energy consumption Micro Electro Mechanical Systems (MEMS) technology represents new possibilities for monitoring of physiological parameters inside the human body. Development of clinical relevant sensors requires close collaboration between technological experts and medical clinicians.  Site of operation, size restrictions, patient safety, and required measurement range and resolution, are only some conditions that must be taken into account. An implantable device has to operate under very hostile conditions. Long-term in vivo pressure measurements are particularly demanding because the pressure sensitive part of the sensor must be in direct or indirect physical contact with the medium for which we want to detect the pressure. New sensor packaging concepts are demanded and must be developed through combined effort between scientists in MEMS technology, material science, and biology. Before launching a new medical device on the market, clinical studies must be performed. Regulatory documents and international standards set the premises for how such studies shall be conducted and reported.

Bart's familiar quotations: the enduring biological wisdom of George A. Bartholomew.

PubMed

Huey, Raymond B; Bennett, Albert F

2008-01-01

George A. Bartholomew was one of the most influential organismal biologists of the twentieth century. His insights and research were fundamental to the establishment and growth of physiological ecology and evolutionary physiology. In the process of fostering that area of science, he created a body of literature that is striking in the clarity of its thought and presentation. Here we present some of his most insightful and important quotations, group them thematically, and comment on their original context and their continuing relevance.

A conceptual framework for homeostasis: development and validation

PubMed Central

Wenderoth, Mary Pat; Michael, Joel; Cliff, William; Wright, Ann; Modell, Harold

2016-01-01

We have developed and validated a conceptual framework for understanding and teaching organismal homeostasis at the undergraduate level. The resulting homeostasis conceptual framework details critical components and constituent ideas underlying the concept of homeostasis. It has been validated by a broad range of physiology faculty members from community colleges, primarily undergraduate institutions, research universities, and medical schools. In online surveys, faculty members confirmed the relevance of each item in the framework for undergraduate physiology and rated the importance and difficulty of each. The homeostasis conceptual framework was constructed as a guide for teaching and learning of this critical core concept in physiology, and it also paves the way for the development of a concept inventory for homeostasis. PMID:27105740

Physiologically Relevant Changes in Serotonin Resolved by Fast Microdialysis

PubMed Central

2013-01-01

Online microdialysis is a sampling and detection method that enables continuous interrogation of extracellular molecules in freely moving subjects under behaviorally relevant conditions. A majority of recent publications using brain microdialysis in rodents report sample collection times of 20–30 min. These long sampling times are due, in part, to limitations in the detection sensitivity of high performance liquid chromatography (HPLC). By optimizing separation and detection conditions, we decreased the retention time of serotonin to 2.5 min and the detection threshold to 0.8 fmol. Sampling times were consequently reduced from 20 to 3 min per sample for online detection of serotonin (and dopamine) in brain dialysates using a commercial HPLC system. We developed a strategy to collect and to analyze dialysate samples continuously from two animals in tandem using the same instrument. Improvements in temporal resolution enabled elucidation of rapid changes in extracellular serotonin levels associated with mild stress and circadian rhythms. These dynamics would be difficult or impossible to differentiate using conventional microdialysis sampling rates. PMID:23614776

Maintenance of neural progenitor cell stemness in 3D hydrogels requires matrix remodelling

NASA Astrophysics Data System (ADS)

Madl, Christopher M.; Lesavage, Bauer L.; Dewi, Ruby E.; Dinh, Cong B.; Stowers, Ryan S.; Khariton, Margarita; Lampe, Kyle J.; Nguyen, Duong; Chaudhuri, Ovijit; Enejder, Annika; Heilshorn, Sarah C.

2017-12-01

Neural progenitor cell (NPC) culture within three-dimensional (3D) hydrogels is an attractive strategy for expanding a therapeutically relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically relevant range of stiffness from ~0.5 to 50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodelling to facilitate cadherin-mediated cell-cell contact and promote β-catenin signalling. In two additional hydrogel systems, permitting NPC-mediated matrix remodelling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodelling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D.

Maintenance of Neural Progenitor Cell Stemness in 3D Hydrogels Requires Matrix Remodeling

PubMed Central

Madl, Christopher M.; LeSavage, Bauer L.; Dewi, Ruby E.; Dinh, Cong B.; Stowers, Ryan S.; Khariton, Margarita; Lampe, Kyle J.; Nguyen, Duong; Chaudhuri, Ovijit; Enejder, Annika; Heilshorn, Sarah C.

2017-01-01

Neural progenitor cell (NPC) culture within 3D hydrogels is an attractive strategy for expanding a therapeutically-relevant number of stem cells. However, relatively little is known about how 3D material properties such as stiffness and degradability affect the maintenance of NPC stemness in the absence of differentiation factors. Over a physiologically-relevant range of stiffness from ~0.5–50 kPa, stemness maintenance did not correlate with initial hydrogel stiffness. In contrast, hydrogel degradation was both correlated with, and necessary for, maintenance of NPC stemness. This requirement for degradation was independent of cytoskeletal tension generation and presentation of engineered adhesive ligands, instead relying on matrix remodeling to facilitate cadherin-mediated cell-cell contact and promote β-catenin signaling. In two additional hydrogel systems, permitting NPC-mediated matrix remodeling proved to be a generalizable strategy for stemness maintenance in 3D. Our findings have identified matrix remodeling, in the absence of cytoskeletal tension generation, as a previously unknown strategy to maintain stemness in 3D. PMID:29115291

Joint Feature Extraction and Classifier Design for ECG-Based Biometric Recognition.

PubMed

Gutta, Sandeep; Cheng, Qi

2016-03-01

Traditional biometric recognition systems often utilize physiological traits such as fingerprint, face, iris, etc. Recent years have seen a growing interest in electrocardiogram (ECG)-based biometric recognition techniques, especially in the field of clinical medicine. In existing ECG-based biometric recognition methods, feature extraction and classifier design are usually performed separately. In this paper, a multitask learning approach is proposed, in which feature extraction and classifier design are carried out simultaneously. Weights are assigned to the features within the kernel of each task. We decompose the matrix consisting of all the feature weights into sparse and low-rank components. The sparse component determines the features that are relevant to identify each individual, and the low-rank component determines the common feature subspace that is relevant to identify all the subjects. A fast optimization algorithm is developed, which requires only the first-order information. The performance of the proposed approach is demonstrated through experiments using the MIT-BIH Normal Sinus Rhythm database.

The Intracrine Renin-Angiotensin System

PubMed Central

Kumar, Rajesh; Thomas, Candice M.; Yong, Qian Chen; Chen, Wen; Baker, Kenneth M.

2014-01-01

The renin-angiotensin system (RAS) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The major bioactive peptide of the system, angiotensin (Ang) II, is neither synthesized in, nor targets one specific organ. New research has identified additional peptides with important physiological and pathological roles. More peptides also mean newer enzymatic cascades that generate these peptides and more receptors that mediate the function. In addition, completely different roles of components that constitute the RAS have been uncovered, such as that for prorenin via the prorenin receptor. Complexity of the RAS is further enhanced by the presence of sub-systems in tissues, which act in an autocrine/paracrine manner independent of the endocrine system. The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels. The intracellular RAS is a relatively new concept for the RAS. The current review presents a synopsis of the literature on this system in different tissues. PMID:22590974

Computational model of cerebral blood flow redistribution during cortical spreading depression

NASA Astrophysics Data System (ADS)

Verisokin, Andrey Y.; Verveyko, Darya V.; Postnov, Dmitry E.

2016-04-01

In recent decades modelling studies on cortical spreading depression (CSD) and migraine waves successfully contributed to formation of modern view on these fundamental phenomena of brain physiology. However, due to the extreme complexity of object under study (brain cortex) and the diversity of involved physiological pathways, the development of new mathematical models of CSD is still a very relevant and challenging research problem. In our study we follow the functional modelling approach aimed to map the action of known physiological pathways to the specific nonlinear mechanisms that govern formation and evolution of CSD wave patterns. Specifically, we address the role of cerebral blood flow (CBF) redistribution that is caused by excessive neuronal activity by means of neurovascular coupling and mediates a spatial pattern of oxygen and glucose delivery. This in turn changes the local metabolic status of neural tissue. To build the model we simplify the web of known cell-to-cell interactions within a neurovascular unit by selecting the most relevant ones, such as local neuron-induced elevation of extracellular potassium concentration and biphasic response of arteriole radius. We propose the lumped description of distance-dependent hemodynamic coupling that fits the most recent experimental findings.

Tunable Collagen I Hydrogels for Engineered Physiological Tissue Micro-Environments

PubMed Central

Antoine, Elizabeth E.; Vlachos, Pavlos P.; Rylander, Marissa N.

