Teaching cardiovascular physiology with equivalent electronic circuits in a practically oriented teaching module

Here, we report on a new tool for teaching cardiovascular physiology and pathophysiology that promotes qualitative as well as quantitative thinking about time-dependent physiological phenomena. Quantification of steady and presteady-state (transient) cardiovascular phenomena is traditionally done by differential equations, but this is time consuming and unsuitable for most undergraduate medical students. As a result, quantitative thinking about time-dependent physiological phenomena is often not extensively dealt with in an undergraduate physiological course. However, basic concepts of steady and presteady state can be explained with relative simplicity, without the introduction of differential equation, with equivalent electronic circuits (EECs). We introduced undergraduate medical students to the concept of simulating cardiovascular phenomena with EECs. EEC simulations facilitate the understanding of simple or complex time-dependent cardiovascular physiological phenomena by stressing the analogies between EECs and physiological processes. Student perceptions on using EEC to simulate, study, and understand cardiovascular phenomena were documented over a 9-yr period, and the impact of the course on the students' knowledge of selected basic facts and concepts in cardiovascular physiology was evaluated over a 3-yr period. We conclude that EECs are a valuable tool for teaching cardiovascular physiology concepts and that EECs promote active learning.     

What we talk about when we talk with medical students

In this article, we review how we interact with medical students in our efforts to teach blood pressure regulation and systemic cardiovascular control along with related elements of respiratory and exercise physiology. Rather than provide a detailed lecture with key facts, we attempted to outline our approach to teaching integrative cardiovascular physiology to medical students, which includes five major themes. First, focus on questions versus answers and facts. We believe that this offers both the learner and teacher a number of advantages. Second, avoid teaching dogma in the name of clarity (i.e., heavy focus on teaching "facts" that have not yet been fully investigated). This is especially important because of the way knowledge evolves over time. Third, include laboratory-based experiences in human integrative physiology. Fourth, provide students with intellectual frameworks versus a list of "facts" to serve as a platform for question generation. Finally, focus on the role of integration and regulatory redundancy in physiology and the idea that physiology is a narrative that can help. In this article, we discuss the philosophy behind the themes outlined above and argue that questions, and not answers, are where the action is for both research and education.     

Using a course-long theme for inquiry-based laboratories in a comparative physiology course

I developed an inquiry-based laboratory model that uses a central theme throughout the semester to develop in undergraduate biology majors the skills required for conducting science while introducing them to modern and classical physiological techniques. The physiology laboratory uses a goal-oriented approach, with students working cooperatively in small groups to answer basic biological questions. The student teams work to develop skills associated with experimental design, data analysis, written and oral communication, science literacy, and critical thinking. The laboratory curriculum is a research-based model that offers the advantage of students asking open-ended questions by use of a variety of techniques. For the students and instructor alike, this presents an exciting and challenging approach for learning physiology and basic biological principles. Another advantage of this laboratory model is that it is flexible and adaptable; the central theme can be any that the instructor chooses, and the goals and techniques developed are based on student and instructor needs and interests. Students who have completed this model at Loyola College in Maryland have become equipped with the skills essential for any area of the biological sciences and, most importantly, showed elevated excitement and commitment to learning.     

A conceptual framework for studying the strength of plant–animal mutualistic interactions

The strength of species interactions influences strongly the structure and dynamics of ecological systems. Thus, quantifying such strength is crucial to understand how species interactions shape communities and ecosystems. Although the concepts and measurement of interaction strength in food webs have received much attention, there has been comparatively little progress in the context of mutualism. We propose a conceptual scheme for studying the strength of plant–animal mutualistic interactions. We first review the interaction strength concepts developed for food webs, and explore how these concepts have been applied to mutualistic interactions. We then outline and explain a conceptual framework for defining ecological effects in plant–animal mutualisms. We give recommendations for measuring interaction strength from data collected in field studies based on a proposed approach for the assessment of interaction strength in plant–animal mutualisms. This approach is conceptually integrative and methodologically feasible, as it focuses on two key variables usually measured in field studies: the frequency of interactions and the fitness components influenced by the interactions.     

