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Experimental Biology 2001 March 31–April 4 New Orlando, Florida

	INTRODUCTION

TOP INTRODUCTION The American Physiological... Tutorials Workshop American Society for... Special Sessions Satellite Meetings American Society for... American Society for... Focus groups/workshops Course Career Development American Society for Nutritional... The American Association of... Special Symposia 2001 FASEB Excellence in... Presidential Symposium Presidential Address Distinguished Lecturers Workshop American Association of...

 
This year’s meeting of professional research scientists is being developed, sponsored, and coordinated by seven FASEB societies—The American Physiological Society, American Society for Biochemistry and Molecular Biology, American Society for Pharmacology and Experimental Therapeutics, American Society for Investigative Pathology, American Society for Nutritional Sciences, The American Association of Immunologists, and American Association of Anatomists—and by various guest societies. A sampling of the multidisciplinary sessions, listed by host societies, appears below. The Program and Abstract issues of The FASEB Journal contain considerably more details and are mailed to preregistrants before the meeting. For up-to-date information, visit http://www.faseb.org.

	The American Physiological Society

TOP INTRODUCTION The American Physiological... Tutorials Workshop American Society for... Special Sessions Satellite Meetings American Society for... American Society for... Focus groups/workshops Course Career Development American Society for Nutritional... The American Association of... Special Symposia 2001 FASEB Excellence in... Presidential Symposium Presidential Address Distinguished Lecturers Workshop American Association of...

 
Symposia
The Role of the Amygdala in the Physiology of Emotion
Chairs: R. Adolphs and B. Talman

The amygdala plays a key role in the regulation of autonomic and neuroendocrine responses, as well as the processing of emotion, including its relevance to the guidance of social behavior. How are these two aspects of amygdala function related? Speakers will show that the amygdala participates in the processing of emotion precisely as it participates in physiological regulation, i.e., somatic homeostasis and regulation in a very broad sense are essential aspects of all emotions. They will review the anatomy and function of amygdala in rats, monkeys, and humans and its relationship to emotion and social behavior, suggesting that the amygdala participates in cognition, emotion, and physiological regulation because all three of these processes are, in fact, critically interdependent on each other.

Programming of the Fetus in utero: Impact on Physiology in Adulthood
Chair: E. D. Albrecht

It is clear based on the results of physiological studies in animals, clinical observations, and epidemiological studies that programming of the fetus in utero has a major impact on function and well-being in adulthood. The imprinting that occurs during fetal development may be as important as genetic makeup in determining the outcome postnatally and in adulthood. Recent experiments conducted in the primate, for example, have shown that the high levels of estrogen to which the baboon fetus is exposed have a central integrative role in regulating the maturation of the fetal adrenal gland directly and indirectly. The estrogen acts on the placental 11ß-hydroxysteroid dehydrogenase enzymes that control the level of cortisol transported into the fetus, which results in activation and maturation of the fetal pituitary-adrenocortical axis. Consequently, there are striking estrogen-dependent changes in the development of the primate fetal adrenal gland that may have significant effect on endocrine function in the adult. Clinical studies in humans and studies in animals have shown that excess secretion of cortisol into the fetus causes intrauterine growth restriction, improper fetal development, and glucose intolerance in adulthood. In turn, epidemiologic studies indicate that the incidence of several diseases of adulthood (e.g., essential hypertension, cardiovascular disease, diabetes) correlates to with fetal birth weight, fetal stress, and maternal nutritional status. Experimental studies in laboratory rats are consistent with the epidemiological studies, since maternal low-protein-diet reproducibly produces elevations in blood pressure in adult offspring. Presenters are experts in the areas referenced above and will focus epigenetic programming and impact on physiological systems in adulthood. The timely symposium should interest physiologists who focus on development endocrinology reproduction, as well as individuals interested in issues of health and disease.

Tight Junctions: Convergence of Molecular and Physiologic Insights
Chair: J.M. Anderson

Intercellular tight junctions are the major barriers regulating paracellular transport. Physiologic studies beginning in the middle of the 20th century demonstrated that the barrier properties of tight junctions varied considerably among epithelia. They vary in electrical tightness and ion and size selectivity. The barrier is regulated by physiologic signals and is disrupted in pathologic conditions. Recent advances have been made in identifying the proteins that create the paracellular barrier. Mutations in mice and humans have highlighted the role of some of these proteins, and we are on the verge of being able to explain the molecular basis of the tight junctions’ properties. Speakers will address how individual tight junction proteins contribute to defining the permeability properties of paracellular transport, how the barrier is regulated by cellular signaling pathways and signals from leukocytes, and will return to unresolved physiologic questions about the tight functional permeability to water and specific solutes.