2015-01-01

Collagen I hydrogels are commonly used to mimic the extracellular matrix (ECM) for tissue engineering applications. However, the ability to design collagen I hydrogels similar to the properties of physiological tissues has been elusive. This is primarily due to the lack of quantitative correlations between multiple fabrication parameters and resulting material properties. This study aims to enable informed design and fabrication of collagen hydrogels in order to reliably and reproducibly mimic a variety of soft tissues. We developed empirical predictive models relating fabrication parameters with material and transport properties. These models were obtained through extensive experimental characterization of these properties, which include compression modulus, pore and fiber diameter, and diffusivity. Fabrication parameters were varied within biologically relevant ranges and included collagen concentration, polymerization pH, and polymerization temperature. The data obtained from this study elucidates previously unknown fabrication-property relationships, while the resulting equations facilitate informed a priori design of collagen hydrogels with prescribed properties. By enabling hydrogel fabrication by design, this study has the potential to greatly enhance the utility and relevance of collagen hydrogels in order to develop physiological tissue microenvironments for a wide range of tissue engineering applications. PMID:25822731

Blunt trauma and operative care in microgravity: a review of microgravity physiology and surgical investigations with implications for critical care and operative treatment in space.

PubMed

Kirkpatrick, A W; Campbell, M R; Novinkov, O L; Goncharov, I B; Kovachevich, I V

1997-05-01

The assembly of the International Space Station in a low earth orbit will soon become a reality. The National Aeronautics and Space Administration envisions inhabited lunar bases and staffed missions to Mars in the future. Increasing numbers of astronauts, construction of high-mass structures, increased extra-vehicular activity, and prolonged if not prohibitive medical evacuation times to earth underscore the need to address requirements for trauma care in nonterrestrial environments. A search was carried out to review the relevant literature in the MEDLINE and SPACELINE databases. All related Technical, Corporate, and Flight Test Reports in the KRUG Life Sciences corporate library were also reviewed. Bibliographies of all articles were then reviewed from these papers to identify additional pertinent literature. Senior Russian investigators reviewed the Russian literature and translated Russian publications when appropriate. Personal communication and discussion with active microgravity investigators and ongoing microgravity research supplemented published reports. A large volume of data exist to document the multiple detrimental physiologic effects of microgravity exposure on human physiology. Organs systems such as cardiovascular, neurohumoral, immune, hematopoetic, and musculoskeletal systems may be particularly affected. These physiologic changes suggest an impaired ability to withstand major systemic trauma. Observational data also suggest adverse changes in numerous aspects of response to wounding and injury, and in areas such as the behavior of hemorrhage, microbiologic flora, and wound healing. In addition to an increased volume of ongoing and anticipated basic science research in microgravity physiology, preliminary studies of clinical diagnosis and therapy have been carried out in microgravity and microgravity laboratories. The feasibility of a wide range of ancillary critical care techniques has been verified in the parabolic flight model of microgravity. Although Russian investigators first performed laparotomies on rabbits in parabolic flight in 1967, only recently have American investigators demonstrated the reproducible feasibility of open and endoscopic surgical procedures under general anesthetic in animal models in a microgravity environment. With appropriate instrumentation and personnel, the majority of resuscitative and surgical interventions required to stabilize a severely injured astronaut are feasible in a microgravity environment. Onboard limitations in mass, volume, and power that are ever present in any spacecraft design will limit the realistic capabilities of the medical system. Standard proved and tested trauma and operative management protocols will constitute the basis for extra-terrestrial care. Surgeons should familiarize themselves with the microgravity environment and remain active in planning trauma care for the continued exploration of space.

Targeting innate immunity for neurodegenerative disorders of the central nervous system.

PubMed

Andreasson, Katrin I; Bachstetter, Adam D; Colonna, Marco; Ginhoux, Florent; Holmes, Clive; Lamb, Bruce; Landreth, Gary; Lee, Daniel C; Low, Donovan; Lynch, Marina A; Monsonego, Alon; O'Banion, M Kerry; Pekny, Milos; Puschmann, Till; Russek-Blum, Niva; Sandusky, Leslie A; Selenica, Maj-Linda B; Takata, Kazuyuki; Teeling, Jessica; Town, Terrence; Van Eldik, Linda J

2016-09-01

Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. © 2016 International Society for Neurochemistry.

Faculty perceptions of the strengths, weaknesses and future prospects of the current medical undergraduate experimental physiology curriculum in Gujarat, India.

PubMed

Paralikar, Swapnil; Shah, Chinmay

2015-01-01

Over the past several years, an opinion has emerged in India that the current practical curricula in medical schools fail to meet many of the objectives for which they were instituted. Hence, this study has assessed the perception of physiology faculty members regarding the current experimental physiology curriculum in one Indian state, Gujarat. The faculty were of the opinion that many of the topics currently taught in experimental physiology (amphibian nerve-muscle and heart muscle experiments) were outdated and clinically irrelevant: Therefore, the faculty advocated that duration of teaching time devoted to some of these topics should be reduced and topics with clinical relevance should be introduced at the undergraduate level. The faculty also felt that more emphasis should be laid on highlighting the clinical aspect related to each concept taught in experimental physiology . Moreover, a majority of faculty members were in favour of replacing the current practice in Gujarat of teaching experimental physiology only by explanation of graphs obtained from experiments conducted in the previous years, with computer assisted learning in small groups.

A Method of High Throughput Monitoring Crop Physiology Using Chlorophyll Fluorescence and Multispectral Imaging.

PubMed

Wang, Heng; Qian, Xiangjie; Zhang, Lan; Xu, Sailong; Li, Haifeng; Xia, Xiaojian; Dai, Liankui; Xu, Liang; Yu, Jingquan; Liu, Xu

2018-01-01

We present a high throughput crop physiology condition monitoring system and corresponding monitoring method. The monitoring system can perform large-area chlorophyll fluorescence imaging and multispectral imaging. The monitoring method can determine the crop current condition continuously and non-destructively. We choose chlorophyll fluorescence parameters and relative reflectance of multispectral as the indicators of crop physiological status. Using tomato as experiment subject, the typical crop physiological stress, such as drought, nutrition deficiency and plant disease can be distinguished by the monitoring method. Furthermore, we have studied the correlation between the physiological indicators and the degree of stress. Besides realizing the continuous monitoring of crop physiology, the monitoring system and method provide the possibility of machine automatic diagnosis of the plant physiology. Highlights: A newly designed high throughput crop physiology monitoring system and the corresponding monitoring method are described in this study. Different types of stress can induce distinct fluorescence and spectral characteristics, which can be used to evaluate the physiological status of plants.

Non-invasive cortisol measurements as indicators of physiological stress responses in guinea pigs

PubMed Central

Pschernig, Elisabeth; Wallner, Bernard; Millesi, Eva

2016-01-01

Non-invasive measurements of glucocorticoid (GC) concentrations, including cortisol and corticosterone, serve as reliable indicators of adrenocortical activities and physiological stress loads in a variety of species. As an alternative to invasive analyses based on plasma, GC concentrations in saliva still represent single-point-of-time measurements, suitable for studying short-term or acute stress responses, whereas fecal GC metabolites (FGMs) reflect overall stress loads and stress responses after a species-specific time frame in the long-term. In our study species, the domestic guinea pig, GC measurements are commonly used to indicate stress responses to different environmental conditions, but the biological relevance of non-invasive measurements is widely unknown. We therefore established an experimental protocol based on the animals’ natural stress responses to different environmental conditions and compared GC levels in plasma, saliva, and fecal samples during non-stressful social isolations and stressful two-hour social confrontations with unfamiliar individuals. Plasma and saliva cortisol concentrations were significantly increased directly after the social confrontations, and plasma and saliva cortisol levels were strongly correlated. This demonstrates a high biological relevance of GC measurements in saliva. FGM levels measured 20 h afterwards, representing the reported mean gut passage time based on physiological validations, revealed that the overall stress load was not affected by the confrontations, but also no relations to plasma cortisol levels were detected. We therefore measured FGMs in two-hour intervals for 24 h after another social confrontation and detected significantly increased levels after four to twelve hours, reaching peak concentrations already after six hours. Our findings confirm that non-invasive GC measurements in guinea pigs are highly biologically relevant in indicating physiological stress responses compared to circulating levels in plasma in the short- and long-term. Our approach also underlines the importance of detailed investigations on how to use and interpret non-invasive measurements, including the determination of appropriate time points for sample collections. PMID:26839750

Placenta-on-a-chip: a novel platform to study the biology of the human placenta.