Sleep as a teaching tool for integrating respiratory physiology and motor control

Sleep exerts major effects on most fundamental homeostatic mechanisms. Current data suggest, however, that students of physiology and medicine typically receive little or no formal teaching in sleep. Because sleep takes up a significant component of our life span, it is proposed that current teaching in systems and integrative physiology is not representative if it is confined to functions describing wakefulness only. We propose that sleep can be readily integrated into various components of physiology and medical curricula simply by emphasizing how commonly taught physiological processes are importantly affected by sleep mechanisms. In our experience, this approach can be used to reinforce basic physiological principles while simultaneously introducing sleep physiology into the students' training. We find that students have a general and inherent interest in sleep and related clinical disorders, and this proves useful as an effective means to teach the material. In this paper, examples of how sleep influences motor control and the respiratory system will illustrate these points. These considerations also highlight some important gaps in traditional teaching of respiratory physiology.     

A fast empirical approach to binding free energy calculations based on protein interface information

Three useful variables from the interfaces of 20 protein-protein complexes were investigated. These variables are the side-chain accessible number (N(b)), the number of hydrophilic pairs (N(pair)) and buried a polar solvent accessible surface areas (DeltaDeltaASA(apol)). An empirical model based on the three variables was developed to describe the free energy of protein associations. As the results show, the side-chain accessible numbers characterize the loss of side-chain conformational entropy of protein interactions and the effective empirical function presented here has great capability for estimating the binding free energy. It was found that the variables of interface information capture most of the significant features of protein-protein association. Also, we applied the model based on the variables as a rescoring function to docking simulations and found that it has the potential to distinguish the 'true' binding mode. It is clear that the simple and empirical scale developed here is an attractive target function for calculating binding free energy for various biological processes to rational protein design.     

Detecting the macroevolutionary signal of species interactions

Species interactions lie at the heart of many theories of macroevolution, from adaptive radiation to the Red Queen. Although some theories describe the imprint that interactions will have over long timescales, we are still missing a comprehensive understanding of the effects of interactions on macroevolution. Current research shows strong evidence for the impact of interactions on macroevolutionary patterns of trait evolution and diversification, yet many macroevolutionary studies have only a tenuous relationship to ecological studies of interactions over shorter timescales. We review current research in this area, highlighting approaches that explicitly model species interactions and connect them to broad‐scale macroevolutionary patterns. We also suggest that progress has been made by taking an integrative interdisciplinary look at individual clades. We focus on African cichlids as a case study of how this approach can be fruitful. Overall, although the evidence for species interactions shaping macroevolution is strong, further work using integrative and model‐based approaches is needed to spur progress towards understanding the complex dynamics that structure communities over time and space.     

How to hierarchize the main physiological processes responsible for phenotypic differences in large-scale screening studies?

One difficulty when analyzing the determinants at the origin of plant phenotypic differences is that measured plant traits are frequently integrative: they result from the integration of a large number of physiological processes under the control of genetic and environmental factors. In a previous report, we demonstrated that dissecting integrative traits into simpler components using a simple crop physiology model was a valuable method for detecting quantitative trait loci (QTL) related to the nitrogen nutrition for a recombinant inbred lines population of Medicago truncatula.⁷ Here, using the same data set, we demonstrate the relevance of decomposing integrative traits for understanding biological differences among phenotypes, independently of QTL detection. Two examples are given to demonstrate that the dissection of integrative traits (i.e., plant leaf area and nitrogen nutrition index) into variables representing the efficiency of the plant to extract and valorize (carbon and nitrogen) resources is an effective method to determine the stream of physiological events that leads to the final phenotype.     