Neurohumoral Control of the Normal and Diseased Heart
Chair: J.L. Ardell

Participants will provide an overview of the neurohumoral interactions that are involved in cardiac regulation in normal and diseased hearts. The basic thesis is that neural control of the heart depends on multiple feedback systems within the heart, thorax, and central nervous system, each operating as interdependent units within this neurohumoral hierarchy in order to regulate cardiac function on a beat-to-beat basis. These multiple feedback loops operating from the level of the intrinsic cardiac nervous system to the cortex use numerous neurochemicals for synaptic transmission and modulation. Recent data have indicated that the evolution of cardiac disease may be accompanied by a corresponding remodeling not only of end-organ myocytes but also of the neurohumoral mechanisms that control them. This remodeling has important implications regarding the time-dependent cardiac therapy that uses ß-adrenergic blockade, ACE inhibitors, or angiotensin II receptor blockade. Therefore, speakers will stress not only the importance of understanding this neuronal hierarchy in normal states, but also neurohumoral regulatory mechanisms operating in specific cardiac disease states. Specific topics will include the functional organization for neural control of the heart and the interplay between neural and hormonal factors in the dynamic control of regional cardiac function; the capacity of various populations of cardiac afferent neurons to induce cardiovascular reflexes relating recently derived information concerning their complex transduction properties to the symptomatology of heart disease; recent data on intrathoracic and spinal cord neuronal interactions and how that data is related to the rationale for the clinical use of spinal cord stimulation in the treatment of angina secondary to myocardial ischemia; the role of medullary control circuits in cardiac regulation; and neurohumoral remodeling that accompanies progression into cardiac hypertrophy/congestive heart failure.

Gene Therapy for Cardiovascular Disease
Chairs: V.J. Dzau and K.H. Berecek

Speakers will present the latest findings on the effectiveness of gene therapy for the treatment and possible prevention of cardiovascular diseases.

Vagal Mechanisms of Visceral Sensation: Emerging Concepts
Chairs: C.M. Blatteis and H.E. Raybould

Approximately 80% of the axons of the vagus nerve are sensory afferents rather than parasympathetic efferents. However, the specific function of these afferents is almost completely unknown, even though they likely represent the major sensory pathway by which the brain is informed of visceral function. Recent evidence suggests that vagal afferents transduce and convey to the CNS a wide array of visceral stimuli, including those concerned with nutrient and mineral balance, gut distension, local hormone secretion, and immune and inflammatory signals. This cross-sectional symposium will focus on the diversity of the signals sensed by the vagus nerve, arising from different viscera and the functional consequences of these signals. Presentaters will cover areas of neurochemistry (expression of peptides and receptors by vagal afferents); the response of vagal afferents to different stimuli (immune mediators stress mediators nutrients); and the central pathways activated by vagal afferents. Speakers will present research results from different organ systems and emphasize the similarity and differences of vagal afferent innervation between viscera. Implications for understanding the physiology and pathophysiology of functions as diverse as pain sensitivity, mood disorders, feeding behavior, and acute and chronic inflammatory disease will also be addressed.

Genomics and Molecular Basis of Exercise and Environmental Physiology: Molecular Basis of Human Performance
Chair: C. Bouchard

It has long been suspected that there is a hereditary component to human physical performance, but the genetic basis of exercise remains elusive. This symposium will review our current knowledge of the genetic basis of human performance, discuss an emerging animal model that may enable a genetic analysis of the problem, and discuss the first gene implicated in human physical performance—angiotensin-converting enzyme.

Early Impact of Diabetic Hyperglycemia on Renal and Cardiovascular Function
Chairs: M.W. Brands and P.K. Carmines

Diabetes has long been associated with excess renal- and cardiovascular-related morbidity and mortality. Although much work over the years has focused on the pathophysiology of the established disease, emerging evidence indicates that myriad alterations in renal, cardiac, and vascular control systems are evident at the earliest stages of diabetes. Many of these alterations suggest that hemodynamic mechanisms may act in concert with direct tissue actions of hyperglycemia, beginning very early in diabetes, to promote the deleterious changes in cardiovascular tissue structure. For example, there is evidence of altered electromechanical coupling in renal preglomerular microvascular smooth muscle within two weeks of onset. There is also evidence of a marked potentiation of the effects of hyperglycemia on mesangial glycogen production by increased mechanical strain. A system with considerable potential to be involved in these processes is the nitric oxide (NO) system, which is extremely sensitive to glycemic control. Both hyperinsulinemic and hypoinsulinemic models of diabetes exhibit altered endothelial regulation of the microvasculature. Furthermore, it has been reported that NO production is required to prevent hypertension at the onset of Type I diabetes secretion. Acute (<1 h) exposure to a hyperglycemic environment provokes alterations in NO-dependent arteriolar dilation that can be attributed to oxygen radical formation. The oxidative stress associated with hyperglycemia also exerts deleterious effects on the heart and alterations in glutathione redox state might be one factor that alters K+ channel function in cardiomyocytes during the early stage of diabetes. Thus, the black box that was previously positioned between the diagnosis of diabetes and the onset of complications (such as microalbuminuria, retinopathy, and hypertension) has given way to evidence implicating early interdependent chaqnges in control systems at all levels of the cardiovascular system.