PubMed

Lee, Ji Soo; Romero, Roberto; Han, Yu Mi; Kim, Hee Chan; Kim, Chong Jai; Hong, Joon-Seok; Huh, Dongeun

2016-01-01

Studying the biology of the human placenta represents a major experimental challenge. Although conventional cell culture techniques have been used to study different types of placenta-derived cells, current in vitro models have limitations in recapitulating organ-specific structure and key physiological functions of the placenta. Here we demonstrate that it is possible to leverage microfluidic and microfabrication technologies to develop a microengineered biomimetic model that replicates the architecture and function of the placenta. A "Placenta-on-a-Chip" microdevice was created by using a set of soft elastomer-based microfabrication techniques known as soft lithography. This microsystem consisted of two polydimethylsiloxane (PDMS) microfluidic channels separated by a thin extracellular matrix (ECM) membrane. To reproduce the placental barrier in this model, human trophoblasts (JEG-3) and human umbilical vein endothelial cells (HUVECs) were seeded onto the opposite sides of the ECM membrane and cultured under dynamic flow conditions to form confluent epithelial and endothelial layers in close apposition. We tested the physiological function of the microengineered placental barrier by measuring glucose transport across the trophoblast-endothelial interface over time. The permeability of the barrier study was analyzed and compared to that obtained from acellular devices and additional control groups that contained epithelial or endothelial layers alone. Our microfluidic cell culture system provided a tightly controlled fluidic environment conducive to the proliferation and maintenance of JEG-3 trophoblasts and HUVECs on the ECM scaffold. Prolonged culture in this model produced confluent cellular monolayers on the intervening membrane that together formed the placental barrier. This in vivo-like microarchitecture was also critical for creating a physiologically relevant effective barrier to glucose transport. Quantitative investigation of barrier function was conducted by calculating permeability coefficients and metabolic rates in varying conditions of barrier structure. The rates of glucose transport and metabolism were consistent with previously reported in vivo observations. The "Placenta-on-a-Chip" microdevice described herein provides new opportunities to simulate and analyze critical physiological responses of the placental barrier. This system may be used to address the major limitations of existing placenta model systems and serve to enable research platforms for reproductive biology and medicine.

A physical action potential generator: design, implementation and evaluation.

PubMed

Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

2015-01-01

The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

Conservation physiology in practice: how physiological knowledge has improved our ability to sustainably manage Pacific salmon during up-river migration.

PubMed

Cooke, Steven J; Hinch, Scott G; Donaldson, Michael R; Clark, Timothy D; Eliason, Erika J; Crossin, Glenn T; Raby, Graham D; Jeffries, Ken M; Lapointe, Mike; Miller, Kristi; Patterson, David A; Farrell, Anthony P

2012-06-19

Despite growing interest in conservation physiology, practical examples of how physiology has helped to understand or to solve conservation problems remain scarce. Over the past decade, an interdisciplinary research team has used a conservation physiology approach to address topical conservation concerns for Pacific salmon. Here, we review how novel applications of tools such as physiological telemetry, functional genomics and laboratory experiments on cardiorespiratory physiology have shed light on the effect of fisheries capture and release, disease and individual condition, and stock-specific consequences of warming river temperatures, respectively, and discuss how these findings have or have not benefited Pacific salmon management. Overall, physiological tools have provided remarkable insights into the effects of fisheries capture and have helped to enhance techniques for facilitating recovery from fisheries capture. Stock-specific cardiorespiratory thresholds for thermal tolerances have been identified for sockeye salmon and can be used by managers to better predict migration success, representing a rare example that links a physiological scope to fitness in the wild population. Functional genomics approaches have identified physiological signatures predictive of individual migration mortality. Although fisheries managers are primarily concerned with population-level processes, understanding the causes of en route mortality provides a mechanistic explanation and can be used to refine management models. We discuss the challenges that we have overcome, as well as those that we continue to face, in making conservation physiology relevant to managers of Pacific salmon.

Conservation physiology in practice: how physiological knowledge has improved our ability to sustainably manage Pacific salmon during up-river migration

PubMed Central

Cooke, Steven J.; Hinch, Scott G.; Donaldson, Michael R.; Clark, Timothy D.; Eliason, Erika J.; Crossin, Glenn T.; Raby, Graham D.; Jeffries, Ken M.; Lapointe, Mike; Miller, Kristi; Patterson, David A.; Farrell, Anthony P.

2012-01-01

Despite growing interest in conservation physiology, practical examples of how physiology has helped to understand or to solve conservation problems remain scarce. Over the past decade, an interdisciplinary research team has used a conservation physiology approach to address topical conservation concerns for Pacific salmon. Here, we review how novel applications of tools such as physiological telemetry, functional genomics and laboratory experiments on cardiorespiratory physiology have shed light on the effect of fisheries capture and release, disease and individual condition, and stock-specific consequences of warming river temperatures, respectively, and discuss how these findings have or have not benefited Pacific salmon management. Overall, physiological tools have provided remarkable insights into the effects of fisheries capture and have helped to enhance techniques for facilitating recovery from fisheries capture. Stock-specific cardiorespiratory thresholds for thermal tolerances have been identified for sockeye salmon and can be used by managers to better predict migration success, representing a rare example that links a physiological scope to fitness in the wild population. Functional genomics approaches have identified physiological signatures predictive of individual migration mortality. Although fisheries managers are primarily concerned with population-level processes, understanding the causes of en route mortality provides a mechanistic explanation and can be used to refine management models. We discuss the challenges that we have overcome, as well as those that we continue to face, in making conservation physiology relevant to managers of Pacific salmon. PMID:22566681

Mesenchymal Stem Cells for Osteochondral Tissue Engineering

PubMed Central

Ng, Johnathan; Bernhard, Jonathan; Vunjak-Novakovic, Gordana

2017-01-01

Summary Mesenchymal stem cells (MSC) are of major interest to regenerative medicine, because of the ease of harvesting from a variety of sources (including bone marrow and fat aspirates) and ability to form a range of mesenchymal tissues, in vitro and in vivo. We focus here on the use of MSCs for engineering of cartilage, bone, and complex osteochondral tissue constructs, using protocols that replicate some aspects of the natural mesodermal development. For engineering of human bone, we discuss some of the current advances, and highlight the use of perfusion bioreactors for supporting anatomically exact human bone grafts. For engineering of human cartilage, we discuss limitations of current approaches, and highlight engineering of stratified, mechanically functional human cartilage interfaced with bone by mesenchymal condensation of MSCs. Taken together, the current advances enable engineering physiologically relevant bone, cartilage and osteochondral composites, and physiologically relevant studies of osteochondral development and disease. PMID:27236665

Magnetic Resonance Imaging of Electrolysis.

PubMed Central

Meir, Arie; Hjouj, Mohammad; Rubinsky, Liel; Rubinsky, Boris

2015-01-01

This study explores the hypothesis that Magnetic Resonance Imaging (MRI) can image the process of electrolysis by detecting pH fronts. The study has relevance to real time control of cell ablation with electrolysis. To investigate the hypothesis we compare the following MR imaging sequences: T1 weighted, T2 weighted and Proton Density (PD), with optical images acquired using pH-sensitive dyes embedded in a physiological saline agar solution phantom treated with electrolysis and discrete measurements with a pH microprobe. We further demonstrate the biological relevance of our work using a bacterial E. Coli model, grown on the phantom. The results demonstrate the ability of MRI to image electrolysis produced pH changes in a physiological saline phantom and show that these changes correlate with cell death in the E. Coli model grown on the phantom. The results are promising and invite further experimental research. PMID:25659942

MicroRNAs and the metabolic hallmarks of aging.

PubMed

Victoria, Berta; Nunez Lopez, Yury O; Masternak, Michal M

2017-11-05

Aging, the natural process of growing older, is characterized by a progressive deterioration of physiological homeostasis at the cellular, tissue, and organismal level. Metabolically, the aging process is characterized by extensive changes in body composition, multi-tissue/multi-organ insulin resistance, and physiological declines in multiple signaling pathways including growth hormone, insulin/insulin-like growth factor 1, and sex steroids regulation. With this review, we intend to consolidate published information about microRNAs that regulate critical metabolic processes relevant to aging. In certain occasions we uncover relationships likely relevant to aging, which has not been directly described before, such as the miR-451/AMPK axis. We have also included a provocative section highlighting the potential role in aging of a new designation of miRNAs, namely fecal miRNAs, recently discovered to regulate intestinal microbiota in mammals. Copyright © 2016. Published by Elsevier B.V.

Mammalian lipoxygenases and their biological relevance

PubMed Central

Kuhn, Hartmut; Banthiya, Swathi; van Leyen, Klaus

2015-01-01

Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders. PMID:25316652

The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

PubMed

Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L

2017-05-01

The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and demonstrate supersaturation and precipitation of dipyridamole and ketoconazole. We therefore conclude that the GIS has been shown to be a good biopredictive tool to predict in vivo bioperformance of BCS class IIb drugs that can be used to optimize oral formulations. Copyright © 2017. Published by Elsevier B.V.

A Waveform Archiving System for the GE Solar 8000i Bedside Monitor.