Physiological Experimentation with the Crayfish Hindgut: A Student Laboratory Exercise

The purpose of the report is to describe dissection techniques for preparing the crayfish hindgut and to demonstrate how to make physiological recordings with a force transducer to monitor the strength of contraction. In addition, we demonstrate how to visually monitor peristaltic activity, which can be used as a bioassay for various peptides, biogenic amines and neurotransmitters. This preparation is amenable to student laboratories in physiology and for demonstrating pharmacological concepts to students. This preparation has been in use for over 100 years, and it still offers much as a model for investigating the generation and regulation of peristaltic rhythms and for describing the mechanisms underlying their modulation. The pharmacological assays and receptor sub-typing that were started over 50 years ago on the hindgut still contribute to research today. This robust preparation is well suited to training students in physiology and pharmacology.     

A two-component simulation model to teach respiratory mechanics

Interactive learning has been proven instrumental for the understanding of complex systems where the interaction of interdependent components is hard to envision. Due to the mechanical properties and mutual coupling of the lung and thorax, respiratory mechanics represent such a complex system, yet their understanding is essential for the diagnosis, prognosis, and treatment of various respiratory disorders. Here, we present a new mechanical model that allows for the simulation of respiratory pressure and volume changes in different ventilation modes. A bellow reflecting the "lung" is positioned within the inverted glass cylinder of a bell spirometer, which is sealed by a water lock and reflects the "thorax." A counterweight attached to springs representing the elastic properties of the chest wall lifts the glass cylinder, thus creating negative "pleural" pressure inside the cylinder and inflating the bellow. Lung volume changes as well as pleural and intrapulmonary pressures are monitored during simulations of spontaneous ventilation, forced expiration, and mechanical ventilation, allowing for construction of respiratory pressure-volume curves. The mechanical model allows for simulation of respiratory pressure changes during different ventilation modes. Individual relaxation curves constructed for the lung and thorax reflect the basic physiological characteristics of the respiratory system. In self-assessment, 232 medical students passing the physiology laboratory course rated that interactive teaching at the simulation model increased their understanding of respiratory mechanics by 70% despite extensive prior didactic teaching. Hence, the newly developed simulation model fosters students' comprehension of complex mechanical interactions and may advance the understanding of respiratory physiology.     

Computer simulation of temperature regulation and feedback control as undergratuate physiology exercises

Two exercises illustrating the application of the quantitative techniques of physics to the understanding of biological processes have been developed and tested with undergraduate physiology classes. The first exercise emphasises the utility of mathematical simulations which represent graphically the responses exhibited by physiological systems and the second exercise provides an example of the use of physical theory (in this case, the first law of thermodynamics) to model some aspect of the behavior of a complex physiological system.     

Study of physiological responses to acute carbon monoxide exposure with a human patient simulator

Human patient simulators are widely used to train health professionals and students in a clinical setting, but they also can be used to enhance physiology education in a laboratory setting. Our course incorporates the human patient simulator for experiential learning in which undergraduate university juniors and seniors are instructed to design, conduct, and present (orally and in written form) their project testing physiological adaptation to an extreme environment. This article is a student report on the physiological response to acute carbon monoxide exposure in a simulated healthy adult male and a coal miner and represents how 1) human patient simulators can be used in a nonclinical way for experiential hypothesis testing; 2) students can transition from traditional textbook learning to practical application of their knowledge; and 3) student-initiated group investigation drives critical thought. While the course instructors remain available for consultation throughout the project, the relatively unstructured framework of the assignment drives the students to create an experiment independently, troubleshoot problems, and interpret the results. The only stipulation of the project is that the students must generate an experiment that is physiologically realistic and that requires them to search out and incorporate appropriate data from primary scientific literature. In this context, the human patient simulator is a viable educational tool for teaching integrative physiology in a laboratory environment by bridging textual information with experiential investigation.     

Physiological changes in the gastrointestinal tract and host protective immunity: learning from the mouse-Trichinella spiralis model

Infection and inflammation in the gastrointestinal (GI) tract induces a number of changes in the GI physiology of the host. Experimental infections with parasites represent valuable models to study the structural and physiological changes in the GI tract. This review addresses research on the interface between the immune system and GI physiology, dealing specifically with 2 major components of intestinal physiology, namely mucin production and muscle function in relation to host defence, primarily based on studies using the mouse-Trichinella spiralis system. These studies demonstrate that the infection-induced T helper 2 type immune response is critical in generating the alterations of infection-induced mucin production and muscle function, and that this immune-mediated alteration in gut physiology is associated with host defence mechanisms. In addition, by manipulating the host immune response, it is possible to modulate the accompanying physiological changes, which may have clinical relevance. In addition to enhancing our understanding of immunological control of GI physiological changes in the context of host defence against enteric infections, the data acquired using the mouse-T. spiralis model provide a basis for understanding the pathophysiology of a wide range of GI disorders associated with altered gut physiology.     