Physiology InFocus: Neurotransmitters in Cardiovascular Regulation: Nitric Oxide
Chair: D.S. Bredt

Nitric oxide (NO) is a free radical molecular messenger that mediates diverse actions, particularly on the heart and circulatory system. Though first discovered as an endothelial-derived relaxing factor, it is now clear that NO controls the cardiovascular function by regulating vasodilator nerves, oxygen transport, and cardiac contractility. Nitric oxide is produced by a family of NO synthase enzymes that are differentially expressed; they distinctly contribute to cardiovascular regulation. Targeted disruption of these genes in mice has expanded our understanding of the roles for each isoform. In addition to its physiological functions, NO as a free radical mediates cell and tissue damage in various disease states. This symposium will highlight recent advances in regulation of cardiovascular function and disease by the unique neurotransmitter NO.

Membrane Fusion
Chair: D. Brown

Numerous renal transport phenomena are governed by regulated exocytosis. In the past few years, the molecular components of the cellular fusion apparatus have been identified and their interactions elucidated. Participants will focus on the current understanding of the structure and function of the membrane fusion apparatus in general and as it applies to renal physiology.

Myosin Isoforms and Smooth Muscle Function: New Technology, New Questions
Chairs: F. Brozovich and R.J. Paul

The molecular motor myosin is present in smooth muscle in various isoforms, which are known to change during development, dependent on hormonal status such as estrogen levels, and are altered in disease states, such as hypertension. Yet the connection between isoform and function remains largely open. Speakers will address the most recent evidence arising from application of cutting-edge molecular and biophysical technology. Presentations will range from the use of laser molecular traps to study individual myosin molecules the latest electron microscopy reconstruction of myosin filament models to the function of myosin isoforms at the whole animal level uncovered using newly developed transgenic mice models.

DNA Microarray in Bioengineering and Physiology
Chair: S. Chien

The impending availability of the sequence and loci data on all human genes poses the opportunity and challenge to organize the information into a body of knowledge for the derivation of functional roles and phenotypic traits for not only the individual genes but also for families of genes in relation to one another. The next grand challenge is to decipher functional genomics (or physiological genomics) by leveraging on the knowledge derived from genomic sequencing and mapping, enabling us to elucidate biological functions in an integrative manner from genetic and molecular levels to organs and organisms. Biochip microarray systems have provided the timely new tools to meet the needs of functional genomics by furnishing a global strategy that is much more systematic and powerful than the piecemeal approach. The biochip microarray is prepared by attaching multiple nucleic acid probe molecules to a solid support (e.g., glass slide or filter). The nucleic acid molecules from the biological samples to be interrogated are labeled with fluorescent labels chromogens or radioisotopes and such labeled targets are then hybridized with the probes on the microarray. Scanning of the intensity of the label at each address on the microarray allows an assessment of the degree of hybridization between the nucleic acids in the target sample and those in the arrayed probes. The analysis of the large volume of data points requires the computational approach of bioinformatics. Thus, the effective utilization of the biochip microarray technology requires a combination of several engineering disciplines with biology and medicine, i.e., biomedical engineering.

Biochip microarray technology has great potential for solving solution hysiological problems and for application to pathophysiology and medicine. There are a few examples of the application of cDNA microarrays to study the molecular mechanisms of physiological processes, but the potential has remained virtually untapped. Bioengineers and physiologists must begin to explore the opportunity of using biochip microarray to study the molecular genetic basis of functional behavior of biological systems in an integrative approach. This will help us understand functional regulation and disturbance in health and disease.

As for the life sciences, microarrays will provide the answer to the challenge of deciphering functional genomics. In terms of clinical medicine, microarrays offer new ways of diagnosis and treatment, including the development of individualized approaches based on genetic polymorphism. Microarrays likely will become the standard tool in both life science research and clinical medicine. This is an opportunity to apply this frontier technology for research in biomedical engineering and physiology. Symposium particpants will meet this timely need of introducing the new technology of biochip microarrays, so that it can be widely used for scientific inquiries into the basic mechanisms of functional regulation and the pathophysiological basis of disease states.

Matching Technology to Education: How to Choose the Right Technology to Meet Your Educational Needs
Chairs: C.L. Cleland and J.A. Michael

The use of information technology in all aspects of education is expanding. In parallel, greater emphasis is being placed on the identification and assessment of educational goals. This symposium is designed to explore how to match educational objectives to instructional methods. In particular, it should be clear that otherwise good education and good technology can be mismatched, leading to an unexpected decrease in learning. The audience should come away with an appreciation that because of the recent proliferation of new and importantly unfamiliar technology, far more attention must be directed to the link between educational goal and instructional methodology than ever before.

Vasopressin: Integrative and Cellular Mechanisms of Release and Actions
Chairs: J.T. Cunningham and C.D. Sladek

Vasopressin, a peptide hormone that is released from the posterior pituitary by magnocellular neurosecretory cells located in the hypothalamus, functions primarily as an antidiuretic, although it can also act as a vasoconstrictor, affect sodium reabsorption, and alter autonomic reflex function. The magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus, which are responsible for production and release of vasopressin, have long been studied as a model system for understanding the neuroscience of neuroendocrine function. The functions of vasopressin have made it an area of intense study for researchers interested in understanding body fluid homeostasis. These aspects of vasopressin research make it an important intersection of neuroscience and traditional physiology involving multidisciplinary and integrative research. Recent technological advances and new scientific discoveries have increased our understanding of both the neuroscience and the physiology of vasopressin. Speakers will update recent advances in vasopressin research and provide an integrative overview of the regulation and function of vasopressin, including its role in pathophysiological states. The participants will discuss state-of-the-art approaches to study physiologically induced differential gene expression in magnocellular neurons; the use of in vitro approaches to study vasopressin release and the regulation of vasopressin gene expression and how this system is altered by steroid hormones and aging; recent work on the biophysics of magnocellular neurosecretory cells, with focus on how these neurons integrate multiple synaptic inputs; recent advances in the understanding of the neural networks that regulate the activity of vasopressin neurons in relation to changes in the internal environment; and approaches now being used to examine the actions of vasopressin on the kidney, including vasopressin escape.