PubMed

Fanelli, Andrea; Jaishankar, Rohan; Filippidis, Aristotelis; Holsapple, James; Heldt, Thomas

2018-01-01

Our objective was to develop, deploy, and test a data-acquisition system for the reliable and robust archiving of high-resolution physiological waveform data from a variety of bedside monitoring devices, including the GE Solar 8000i patient monitor, and for the logging of ancillary clinical and demographic information. The data-acquisition system consists of a computer-based archiving unit and a GE Tram Rac 4A that connects to the GE Solar 8000i monitor. Standard physiological front-end sensors connect directly to the Tram Rac, which serves as a port replicator for the GE monitor and provides access to these waveform signals through an analog data interface. Together with the GE monitoring data streams, we simultaneously collect the cerebral blood flow velocity envelope from a transcranial Doppler ultrasound system and a non-invasive arterial blood pressure waveform along a common time axis. All waveform signals are digitized and archived through a LabView-controlled interface that also allows for the logging of relevant meta-data such as clinical and patient demographic information. The acquisition system was certified for hospital use by the clinical engineering team at Boston Medical Center, Boston, MA, USA. Over a 12-month period, we collected 57 datasets from 11 neuro-ICU patients. The system provided reliable and failure-free waveform archiving. We measured an average temporal drift between waveforms from different monitoring devices of 1 ms every 66 min of recorded data. The waveform acquisition system allows for robust real-time data acquisition, processing, and archiving of waveforms. The temporal drift between waveforms archived from different devices is entirely negligible, even for long-term recording.

Establishment of a cell-based wound healing assay for bio-relevant testing of wound therapeutics.

PubMed

Planz, Viktoria; Wang, Jing; Windbergs, Maike

Predictive in vitro testing of novel wound therapeutics requires adequate cell-based bio-assays. Such assays represent an integral part during preclinical development as pre-step before entering in vivo studies. Simple "scratch tests" based on defected skin cell monolayers exist, however these can solely be used for testing liquids, as cell monolayer destruction and excessive hydration limit their applicability for (semi-)solid systems like wound dressings. In this context, a cell-based wound healing assay is introduced for rapid and predictive testing of wound therapeutics independent of their physical state in a bio-relevant environment. A novel wound healing assay was established for bio-relevant and predictive testing of (semi-) solid wound therapeutics. The assay allows for physiologically relevant hydration of the tested wound therapeutics at the air-liquid interface and their removal without cell monolayer disruption. In a proof-of-concept study, the applicability and discriminative power could be demonstrated by examining unloaded and drug-loaded wound dressings with two different established wound healing actives (dexpanthenol and metyrapone) and their effect on skin cell behavior. The influence of the released drug on the cells´ healing behavior could successfully be monitored over time. Wound size assessment after 96h resulted in an eight fold smaller wound area for drug treated models compared to the ones treated with unloaded fibers and non-treated wounds. This assay provides valuable first insights towards the establishment of a valid screening and evaluation tool for preclinical wound therapeutic development from liquid to (semi-)solid systems to improve predictability in a simple, yet standardized way. Copyright © 2017 Elsevier Inc. All rights reserved.

The physiological equivalent temperature - a universal index for the biometeorological assessment of the thermal environment

NASA Astrophysics Data System (ADS)

Höppe, P.

With considerably increased coverage of weather information in the news media in recent years in many countries, there is also more demand for data that are applicable and useful for everyday life. Both the perception of the thermal component of weather as well as the appropriate clothing for thermal comfort result from the integral effects of all meteorological parameters relevant for heat exchange between the body and its environment. Regulatory physiological processes can affect the relative importance of meteorological parameters, e.g. wind velocity becomes more important when the body is sweating. In order to take into account all these factors, it is necessary to use a heat-balance model of the human body. The physiological equivalent temperature (PET) is based on the Munich Energy-balance Model for Individuals (MEMI), which models the thermal conditions of the human body in a physiologically relevant way. PET is defined as the air temperature at which, in a typical indoor setting (without wind and solar radiation), the heat budget of the human body is balanced with the same core and skin temperature as under the complex outdoor conditions to be assessed. This way PET enables a layperson to compare the integral effects of complex thermal conditions outside with his or her own experience indoors. On hot summer days, for example, with direct solar irradiation the PET value may be more than 20 K higher than the air temperature, on a windy day in winter up to 15 K lower.

Selecting boundary conditions in physiological strain analysis of the femur: Balanced loads, inertia relief method and follower load.

PubMed

Heyland, Mark; Trepczynski, Adam; Duda, Georg N; Zehn, Manfred; Schaser, Klaus-Dieter; Märdian, Sven

2015-12-01

Selection of boundary constraints may influence amount and distribution of loads. The purpose of this study is to analyze the potential of inertia relief and follower load to maintain the effects of musculoskeletal loads even under large deflections in patient specific finite element models of intact or fractured bone compared to empiric boundary constraints which have been shown to lead to physiological displacements and surface strains. The goal is to elucidate the use of boundary conditions in strain analyses of bones. Finite element models of the intact femur and a model of clinically relevant fracture stabilization by locking plate fixation were analyzed with normal walking loading conditions for different boundary conditions, specifically re-balanced loading, inertia relief and follower load. Peak principal cortex surface strains for different boundary conditions are consistent (maximum deviation 13.7%) except for inertia relief without force balancing (maximum deviation 108.4%). Influence of follower load on displacements increases with higher deflection in fracture model (from 3% to 7% for force balanced model). For load balanced models, follower load had only minor influence, though the effect increases strongly with higher deflection. Conventional constraints of fixed nodes in space should be carefully reconsidered because their type and position are challenging to justify and for their potential to introduce relevant non-physiological reaction forces. Inertia relief provides an alternative method which yields physiological strain results. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Understanding Kidney Disease: Toward the Integration of Regulatory Networks Across Species

PubMed Central

Ju, Wenjun; Brosius, Frank C.

2010-01-01

Animal models have long been useful in investigating both normal and abnormal human physiology. Systems biology provides a relatively new set of approaches to identify similarities and differences between animal models and humans that may lead to a more comprehensive understanding of human kidney pathophysiology. In this review, we briefly describe how genome-wide analyses of mouse models have helped elucidate features of human kidney diseases, discuss strategies to achieve effective network integration, and summarize currently available web-based tools that may facilitate integration of data across species. The rapid progress in systems biology and orthology, as well as the advent of web-based tools to facilitate these processes, now make it possible to take advantage of knowledge from distant animal species in targeted identification of regulatory networks that may have clinical relevance for human kidney diseases. PMID:21044762

PROBLEMS OF CYBERNETICS AND SPACE MEDICINE (in Russian)

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

Parin, V.V.; Baevskii, R.M.

1963-01-01

Problems of cybernetics are discussed with reference to space medicine. The information theory is widely used for solving the problems relevant to radiotelemetric transmission of biological data. Construction of devices for automatic medical control of the condition of the crew of the space ship has a direct bearing to electron diagnostic machines. Mathematical methods and the computing technic are used for analyzing experimental evidence. The theory of automatic regulation was applied for modeling physiological reactions, for developing closed ecological systems, and for solving the problems of driving space ships. The problems bearing on the modifications undergone by the information inmore » the brain are of primary importance for the study of the effect of the space flight conditions upon the efficiency of man, the activity of his nervous system and of his analyzers. (P.C.H.)« less

Pain in rheumatic diseases: how relevant is it?

PubMed

Sarzi-Puttini, P; Atzeni, F; Salaffi, F

2014-06-06

Pain, a complex phenomenon influenced by a series of genetic, biological, psychological and social factors, is a major component of many rheumatological conditions and the result of physiological interactions between central and peripheral nervous system signalling. It may be acute or chronic (generally defined as lasting ≥ three months): acute pain is often primarily attributable to inflammation and/or damage to peripheral structures (i.e. nociceptive input), whereas chronic pain is more likely to be due to input from the central nervous system (CNS). The many different aspects of pain mean that rheumatologists and other clinicians need to have enough expertise to diagnose the type of pain correctly and treat it appropriately. However, most rheumatologists receive little formal training concerning contemporary theories of pain processing or management, and this may affect the clinical results of any specific target therapy.

Allometric scaling in-vitro

NASA Astrophysics Data System (ADS)

Ahluwalia, Arti

2017-02-01

About two decades ago, West and coworkers established a model which predicts that metabolic rate follows a three quarter power relationship with the mass of an organism, based on the premise that tissues are supplied nutrients through a fractal distribution network. Quarter power scaling is widely considered a universal law of biology and it is generally accepted that were in-vitro cultures to obey allometric metabolic scaling, they would have more predictive potential and could, for instance, provide a viable substitute for animals in research. This paper outlines a theoretical and computational framework for establishing quarter power scaling in three-dimensional spherical constructs in-vitro, starting where fractal distribution ends. Allometric scaling in non-vascular spherical tissue constructs was assessed using models of Michaelis Menten oxygen consumption and diffusion. The models demonstrate that physiological scaling is maintained when about 5 to 60% of the construct is exposed to oxygen concentrations less than the Michaelis Menten constant, with a significant concentration gradient in the sphere. The results have important implications for the design of downscaled in-vitro systems with physiological relevance.