Fishing for an ECG: a student-directed electrocardiographic laboratory using rainbow trout

Cardiac physiology is emphasized in many undergraduate physiology courses, but few nonmammalian vertebrate model systems exist that 1) can be studied fairly noninvasively, 2) are well suited for controlled experimentation, and 3) emphasize principles characteristic of the vertebrate heart. We have developed an inquiry-based undergraduate/graduate-level laboratory in cardiac physiology and electrocardiography using rainbow trout (Oncorhynchus mykiss Walbaum) and the BioPac MP30 data-acquisition system (other fish species and/or electrocardiographic recording devices can be substituted). This laboratory facilitates intensive study of vertebrate electrocardiograms (ECGs) under a variety of environmental and physiological perturbations and is ideal for use in multi-session, inquiry-based laboratory projects in animal physiology. Furthermore, students gain valuable experience in scientific inquiry, study design, following and/or developing scientific protocols, and animal care. This laboratory requires the ability to keep captive fish of at least 100 g and equipment to record ECGs. Departments meeting these requirements can adopt this technique at modest expense. Student enthusiasm and feedback were positive, and several students commented that the nonlethal methods used added to the laboratory's perceived value.     

Virtual patients and sensitivity analysis of the guyton model of blood pressure regulation: towards individualized models of whole-body physiology

Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a "virtual population" from which "virtual individuals" can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the "virtual individuals" that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models.     

An integrative model of evolutionary covariance: a symposium on body shape in fishes

A major direction of current and future biological research is to understand how multiple, interacting functional systems coordinate in producing a body that works. This understanding is complicated by the fact that organisms need to work well in multiple environments, with both predictable and unpredictable environmental perturbations. Furthermore, organismal design reflects a history of past environments and not a plan for future environments. How complex, interacting functional systems evolve, then, is a truly grand challenge. In accepting the challenge, an integrative model of evolutionary covariance is developed. The model combines quantitative genetics, functional morphology/physiology, and functional ecology. The model is used to convene scientists ranging from geneticists, to physiologists, to ecologists, to engineers to facilitate the emergence of body shape in fishes as a model system for understanding how complex, interacting functional systems develop and evolve. Body shape of fish is a complex morphology that (1) results from many developmental paths and (2) functions in many different behaviors. Understanding the coordination and evolution of the many paths from genes to body shape, body shape to function, and function to a working fish body in a dynamic environment is now possible given new technologies from genetics to engineering and new theoretical models that integrate the different levels of biological organization (from genes to ecology).     

Advanced fluorescence technologies help to resolve long-standing questions about microbial vitality

Advances in fundamental physical and optical principles applied to novel fluorescence methods are currently resulting in rapid progress in cell biology and physiology. Instrumentation devised in pioneering laboratories is becoming commercially available, and study findings are now becoming accessible. The first results have concerned mainly higher eukaryotic cells but many more developments can be expected, especially in microbiology. Until now, some important problems of cell physiology have been difficult to investigate due to interactions between probes and cells, excretion of probes from cells and the inability to make in situ observations deep within the cell, within tissues and structures. These technologies will enable microbiologists to address these topics. This Review aims at introducing the limits of current physiology evaluation techniques, the principles of new fluorescence technologies and examples of their use in this field of research for evaluating the physiological state of cells in model media, biofilms or tissue environments. Perspectives on new imaging technologies, such as super-resolution imaging and non-linear highly sensitive Raman microscopy, are also discussed. This review also serves as a reference to those wishing to explore how fluorescence technologies can be used to understand basic cell physiology in microbial systems.