Physiology InFocus: Neurotransmitters in Cardiovascular Regulation: Angiotensin
Chair: R.A.L. Dampney

The circulating hormone angiotensin II has long been known to be crucial in blood pressure regulation and fluid homeostasis. In the 1980s it was also discovered that receptors for angiotensin II in brain regions play a critical role in cardiovascular regulation such as the nucleus of the solitary tract and the ventrolateral medulla, but are not accessible to circulating angiotensin II. Recently, evidence indicates that brain angiotensin II may be of particular importance in the long-term regulation of sympathetic activity and blood pressure and may also contribute to increased sympathetic activity in cardiovascular disorders such as heart failure and some types of hypertension. Presenters will highlight recent advances in our understanding of the functions of angiotensin II in the regulation of cardiovascular neurons in the brainstem. Topics will include the cellular mechanisms of action of angiotensin II, its interactions with other transmitter systems, and its contribution to both the tonic and reflex control of blood pressure.

Neuronal Mechanisms Underlying Associative Learning
Chairs: J.M. Delgado-García and B.G. Schreurs

The classical conditioning of eyelid/nictitating membrane responses is a widely used experimental procedure for studying the neuronal mechanisms underlying associative learning and memory storage. The kinematics, frequency-domain properties, and movement topography of spontaneous reflex, passive, and conditioned eyelid responses have been described and quantified in different species, including humans. Neuronal centers involved in lid responses have been determined as well as the electrical activity in both in vivo and in vitro studies. Nevertheless, the neuronal centers where classically conditioned eyelid responses are learned and/or stored have been a matter of continuous debate for the past four decades. In particular, cerebellum, hippocampus, and other cerebral cortical structures have been implicated in a wide variety of learning and memory experimental paradigms. Participants will address this exciting issue with a comparative and multidisciplinary approach, including the consideration of studies in different species and using different technical approaches will be considered and experiments involving the main cerebral structures proposed to be the site of motor learning and/or memory storage.

Endothelial Cellular Response to Altered Shear Stress
Chairs: A.B. Fisher and P. Schumaker

There is increasing evidence that many cell types sense and respond to physical stimulae. This is especially true of endothelial cells, which are normally exposed to the flowing blood and are now known to exhibit cellular responses to shear stress. These responses may be important for a broad variety of major diseases. For example, athroferosis and other vascular changes may be secondary in part to increased or altered patterns of shear. Loss of shear with ischemia due to embolism or thrombosis may contribute to the pathophysiology more commonly associated with tissue anoxia. This symposium proposes to present the cellular adaptation and changes that occur with alteration to shear stress in endothelial cells. Presentations will include the use of pulmonary-derived endothelium, as well as endothelium derived from other sites. To date, no major qualitative differences have been described for the response to shear among the various endothelial preparation Speakers will describe the adaptation of endothelial cells in culture to initiation of flow; emphasize gene induction while describing the signaling events associated with increased shear stress; describe the signaling events that will occur with loss of shear stress in flow adapted endothelial cells; present data related to the role of ion channels and cytoskeletal elements as the shear stress sensors; and present data related to the role of mitochondria as transducers of mechanical strain. In all, presenters will the cellular responses to both increased and decreased stress and consider the roles of various sensors and transducers of the mechanical events.

Respiratory Physiology of the Pharyngeal Airway: Modulation by Skeletal Muscle Activities, Central Nervous System State, and Disease
Chairs: R.F. Fregosi and S.T. Kuna

Coordinated motor control of the pharyngeal airway is required for normal speech, swallowing, and breathing. Although motor control of all pharyngeal behaviors is important to understand, control of pharyngeal airway geometry and compliance is receiving considerable interest now because of several prevalent forms of sleep-disordered breathing, including obstructive sleep apnea and sudden infant death syndrome. Common to several forms of sleep-disordered breathing is patency of the upper airway in wakefulness and a loss of this patency in sleep. Coincident with a loss of airway patency is a reduction in upper airway dilator muscle activity. Indeed, activity of upper airway motoneurons is highly dependent of the behavioral state. Thus, for obstructive sleep apnea there are two hotly investigated areas of science: mechanisms used in maintaining a patent upper airway in wakefulness and mechanisms involved in the loss of this patency. Scientists with many different backgrounds have been exploring components of these two broad research areas. This session will bring these scientists together. They will discuss new ideas regarding the role of pharyngeal muscle activities in the control of pharyngeal airway geometry and compliance, focusing on the pharyngeal constrictor and tongue muscles, respectively; new information on the molecular mechanisms underlying pontine neuronal activities that control sleep state and respiratory motor output; the role of neurochemicals in controlling the various groups of respiratory motoneurons and the sleep-state dependency of this control; and pharyngeal airway function in patients with the obstructive sleep apnea syndrome, including the physiological basis of novel treatment approaches. This symposium should attract broad participation by scientists interested in the control of breathing pharyngeal physiology, the control of sleep-state swallowing, and airway disease.