Signaling, physiological functions and clinical relevance of the G protein-coupled estrogen receptor GPER.

PubMed

Prossnitz, Eric R; Barton, Matthias

2009-09-01

GPR30, now named GPER1 (G protein-coupled estrogen receptor1) or GPER here, was first identified as an orphan 7-transmembrane G protein-coupled receptor by multiple laboratories using either homology cloning or differential expression and subsequently shown to be required for estrogen-mediated signaling in certain cancer cells. The actions of estrogen are extensive in the body and are thought to be mediated predominantly by classical nuclear estrogen receptors that act as transcription factors/regulators. Nevertheless, certain aspects of estrogen function remain incompatible with the generally accepted mechanisms of classical estrogen receptor action. Many recent studies have revealed that GPER contributes to some of the actions of estrogen, including rapid signaling events and rapid transcriptional activation. With the introduction of GPER-selective ligands and GPER knockout mice, the functions of GPER are becoming more clearly defined. In many cases, there appears to be a complex interplay between the two receptor systems, suggesting that estrogen-mediated physiological responses may be mediated by either receptor or a combination of both receptor types, with important medical implications.

What the Toadfish Ear Tells the Toadfish Brain About Sound.

PubMed

Edds-Walton, Peggy L

2016-01-01

Of the three, paired otolithic endorgans in the ear of teleost fishes, the saccule is the one most often demonstrated to have a major role in encoding frequencies of biologically relevant sounds. The toadfish saccule also encodes sound level and sound source direction in the phase-locked activity conveyed via auditory afferents to nuclei of the ipsilateral octaval column in the medulla. Although paired auditory receptors are present in teleost fishes, binaural processes were believed to be unimportant due to the speed of sound in water and the acoustic transparency of the tissues in water. In contrast, there are behavioral and anatomical data that support binaural processing in fishes. Studies in the toadfish combined anatomical tract-tracing and physiological recordings from identified sites along the ascending auditory pathway to document response characteristics at each level. Binaural computations in the medulla and midbrain sharpen the directional information provided by the saccule. Furthermore, physiological studies in the central nervous system indicated that encoding frequency, sound level, temporal pattern, and sound source direction are important components of what the toadfish ear tells the toadfish brain about sound.

Does selection for short sleep duration explain human vulnerability to Alzheimer's disease?

PubMed

Nesse, Randolph M; Finch, Caleb E; Nunn, Charles L

2017-01-16

Compared with other primates, humans sleep less and have a much higher prevalence of Alzheimer 's disease (AD) pathology. This article reviews evidence relevant to the hypothesis that natural selection for shorter sleep time in humans has compromised the efficacy of physiological mechanisms that protect against AD during sleep. In particular, the glymphatic system drains interstitial fluid from the brain, removing extra-cellular amyloid beta (eAβ) twice as fast during sleep. In addition, melatonin - a peptide hormone that increases markedly during sleep - is an effective antioxidant that inhibits the polymerization of soluble eAβ into insoluble amyloid fibrils that are associated with AD. Sleep deprivation increases plaque formation and AD, which itself disrupts sleep, potentially creating a positive feedback cycle. These and other physiological benefits of sleep may be compromised by short sleep durations. Our hypothesis highlights possible long-term side effects of medications that reduce sleep, and may lead to potential new strategies for preventing and treating AD. © The Author(s) 2017. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Physiologic monitoring. A guide to networking your monitoring systems.

PubMed

2011-10-01

There are many factors to consider when choosing a physiologic monitoring system. not only should these systems perform well clinically, but they should also be able to exchange data with other information systems. We discuss some of the ins and outs of physiologic monitoring system networking and highlight eight product lines from seven suppliers.

Pharmacological Treatment of Obesity in Children and Adolescents: Present and Future

PubMed Central

Iughetti, Lorenzo; China, Mariachiara; Berri, Rossella; Predieri, Barbara

2011-01-01

The prevalence of overweight and obesity is increasing in children and adolescents worldwide raising the question on the approach to this condition because of the potential morbidity, mortality, and economic tolls. Dietetic and behavioral treatments alone have only limited success; consequently, discussion on strategies for treating childhood and adolescent obesity has been promoted. Considering that our knowledge on the physiological systems regulating food intake and body weight is considerably increased, many studies have underlined the scientific and clinical relevance of potential treatments based on management of peripheral or central neuropeptides signals by drugs. In this paper, we analyze the data on the currently approved obesity pharmacological treatment suggesting the new potential drugs. PMID:21197151

The developmental psychopathology of irritability

PubMed Central

LEIBENLUFT, ELLEN; STODDARD, JOEL

2015-01-01

Chronic, severe irritability is common in childhood and is very impairing. Furthermore, childhood irritability predicts suicidality, social impairment, and depressive and anxiety disorders in adulthood. Focusing on both normative and pathologic development, we review the construct of irritability from its origins in aggression and disruptive behavior research to its contemporary relevance for affective psychopathology. We then describe two broad neurocognitive systems that show promise in differentiating irritable from nonirritable youths: aberrant processing of emotional stimuli and impaired context-sensitive regulation. We suggest behavioral, neurocognitive, and physiologic measures that may aid in studying severe irritability and assessing its therapeutics. Finally, we argue for therapeutic trials targeting severe irritability that address emotional aspects of irritability in addition to the associated disruptive behavior. PMID:24342851

Intestinal alkaline phosphatase: a summary of its role in clinical disease.

PubMed

Fawley, Jason; Gourlay, David M

2016-05-01

Over the past few years, there is increasing evidence implicating a novel role for Intestinal Alkaline Phosphatase (IAP) in mitigating inflammatory mediated disorders. IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons, we sought to review recent research in both animal and humans on IAP's physiologic function, mechanisms of action and current research in specific surgical diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Cell death and survival signalling in the cardiovascular system.

PubMed

Tucka, Joanna; Bennett, Martin; Littlewood, Trevor

2012-01-01

The loss of cells is an important factor in many diseases, including those of the cardiovascular system. Whereas apoptosis is an essential process in development and tissue homeostasis, its occurrence is often associated with various pathologies. Apoptosis of neurons that fail to make appropriate connections is essential for the selection of correct neural signalling in the developing embryo, but its appearance in adults is often associated with neurodegenerative disease. Similarly, in the cardiovascular system, remodeling of the mammalian outflow tract during the transition from a single to dual series circulation with four chambers is accompanied by a precise pattern of cell death, but apoptosis of cardiomyocytes contributes to ischemia-reperfusion injury in the heart. In many cases, it is unclear whether apoptosis represents a causative association or merely a consequence of the disease itself. There are many excellent reviews on cell death in the cardiovascular system (1-5); in this review we outline the critical signalling pathways that promote the survival of cardiovascular cells, and their relevance to both physiological cell death and disease.

Microscale screening systems for 3D cellular microenvironments: platforms, advances, and challenges

PubMed Central

Montanez-Sauri, Sara I.; Beebe, David J.; Sung, Kyung Eun

2015-01-01

The increasing interest in studying cells using more in vivo-like three-dimensional (3D) microenvironments has created a need for advanced 3D screening platforms with enhanced functionalities and increased throughput. 3D screening platforms that better mimic in vivo microenvironments with enhanced throughput would provide more in-depth understanding of the complexity and heterogeneity of microenvironments. The platforms would also better predict the toxicity and efficacy of potential drugs in physiologically relevant conditions. Traditional 3D culture models (e.g. spinner flasks, gyratory rotation devices, non-adhesive surfaces, polymers) were developed to create 3D multicellular structures. However, these traditional systems require large volumes of reagents and cells, and are not compatible with high throughput screening (HTS) systems. Microscale technology offers the miniaturization of 3D cultures and allows efficient screening of various conditions. This review will discuss the development, most influential works, and current advantages and challenges of microscale culture systems for screening cells in 3D microenvironments. PMID:25274061

Know your neighbor: Microbiota and host epithelial cells interact locally to control intestinal function and physiology.

PubMed

Sommer, Felix; Bäckhed, Fredrik

2016-05-01

Interactions between the host and its associated microbiota differ spatially and the local cross talk determines organ function and physiology. Animals and their organs are not uniform but contain several functional and cellular compartments and gradients. In the intestinal tract, different parts of the gut carry out different functions, tissue structure varies accordingly, epithelial cells are differentially distributed and gradients exist for several physicochemical parameters such as nutrients, pH, or oxygen. Consequently, the microbiota composition also differs along the length of the gut, but also between lumen and mucosa of the same intestinal segment, and even along the crypt-villus axis in the epithelium. Thus, host-microbiota interactions are highly site-specific and the local cross talk determines intestinal function and physiology. Here we review recent advances in our understanding of site-specific host-microbiota interactions and discuss their functional relevance for host physiology. © 2016 WILEY Periodicals, Inc.