Combined Impact of Temperature and Exercise Stress on the Physiological Response to Toxic Agents
Chairs: C.J. Gordon and J.J. Steinberg

Scientists conduct almost all toxicological and pharmacological studies with resting subjects under stable environmental conditions in which ambient temperature, relative humidity, photoperiod, and other environmental variables are maintained under standard conditions. However, this standard environment is clearly not representative of the fluctuations in the natural environment encountered by humans and animals on both a daily and annual basis. The standard test environments generally fail to assess the effects of work, exercise activity, and other behavioral choices that may substantially alter physiological responses to environmental toxicants. The physiological response to toxicants may be markedly affected when these environmental variables deviate from standard conditions. Furthermore, extrapolating toxicological effects from experimental animals to humans who are exposed to varied environmental and working conditions is clearly problematic without information on the responses of experimental animals under similarly stressful conditions. This session will focus on research that deals with the effects of temperature and exercise stress on the physiological response to toxicants. Temperature and exercise are closely related environmental physiology topics. Higher ambient temperatures limit the efficiency and duration of exercise, while heat production from exercise raises body temperature, which further compromises exercise and work capacity, especially in warm environments. Deviations in air temperature with and without the occurrence of exercise are likely to be key factors that compromise physiological responses to toxic agents. Speakers are from fields that address the effects of environmental and exercise stress on a range of salient physiological topics including cellular/molecular biomarkers, pulmonary function, cardiovascular function, thermoregulation, and epidemiological studies on human health and mortality. Participants will emphasize the need for future studies on the interactions between environmental physiology and physiological response to toxic agents.

Physiology InFocus: Neurotransmitters in Cardiovascular Regulation: Glutamate
Chair: F.J. Gordon

The simple amino acid L-glutamate is perhaps the most ubiquitous, fast excitatory neurotransmitter in the central nervous system. It has been more than 20 years since a functional role for L-glutamate as a neurotransmitter of central cardiovascular regulation was first proposed. Since then, studies of central autonomic regulation have been prominent in establishing the significance of glutamatergic neural transmission in mediating integrated physiological responses produced by the brain and spinal cord. Speakers will trace the development of this research area, present experimental results contributing to our current understanding of glutamatergic mechanisms, and address new and emerging concepts that will be important for future research.

Potassium Channels that Regulate Vascular Tone: Which are the Major Players?
Chairs: D. Gutterman and J. Hume

Endothelium-derived hyperpolarization factor (EDHF) plays an active role in vasomotor responses primarily in smaller resistance arteries. EDHF-mediated dilation involves the opening of potassium channels in the sarcolemmal membrane of vascular smooth muscle cells and endothelial cells. With a variety of pharmacological, electrophysiological, and molecular tools for interrogating potassium channel function and structure, we are able to understand better the various properties of potassium channels and mechanisms of vasodilation to stimuli such as hypoxia, ischemia, pharmacological agents, and mechanical stimuli including, shear and myogenic responses. As our understanding of hyperpolarization-mediated dilation increases, however, the complexity of the potassium channel involvement increases as well. This symposium will provide an overview of potassium channel structure, highlight novel observations regarding the role of potassium channels in regulating vascular function, and offer insights into the effects of disease on K-channel activity as it relates to altered vasomotor function. The focus will be on three major classes of vascular potassium channels: calcium-activated potassium channels, ATP-sensitive potassium channels, and voltage-dependent potassium channels.

Physiology, Pathophysiology, and Genetics of Body Weight/Adiposity Regulation
Chairs: P. Havel and B. Horwitz

With its increasing prevalence, obesity has become a major and costly medical problem primarily due to related cardiovascular disease and type 2 diabetes. This symposium will discuss the afferent, central, and efferent pathways by which body adiposity is regulated and will present examples in which obesity results from dysregulation of these pathways. Numerous neural and humoral signals from the gastrointestinal tract, pancreas, liver, and adipose tissue convey to the central nervous system (CNS) afferent information about recent energy intake, as well as peripheral energy stores. Among these are insulin and leptin, which act as long-term signals to the brain and regulate energy balance such that under free-feeding conditions body weight/adiposity are maintained within a relatively narrow range. Both insulin and leptin influence the activity of hypothalamic circuits involving signaling molecules such as neuropeptide-Y, melanocortins (a-MSH), and endogenous melanocortin receptor antagonist (agouti-related protein), melanocyte concentrating hormone, cocaine, and amphetamine related transcript and the orexins, such that energy intake is matched to energy expenditure over time. Energy expenditure and nutrient fluxes are regulated by sympathetic neural pathways via activation of adrenergic receptors and at least in some cases of mitochondrial uncoupling proteins. These autonomic pathways are influenced by the same neuropeptide-containing circuits that regulate food intake. In turn, these can influence metabolic fluxes (nutrient partitioning) between the liver, muscle, and adipose tissue. This can potentially affect insulin secretion and action. Dysregulation of afferent, central, or efferent pathways involved in the control of body weight/adiposity can lead to the mismatches between energy intake and energy expenditure that cause obesity. For example, mutations of genes encoding leptin or the leptin receptor, the melanocortin precursor POMC or CNS melanocorin receptors each lead to hyperphagia and massive obesity in humans as well as in rodents. A detailed understanding of the physiology, pathophysiology, and genetics of these regulatory systems is critical for the development of new approaches for treating obesity and its sequelae.

Lung Surfactant and Reactive Oxygen/Nitrogen Species: Antimicrobial Activity and Host/Pathogen Interactions within the Lung
Chair: J. Hickman-Davis

The respiratory tract is exposed to a multitude of toxic and infectious agents on a regular basis and yet disease is a relatively rare event in the healthy lung. Innate immunity of the lung includes ciliary (mechanical) clearance, cough reflex, and cellular mechanisms. Within the alveolar lining, fluid surfactant proteins provide a first line of defense against invading organisms before the development of specific immunity. Surfactant proteins SP-A and SP-D are hybrid molecules termed collectins that belong to the Ca2+-dependent animal lectin superfamily. The collectins are ideally suited to the role of first line defense in that they are widely distributed within the lung capable of antigen recognition and can discern self versus non-self. These proteins recognize bacteria fungi and viruses by binding mannose and N-acetylglucosamine residues on microbial cell walls. SP-A and SP-D have been shown to stimulate the respiratory burst, as well as nitric oxide synthase expression by alveolar macrophages. Superoxide produced by the membrane bound NADPH-oxidase of macrophages combines with nitric oxide (.NO) to form the oxidant peroxynitrite at near the diffusion limit for these two molecules. Although .NO is a well-recognized microbicidal molecule of macrophages, the mechanism(s) by which NO contributes to host defense remain undefined. .NO may have a direct microbicidal effect through: 1) reaction with iron or thiol groups on proteins forming iron-nitrosyl complexes that inactivate enzymes important in DNA replication or mitochondrial respiration; 2) formation of such reactive oxidant species as peroxynitrite; 3) interaction with the hydroxyl radical (.OH) to induce double strand DNA breakage; or 4) inhibition of antioxidant metalloenzymes such as catalane thereby increasing hydrogen peroxide (H2O2) and .OH concentrations. In general, the understanding of pulmonary host defense mechanisms lags behind that of other systems. Because of the poor accessibility and importance in defense against bacterial infections, it may be possible to develop practical therapies or to increase the lungs protective capacity though a better understanding of the role of surfactant proteins and reactive oxygen and nitrogen species in the early immune response.

Adaptive Regulation of Epithelial Solute Transporters
Chairs: B.H. Hirst and R.P. Ferraris

The molecular identification of membrane proteins involved in transcellular assimilation of organic solutes, such as those involved in macro- and micro-nutrient transport in the gut, enables the investigation of adaptive regulation of these transport systems at the molecular level. Thus, transcriptional as well as post-transcriptional and post-translational mechanisms may now be defined. These studies, although at an early stage, are ripe for discussion. The symposium will illustrate adaptive regulation, in particular, in response to substrate availability of a variety of transport systems. Although focus is on the gastrointestinal (including hepatic) system, lessons extend into all epithelial systems and beyond where nutrient transport and its regulation are issues.

Physiological Genomics: Activity-sensitive Gene Regulation in Muscle
Chair: D.A. Hood

Microarrays are relatively new molecular techniques that can be used to assay for the differential expression of thousands of mRNAs at the same time. In addition, microarrays provide an unbiased examination of mRNAs. Previiously, the investigator selected the specific mRNAs based on bias of previous results, whereas microarrays made with thousands of mRNAs provide unplanned comparisons. Further, these unplanned comparisons not only led to unexpected results, but these findings provide the foundation for previously not-thought of hypotheses. This symposium will synthesize the existing state-of-the-art in microarray analysis concerning the responses of mRNAs to alterations in mechanical and contractile activity on muscle. Researchers have used microarrays to exam alterations in mRNAs following increases in mechanical load. By applying a highly uniform biaxial cyclic strain to cultured smooth and cardiac muscle cells, one scientist used DNA microarray technology to describe the transcriptional profile of mechanically induced genes. Likewise delineation of the molecular response to altered loading of skeletal muscle is unknown. Another used microarray technology to identify mRNAs changing in response to a bout of weight lifting by rats. Previous studies had shown that this model led to skeletal muscle hypertrophy. Altered mRNA expression after removing weight bearing from the soleus muscle has been examined. It is a model that not only induces skeletal muscle atrophy, but that also changes the profile of genes associated with cardiovascular diseases. Also discussed will be a microarray analysis of the differential mRNA expression between two fiber types of skeletal muscle and future uses of microarray in physiological genomics.