Physiologic basis for understanding quantitative dehydration assessment.

PubMed

Cheuvront, Samuel N; Kenefick, Robert W; Charkoudian, Nisha; Sawka, Michael N

2013-03-01

Dehydration (body water deficit) is a physiologic state that can have profound implications for human health and performance. Unfortunately, dehydration can be difficult to assess, and there is no single, universal gold standard for decision making. In this article, we review the physiologic basis for understanding quantitative dehydration assessment. We highlight how phenomenologic interpretations of dehydration depend critically on the type (dehydration compared with volume depletion) and magnitude (moderate compared with severe) of dehydration, which in turn influence the osmotic (plasma osmolality) and blood volume-dependent compensatory thresholds for antidiuretic and thirst responses. In particular, we review new findings regarding the biological variation in osmotic responses to dehydration and discuss how this variation can help provide a quantitative and clinically relevant link between the physiology and phenomenology of dehydration. Practical measures with empirical thresholds are provided as a starting point for improving the practice of dehydration assessment.

PhysioNet: physiologic signals, time series and related open source software for basic, clinical, and applied research.

PubMed

Moody, George B; Mark, Roger G; Goldberger, Ary L

2011-01-01

PhysioNet provides free web access to over 50 collections of recorded physiologic signals and time series, and related open-source software, in support of basic, clinical, and applied research in medicine, physiology, public health, biomedical engineering and computing, and medical instrument design and evaluation. Its three components (PhysioBank, the archive of signals; PhysioToolkit, the software library; and PhysioNetWorks, the virtual laboratory for collaborative development of future PhysioBank data collections and PhysioToolkit software components) connect researchers and students who need physiologic signals and relevant software with researchers who have data and software to share. PhysioNet's annual open engineering challenges stimulate rapid progress on unsolved or poorly solved questions of basic or clinical interest, by focusing attention on achievable solutions that can be evaluated and compared objectively using freely available reference data.

Resilience in Aging Mice

PubMed Central

Kirkland, James L.; Stout, Michael B.

2016-01-01

Abstract Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance health span and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience. Thus, a test for resilience at middle age or even earlier could represent a surrogate approach to test the hypothesis that an intervention delays the process of aging itself. For this, animal models to test resilience accurately and predictably are needed. In addition, interventions that increase resilience might lead to treatments aimed at enhancing recovery following acute illnesses, or preventing poor outcomes from medical interventions in older, prefrail subjects. At a meeting of basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly, the merits and drawbacks of investigating effects of interventions on resilience in mice were considered. Available and potential stressors for assessing physiological resilience as well as the notion of developing a limited battery of such stressors and how to rank them were discussed. Relevant ranking parameters included value in assessing general health (as opposed to focusing on a single physiological system), ease of use, cost, reproducibility, clinical relevance, and feasibility of being repeated in the same animal longitudinally. During the discussions it became clear that, while this is an important area, very little is known or established. Much more research is needed in the near future to develop appropriate tests of resilience in animal models within an aging context. The preliminary set of tests ranked by the participants is discussed here, recognizing that this is a first attempt. PMID:27535963

Cardiorespiratory assessment of decongestant-antihistamine effects of altitude, +Gz, and fatigue tolerances.

DOT National Transportation Integrated Search

1978-04-01

Decongestants and antihistamines are known to produce effects capable of adversely modifying physiological function and psychomotor task performance. Because of relevance to safe pilot performance, the effects of single doses of two decongestant-anti...

Driving Human Motor Cortical Oscillations Leads to Behaviorally Relevant Changes in Local GABAA Inhibition: A tACS-TMS Study

PubMed Central

van Ede, Freek

2017-01-01

Beta and gamma oscillations are the dominant oscillatory activity in the human motor cortex (M1). However, their physiological basis and precise functional significance remain poorly understood. Here, we used transcranial magnetic stimulation (TMS) to examine the physiological basis and behavioral relevance of driving beta and gamma oscillatory activity in the human M1 using transcranial alternating current stimulation (tACS). tACS was applied using a sham-controlled crossover design at individualized intensity for 20 min and TMS was performed at rest (before, during, and after tACS) and during movement preparation (before and after tACS). We demonstrated that driving gamma frequency oscillations using tACS led to a significant, duration-dependent decrease in local resting-state GABAA inhibition, as quantified by short interval intracortical inhibition. The magnitude of this effect was positively correlated with the magnitude of GABAA decrease during movement preparation, when gamma activity in motor circuitry is known to increase. In addition, gamma tACS-induced change in GABAA inhibition was closely related to performance in a motor learning task such that subjects who demonstrated a greater increase in GABAA inhibition also showed faster short-term learning. The findings presented here contribute to our understanding of the neurophysiological basis of motor rhythms and suggest that tACS may have similar physiological effects to endogenously driven local oscillatory activity. Moreover, the ability to modulate local interneuronal circuits by tACS in a behaviorally relevant manner provides a basis for tACS as a putative therapeutic intervention. SIGNIFICANCE STATEMENT Gamma oscillations have a vital role in motor control. Using a combined tACS-TMS approach, we demonstrate that driving gamma frequency oscillations modulates GABAA inhibition in the human motor cortex. Moreover, there is a clear relationship between the change in magnitude of GABAA inhibition induced by tACS and the magnitude of GABAA inhibition observed during task-related synchronization of oscillations in inhibitory interneuronal circuits, supporting the hypothesis that tACS engages endogenous oscillatory circuits. We also show that an individual's physiological response to tACS is closely related to their ability to learn a motor task. These findings contribute to our understanding of the neurophysiological basis of motor rhythms and their behavioral relevance and offer the possibility of developing tACS as a therapeutic tool. PMID:28348136

Detection and quantification of S-nitrosoglutathione (GSNO) in pepper (Capsicum annuum L.) plant organs by LC-ES/MS.

PubMed

Airaki, Morad; Sánchez-Moreno, Lourdes; Leterrier, Marina; Barroso, Juan B; Palma, José M; Corpas, Francisco J

2011-11-01

Glutathione (GSH) is one of the major, soluble, low molecular weight antioxidants, as well as the major non-protein thiol in plant cells. However, the relevance of this molecule could be even greater considering that it can react with nitric oxide (NO) to generate S-nitrosoglutathione (GSNO) which is considered to function as a mobile reservoir of NO bioactivity in plants. Although this NO-derived molecule has an increased physiological and phytopathological relevance in plants cells, its identification and quantification in plant tissues have not be reported so far. Using liquid chromatography-electrospray/mass spectrometry (LC-ES/MS), a method was set up to detect and quantify simultaneously GSNO as well reduced and oxidized glutathione (GSH and GSSG, respectively) in different pepper plant organs including roots, stems and leaves, and in Arabidopsis leaves. The analysis of NO and GSNO reductase (GSNOR) activity in these pepper organs showed that the content of GSNO was directly related to the content of NO in each organ and oppositely related to the GSNOR activity. This approach opens up new analytical possibilities to understand the relevance of GSNO in plant cells under physiological and stress conditions.

A physiologically informed virtual reality based social communication system for individuals with autism.

PubMed

Lahiri, Uttama; Bekele, Esubalew; Dohrmann, Elizabeth; Warren, Zachary; Sarkar, Nilanjan

2015-04-01

Clinical applications of advanced technology may hold promise for addressing impairments associated with autism spectrum disorders (ASD). This project evaluated the application of a novel physiologically responsive virtual reality based technological system for conversation skills in a group of adolescents with ASD. The system altered components of conversation based on (1) performance alone or (2) the composite effect of performance and physiological metrics of predicted engagement (e.g., gaze pattern, pupil dilation, blink rate). Participants showed improved performance and looking pattern within the physiologically sensitive system as compared to the performance based system. This suggests that physiologically informed technologies may have the potential of being an effective tool in the hands of interventionists.

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

PubMed Central

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-01-01

Within the framework of ‘Network Physiology’, we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain–heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain–heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems. PMID:27044991

[Anatomy, physiology and clinical relevance of the connecting tubule].

PubMed

Miranda, N; Simeoni, M A; Ciriana, E; Panico, C; Cappello, E; Capasso, G B

2009-01-01

The cortical distal nephron is the site of fine regulation of salt and water excretion by peptide and mineralocorticoid hormones and the site for specific actions of diuretics. Some data suggest that sodium reabsorption and potassium secretion in the distal convoluted tubule and the connecting tubule (CNT) are sufficient to maintain the sodium and potassium balance, with little or no contribution of the collecting duct. The homeostatic role of the sodium and potassium transport systems in the collecting duct can be questioned, especially in conditions where dietary sodium intake is high and potassium intake is low compared with the physiological needs of the organism. The functional expression of epithelial sodium channels (ENaC) in the CNT is sufficient for furosemide-stimulated urinary acidification and identifies the CNT as a major segment in electrogenic urinary acidification. In the outer renal cortex, the CNT returns to the glomerular hilus and contacts the renal afferent arterioles (Af-Art). This morphology is compatible with a cross-talk between the CNT and Af-Art. This novel regulatory mechanism of the renal microcirculation may participate in the vasodilatation observed during high salt intake, perhaps by antagonizing tubuloglomerular feedback. In conclusion, the cortical distal nephron appears to be a complex site for several physiological mechanisms; it is mainly involved in salt and fluid homeostasis and in acid-base balance maintenance. Furthermore, the CNT segment appears to promote a CNT-Af-Art feedback loop.

Heat stress and dehydration in adapting for performance: Good, bad, both, or neither?

PubMed Central

Akerman, Ashley Paul; Tipton, Michael; Minson, Christopher T.; Cotter, James David

2016-01-01

ABSTRACT Physiological systems respond acutely to stress to minimize homeostatic disturbance, and typically adapt to chronic stress to enhance tolerance to that or a related stressor. It is legitimate to ask whether dehydration is a valuable stressor in stimulating adaptation per se. While hypoxia has had long-standing interest by athletes and researchers as an ergogenic aid, heat and nutritional stressors have had little interest until the past decade. Heat and dehydration are highly interlinked in their causation and the physiological strain they induce, so their individual roles in adaptation are difficult to delineate. The effectiveness of heat acclimation as an ergogenic aid remains unclear for team sport and endurance athletes despite several recent studies on this topic. Very few studies have examined the potential ergogenic (or ergolytic) adaptations to ecologically-valid dehydration as a stressor in its own right, despite longstanding evidence of relevant fluid-regulatory adaptations from short-term hypohydration. Transient and self-limiting dehydration (e.g., as constrained by thirst), as with most forms of stress, might have a time and a place in physiological or behavioral adaptations independently or by exacerbating other stressors (esp. heat); it cannot be dismissed without the appropriate evidence. The present review did not identify such evidence. Future research should identify how the magnitude and timing of dehydration might augment or interfere with the adaptive processes in behaviorally constrained versus unconstrained humans. PMID:28349082

Heat stress and dehydration in adapting for performance: Good, bad, both, or neither?

PubMed

Akerman, Ashley Paul; Tipton, Michael; Minson, Christopher T; Cotter, James David

2016-01-01

Physiological systems respond acutely to stress to minimize homeostatic disturbance, and typically adapt to chronic stress to enhance tolerance to that or a related stressor. It is legitimate to ask whether dehydration is a valuable stressor in stimulating adaptation per se . While hypoxia has had long-standing interest by athletes and researchers as an ergogenic aid, heat and nutritional stressors have had little interest until the past decade. Heat and dehydration are highly interlinked in their causation and the physiological strain they induce, so their individual roles in adaptation are difficult to delineate. The effectiveness of heat acclimation as an ergogenic aid remains unclear for team sport and endurance athletes despite several recent studies on this topic. Very few studies have examined the potential ergogenic (or ergolytic) adaptations to ecologically-valid dehydration as a stressor in its own right, despite longstanding evidence of relevant fluid-regulatory adaptations from short-term hypohydration. Transient and self-limiting dehydration (e.g., as constrained by thirst), as with most forms of stress, might have a time and a place in physiological or behavioral adaptations independently or by exacerbating other stressors (esp. heat); it cannot be dismissed without the appropriate evidence. The present review did not identify such evidence. Future research should identify how the magnitude and timing of dehydration might augment or interfere with the adaptive processes in behaviorally constrained versus unconstrained humans.

Anatomy and Physiology. Module Set II: Major Body Systems. Teacher Edition [and] Student Edition. Surgical Technology.

ERIC Educational Resources Information Center

Hilley, Robert

This document, which is the second part of a two-part set of modules on anatomy and physiology for future surgical technicians, contains the teacher and student editions of an introduction to anatomy and physiology that consists of modules on the following body systems: integumentary system; skeletal system; muscular system; nervous system;…

Physiological regulation and metabolic role of browning in white adipose tissue.

PubMed

Jankovic, Aleksandra; Otasevic, Vesna; Stancic, Ana; Buzadzic, Biljana; Korac, Aleksandra; Korac, Bato

2017-09-01

Great progress has been made in our understanding of the browning process in white adipose tissue (WAT) in rodents. The recognition that i) adult humans have physiologically inducible brown adipose tissue (BAT) that may facilitate resistance to obesity and ii) that adult human BAT molecularly and functionally resembles beige adipose tissue in rodents, reignited optimism that obesity and obesity-related diabetes type 2 can be battled by controlling the browning of WAT. In this review the main cellular mechanisms and molecular mediators of browning of WAT in different physiological states are summarized. The relevance of browning of WAT in metabolic health is considered primarily through a modulation of biological role of fat tissue in overall metabolic homeostasis.

The conservation physiology toolbox: status and opportunities

PubMed Central

Love, Oliver P; Hultine, Kevin R

2018-01-01

Abstract For over a century, physiological tools and techniques have been allowing researchers to characterize how organisms respond to changes in their natural environment and how they interact with human activities or infrastructure. Over time, many of these techniques have become part of the conservation physiology toolbox, which is used to monitor, predict, conserve, and restore plant and animal populations under threat. Here, we provide a summary of the tools that currently comprise the conservation physiology toolbox. By assessing patterns in articles that have been published in ‘Conservation Physiology’ over the past 5 years that focus on introducing, refining and validating tools, we provide an overview of where researchers are placing emphasis in terms of taxa and physiological sub-disciplines. Although there is certainly diversity across the toolbox, metrics of stress physiology (particularly glucocorticoids) and studies focusing on mammals have garnered the greatest attention, with both comprising the majority of publications (>45%). We also summarize the types of validations that are actively being completed, including those related to logistics (sample collection, storage and processing), interpretation of variation in physiological traits and relevance for conservation science. Finally, we provide recommendations for future tool refinement, with suggestions for: (i) improving our understanding of the applicability of glucocorticoid physiology; (ii) linking multiple physiological and non-physiological tools; (iii) establishing a framework for plant conservation physiology; (iv) assessing links between environmental disturbance, physiology and fitness; (v) appreciating opportunities for validations in under-represented taxa; and (vi) emphasizing tool validation as a core component of research programmes. Overall, we are confident that conservation physiology will continue to increase its applicability to more taxa, develop more non-invasive techniques, delineate where limitations exist, and identify the contexts necessary for interpretation in captivity and the wild. PMID:29942517

Structure-Function Relations in Physiology Education: Where's the Mechanism?

ERIC Educational Resources Information Center

Lira, Matthew E.; Gardner, Stephanie M.

2017-01-01

Physiology demands systems thinking: reasoning within and between levels of biological organization and across different organ systems. Many physiological mechanisms explain how structures and their properties interact at one level of organization to produce emergent functions at a higher level of organization. Current physiology principles, such…

The role of hydroxo-bridged dinuclear species and the influence of "innocent" buffers in the reactivity of cis-[Co(III)(cyclen)(H₂O)₂]³⁺ and [Co(III)(tren)(H₂O)₂]³⁺ complexes with biologically relevant ligands at physiological pH.

PubMed

Basallote, Manuel G; Martínez, Manuel; Vázquez, Marta

2014-07-28

In view of the relevance of the reactivity of inert tetraamine Co(III) complexes having two substitutionally active cis positions capable of interact with biologically relevant ligands, the study of the reaction of cis-[Co(cyclen)(H2O)2](3+) and [Co(tren)(H2O)2](3+) with chlorides, inorganic phosphate and 5'-CMP (5'-cytidinemonophosphate) has been pursued at physiological pH. The results indicate that, in addition to the actuation of the expected labilising conjugate-base mechanism, the formation of mono and inert bis hydroxo-bridged species is relevant for understanding their speciation and reactivity. The reactivity pattern observed also indicates the key role played by the "innocent" buffers frequently used in most in vitro studies, which can make the results unreliable in many cases. The differences between the reactivity of inorganic and biologically relevant phosphates has also been found to be remarkable, with outer-sphere hydrogen bonding interactions being a dominant factor for the process. While for the inorganic phosphate substitution process the formation of μ-η(2)-OPO2O represents the termination of the reactivity monitored, for 5'-CMP only the formation of η(1)-OPO3 species is observed, which evolve with time to the final dead-end bis hydroxo-bridged complexes. The promoted hydrolysis of the 5'-CMP phosphate has not been observed in any of the processes studied.

Madres para la Salud: design of a theory-based intervention for postpartum Latinas.