Structure and Gating of Epithelial Ion Channels
Chair: T.R. Kleyman

Epithelial cell layers have discrete plasma membrane domains that allow for the vectorial transport of solutes between the lumen (for external environment) and the interstitial space (internal environment). Apical plasma membrane ion channels have key roles in the transepithelial secretion of Cl and K and in the transepithelial reabsorption of Na. This symposium brings together investigators whose work has focused on the structure and gating of three epithelial ion channels; CFTR, ROMK, and ENaC. These channels have critical roles in fluid secretion and in extracellular fluid volume and K homeostasis. Participants will discuss the structure of the CFTR pore and regulation of CFTR gating, the role of the ROMK pore in K channel gating, regulation of ENaC gating, and the structure of the ENaC pore and its role in channel gating.

Effect of Changes in Blood Pressure on Renal Transporters
Chair: A. McDonough

We have recognized for decades that regulation of sodium transport is critical for the maintenance of normal extracellular volume and blood pressure and that renal function is altered in hypertension. Alterations fall into two categories: those responsible for the hypertension (such as elevated sodium transport in the cortical collecting duct) and homeostatic compensations important to match sodium output to sodium intake. Regarding the latter, the phenomenon whereby an increase in arterial pressure provokes an increase in sodium excretion, is known as pressure-natriuresis. In human hypertension, as in all genetic rat models of hypertension, the homeostatic set point is elevated and the pressure-natriuresis response is blunted. Since this response can occur in the absence of a change in GFR, it involves a decrease in net tubular sodium reabsorption. Until recently, very little was understood about the cellular mechanisms responsible for the natriuresis during acute or chronic hypertension. We now know that acute hypertension provokes sodium transporter internalization from the apical brush border and sodium pump inhibition and that chronic hypertension can lead to decreases in sodium transporter abundance. Using recent studies, speakers will address the molecular mechanisms responsible for sensing changes in blood pressure and adjusting renal sodium transport accordingly.

Genetic Modification of Calcium Handling Proteins in Heart Disease: Insights, Roadblocks, and Potential Therapies
Chair: J.M. Metzger

Participants will focus on the mysteries of cardiac EC coupling and sarcomere function in health and disease. The control of sarcomere function begins with Ca²⁺-mediated regulatory events and ends with a chemomechanical transduction event involving the docking of the molecular motor myosin on actin. When considering the multitude of proteins involved and their unique assembly, one can appreciate that the control and regulation of sarcomeric function represents one of the most elaborate intracellular signaling pathways in biology. A growing arsenal of genetic-based tools in concert with technological advances in functional assays offer new opportunities to understand sarcomere function at the cellular tissue and whole-organ levels. Presenters will highlight these advances, including recent studies using transgenesis mutagenesis, gene targeting, and viral-based somatic cell gene transfer to reveal some of the long-held secrets of cardiac EC coupling and sarcomere function in normal and failing hearts. Speakers will also illuminate new therapeutic approaches to systematically modify heart function under (patho) physiological conditions in vivo.

Genomics and Molecular Basis of Exercise and Environmental Physiology: Molecular Control of Thermogenesis
Chair: P.D. Neufer

Thermogenesis, by definition, is the use of energy to produce heat within an organism. For many types of animals, survival in the cold requires the regulation of thermogenesis. In humans, control of thermogenesis is believed to be an important determinant of basal metabolic rate and overall metabolic balance. Speakers will review the current state of knowledge regarding factors that may be controlling thermogenesis and metabolic rate in humans at the cellular and molecular levels. They will also present evidence suggesting that AMPK activity may play a role in sensing metabolic demand with the cell.

How Does the Brain Understand Muscle Mechanics?
Chairs: T.R. Nichols and J.C. Houk

Coordinated movement in biological organisms has resulted from the co-evolution of the musculoskeletal and central nervous systems. The phylogenetic relationship between these two systems suggests that the organization and dynamic properties of neural circuits reflect the structure and kinetic properties of the musculoskeletal system, as well as the mechanical constraints imposed by the environment. The growing interdisciplinary nature of physiological research has provided an environment in which the study of interactions between neural and muscular systems can flourish. Contemporary research in motor systems has provided new insights into these interactions and how musculoskeletal organization is represented centrally. The manner in which these two physiological systems bring about coordinated movement is the subject of this symposium. Presenters will review previous contributions to the neuro-mechanical basis of movement and more recent work on the regulation of posture by circuits in the spinal cord; discuss the way cellular properties of motoneurons complement the mechanical properties of muscle units; address the control of the digits in primates in terms of the appropriate muscular organization and cortical organization; discuss the physical problems of multijoint coordination and the way this coordination is brought about by cortical mechanisms; and present models of central mechanisms and muscular dynamics that have been designed to explain the control of reaching and grasping. Controversial issues, such as the existence of internal models and maps, will be discussed as well as new approaches, both methodological and theoretical, that will be required to advance this field.