PubMed

Keller, Colleen; Records, Kathie; Ainsworth, Barbara; Belyea, Michael; Permana, Paska; Coonrod, Dean; Vega-López, Sonia; Nagle-Williams, Allison

2011-05-01

Weight gain in young women suggests that childbearing may be an important contributor to the development of obesity in women. Depressive symptoms can interfere with resumption of normal activity levels following childbirth or with the initiation of or adherence to physical activity programs essential for losing pregnancy weight. Depression symptoms may function directly to promote weight gain through a physiologic mechanism. Obesity and its related insulin resistance may contribute to depressed mood physiologically. Although physical activity has well-established beneficial effects on weight management and depression, women tend to under participate in physical activity during childbearing years. Further, the mechanisms underpinning the interplay of overweight, obesity, physical activity, depression, and inflammatory processes are not clearly explained. This report describes the theoretical rationale, design considerations, and cultural relevance for "Madres para la Salud" [Mothers for Health]. Madres para la Salud is a 12 month prospective, randomized controlled trial exploring the effectiveness of a culturally specific intervention using "bouts" of physical activity to effect changes in body fat, systemic and fat tissue inflammation, and postpartum depression symptoms in sedentary postpartum Latinas. The significance and innovation of Madres para la Salud includes use of a theory-driven approach to intervention, specification and cultural relevance of a social support intervention, use of a Promotora model to incorporate cultural approaches, use of objective measures of physical activity in post partum Latinas women, and the examination of biomarkers indicative of cardiovascular risk related to physical activity behaviors in postpartum Latinas. Copyright © 2011 Elsevier Inc. All rights reserved.

Madres para la Salud: Design of a Theory-based Intervention for Postpartum Latinas

PubMed Central

Keller, Colleen; Records, Kathie; Ainsworth, Barbara; Belyea, Michael; Permana, Paska; Coonrod, Dean; Vega-López, Sonia; Nagle-Williams, Allison

2011-01-01

Background Weight gain in young women suggests that childbearing may be an important contributor to the development of obesity in women. Depressive symptoms can interfere with resumption of normal activity levels following childbirth or with the initiation of or adherence to physical activity programs essential for losing pregnancy weight. Depression symptoms may function directly to promote weight gain through a physiologic mechanism. Obesity and its related insulin resistance may contribute to depressed mood physiologically. Although physical activity has well-established beneficial effects on weight management and depression, women tend to under participate in physical activity during childbearing years. Further, the mechanisms underpinning the interplay of overweight, obesity, physical activity, depression, and inflammatory processes are not clearly explained. Objectives This report describes the theoretical rationale, design considerations, and cultural relevance for “Madres para la Salud” [Mothers for Health]. Design and Methods Madres para la Salud is a 12 month prospective, randomized controlled trial exploring the effectiveness of a culturally specific intervention using “bouts” of physical activity to effect changes in body fat, systemic and fat tissue inflammation, and postpartum depression symptoms in sedentary postpartum Latinas. Summary The significance and innovation of Madres para la Salud includes use of a theory-driven approach to intervention, specification and cultural relevance of a social support intervention, use of a Promotora model to incorporate cultural approaches, use of objective measures of physical activity in post partum Latinas women, and the examination of biomarkers indicative of cardiovascular risk related to physical activity behaviors in postpartum Latinas. PMID:21238614

Leptin and reproduction: a review.

PubMed

Moschos, Stergios; Chan, Jean L; Mantzoros, Christos S

2002-03-01

To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. A MEDLINE computer search was performed to identify relevant articles. Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.

Global expression studies in baker's yeast reveal target genes for the improvement of industrially-relevant traits: the cases of CAF16 and ORC2.

PubMed

Pérez-Torrado, Roberto; Panadero, Joaquín; Hernández-López, María José; Prieto, José Antonio; Randez-Gil, Francisca

2010-07-13

Recent years have seen a huge growth in the market of industrial yeasts with the need for strains affording better performance or to be used in new applications. Stress tolerance of commercial Saccharomyces cerevisiae yeasts is, without doubt, a trait that needs improving. Such trait is, however, complex, and therefore only in-depth knowledge of their biochemical, physiological and genetic principles can help us to define improvement strategies and to identify the key factors for strain selection. We have determined the transcriptional response of commercial baker's yeast cells to both high-sucrose and lean dough by using DNA macroarrays and liquid dough (LD) model system. Cells from compressed yeast blocks display a reciprocal transcription program to that commonly reported for laboratory strains exposed to osmotic stress. This discrepancy likely reflects differences in strain background and/or experimental design. Quite remarkably, we also found that the transcriptional response of starved baker's yeast cells was qualitatively similar in the presence or absence of sucrose in the LD. Nevertheless, there was a set of differentially regulated genes, which might be relevant for cells to adapt to high osmolarity. Consistent with this, overexpression of CAF16 or ORC2, two transcriptional factor-encoding genes included in this group, had positive effects on leavening activity of baker's yeast. Moreover, these effects were more pronounced during freezing and frozen storage of high-sucrose LD. Engineering of differentially regulated genes opens the possibility to improve the physiological behavior of baker's yeast cells under stress conditions like those encountered in downstream applications.

Pancreatic stone protein (lithostathine), a physiologically relevant pancreatic calcium carbonate crystal inhibitor?

PubMed

Bimmler, D; Graf, R; Scheele, G A; Frick, T W

1997-01-31

Apart from digestive enzymes, pancreatic juice contains several proteins that are not directly involved in digestion. One of these, lithostathine, has been reported to exhibit calcite crystal inhibitor activity in vitro. As pancreatic juice is supersaturated with respect to calcium carbonate, it was hypothesized that lithostathine stabilizes pancreatic juice. Lithostathine is cleaved by trace amounts of trypsin, resulting in a C-terminal polypeptide and an N-terminal undecapeptide, which has been identified as the active site of lithostathine regarding crystal inhibition. We produced rat lithostathine in a baculovirus expression system. In order to test its functional activity, the protein was purified using a nondenaturing multi-step procedure. In the low micromolar range, recombinant rat lithostathine in vitro exhibited calcite crystal inhibitor activity, confirming earlier reports. Limited tryptic proteolysis of recombinant lithostathine was performed, and the two cleavage products were separated; the C-terminal polypeptide was precipitated by centrifugation, and the N-terminal undecapeptide was purified by high performance liquid chromatography. Only the C-terminal peptide displayed measurable calcite crystal inhibitory activity. Furthermore, synthetic undecapeptides with identical sequence to the N-terminal undecapeptides of rat or human lithostathine were inactive. However, when tested in the same in vitro assays, other pancreatic or extra-pancreatic proteins show inhibitory activity in the same concentration range as lithostathine, and inorganic phosphate is active as well. Based on these findings it seems unlikely that lithostathine is a physiologically relevant calcite crystal inhibitor. The name "lithostathine" is therefore inappropriate, and the protein's key function remains to be elucidated.

Combining the ‘bottom up’ and ‘top down’ approaches in pharmacokinetic modelling: fitting PBPK models to observed clinical data

PubMed Central

Tsamandouras, Nikolaos; Rostami-Hodjegan, Amin; Aarons, Leon

2015-01-01

Pharmacokinetic models range from being entirely exploratory and empirical, to semi-mechanistic and ultimately complex physiologically based pharmacokinetic (PBPK) models. This choice is conditional on the modelling purpose as well as the amount and quality of the available data. The main advantage of PBPK models is that they can be used to extrapolate outside the studied population and experimental conditions. The trade-off for this advantage is a complex system of differential equations with a considerable number of model parameters. When these parameters cannot be informed from in vitro or in silico experiments they are usually optimized with respect to observed clinical data. Parameter estimation in complex models is a challenging task associated with many methodological issues which are discussed here with specific recommendations. Concepts such as structural and practical identifiability are described with regards to PBPK modelling and the value of experimental design and sensitivity analyses is sketched out. Parameter estimation approaches are discussed, while we also highlight the importance of not neglecting the covariance structure between model parameters and the uncertainty and population variability that is associated with them. Finally the possibility of using model order reduction techniques and minimal semi-mechanistic models that retain the physiological-mechanistic nature only in the parts of the model which are relevant to the desired modelling purpose is emphasized. Careful attention to all the above issues allows us to integrate successfully information from in vitro or in silico experiments together with information deriving from observed clinical data and develop mechanistically sound models with clinical relevance. PMID:24033787

Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions.

PubMed

La, Christian; Garcia-Ramos, Camille; Nair, Veena A; Meier, Timothy B; Farrar-Edwards, Dorothy; Birn, Rasmus; Meyerand, Mary E; Prabhakaran, Vivek

2016-01-01

Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the "default-mode" network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction (PPI) analysis demonstrated an independence of these two systems, with the onset of task not influencing the correlation between the two systems. Our results suggest that the language network and the DMN may be non-dependent systems, potentially correlated through the re-allocation of cortical resources, and that aging may affect those two systems differently.