Interplay Between Nitric Oxide and Hemoglobin: Current Concepts
Chairs: R.P. Patel and M.B. Grisham

The role of nitric oxide (NO) in numerous physiological and pathological processes is widely documented. Compelling evidence indicates that under physiological conditions, NO has key functions in maintaining vascular homeostasis and preventing vascular injury. However, our knowledge regarding how NO function is regulated in the vascular compartment remains poorly defined. Elucidating these key issues will offer insights into the mechanisms that lead to vascular injury during diseases (e.g., atherosclerosis) or damage incurred during ischemia-reperfusion injury. Speakers will focus on a specific area of regulation of NO biology involving reactions with hemoglobin (Hb). Early thinking was that NO reactions with erythrocytic Hb are restricted to the proteins heme groups and that this represented a safe route to detoxify and remove NO produced from the endothelium. Recent studies suggest, however, that NO reactions with circulating red blood cells are more complex than previously thought. The hypothesis is that Hb regulates NO function in vivo. The interactions between NO and Hb must also be understood an Hb-based blood substitute is going to be beneficial in the clinic. Speakers will review Hb and NO biochemistry and how this affects vascular function both under physiological conditions of blood flow and when cell free Hb is introduced into the system; present seminal observations that have led to the controversial hypothesis that Hb modulates blood flow via the intermediate formation of S-nitroso-Hemoglobin, a novel derivative in which a specific cysteine residue on the ß-chain (ß93Cys) is nitrosolated; address the effects of S-nitrosation of Hb on the vascular functions of NO; discuss the effect the red blood cell has on Hb-NO interactions; and present the insights gained from specific amino acid mutations on reactions of NO with Hb.

Nutritional Neuroscience
Chairs: L. Lima and L. Cintra

The symposium will cover some aspects concerning the influence of nutrition on physiological functions of the central nervous system. Speakers will consider the organization of the circadian rhythmicity and the suprachiasmatic nuclei and rehabilitation of CA3 hippocampal pyramidal cells in malnourished rats; the effect of mild protein prenatal malnutrition, the release of noradrenaline, and the density of neurons in the rat cortex; spreading depression in rats submitted to short periods of malnutrition during lactation period; the influence of micronutrients such as taurine during development and regeneration of the central nervous system; and the neurobiology of food, mood, and health.

Mitochondria and Energy Metabolism in Heart Failure, Hypertrophy, and Remodeling
Chair: M.A. Portman

Mitochondria appear to initiate the complex signaling cascades that promote apoptosis and cell death, reinvigorating interest in mitochondrial integrity and function over the past year. Furthermore, mitochondria also seem to be significant in myocardial remodeling during heart failure and hypertrophy. During heart failure, patterns of gene and protein expression, as well as substrate preference and high-energy phosphate kinetics, resemble those apparent in the developing heart. Participants will review recent findings and issues related to mitochondria function during development hypertrophy and remodeling.

Intermittent Hypoxia: Cell to System
Chairs: N.R. Prabhakar and E.C. Fletcher

Intermittent hypoxia (IH) is an intriguing pathophysiological situation associated with many clinical conditions, including sleep apneas, apneas in premature infants, and lung diseases (e.g., COPD asthma pulmonary fibrosis). IH has long-term effects on the cardio-respiratory systems, which lead to hypertension and ventilatory abnormalities in humans and experimental animals. Studies have begun addressing the effect of IH on cellular processes. Emerging evidence suggests that IH is a more potent stimulus for activating gene expression than sustained hypoxia. Proteins encoded by the genes might contribute to cardio-respiratory abnormalities associated with IH. This session will bring together scientists that work on molecular mechanisms, as well as cardio-respiratory responses to IH in experimental animals, as well as humans. Speakers will discuss the fundamental mechanisms of gene expression and second messenger changes in neuronal cells in response to cyclical stimuli and how they differ from sustained stimulus; present evidence for the involvement of distinct cellular mechanisms associated with gene expression by IH in isolated cells and intact animals; dwell on the effect of IH on the respiratory system, emphasizing the role of spinal protein synthesis in respiratory plasticity induced by IH; and deal with cardio-respiratory responses to IH in humans and in experimental animals and the potential mechanisms contributing to these alterations. Given the potential clinical implications of IH, we hope that this symposium provides impetus for further progress in this emerging area.

The Role of the Cell Membrane in Regulating Excitability and Contractility During Exercise and Fatigue
Chairs: J-M. Renaud and T. Nosek

During exercise, muscles must maintain their membrane excitability, which is accomplished mainly by activating the Na+ K+ pump. However, when the amount of energy (i.e., ATP levels) in muscle fibers starts to decrease, then the K+(ATP) channels become activated and reduce membrane excitability. This then reduces the amount of calcium released by the sarcoplasmic reticulum and eventually forces development in order to reduce ATP utilization. A decrease in ATP levels may also reduce the activity of the L-type calcium channels, which are not only ATP sensitive but also are involved in the signaling between the action potential and calcium release. Thus, the cell membrane plays important roles during exercise. It must maintain its own excitability in order to maximize muscle performance until the energy reserves start to be depleted. At that point, the reverse must occur and membrane excitability must decrease. Presenters will discuss how the cell membrane plays such crucial roles during exercise and fatigue development.

Mechanical Modulation of Gene Expression in the Musculoskeletal System: From Nucleus to Organism
Chair: C. Rubin

The mass and morphology of the muscloskeletal system is strongly influenced by mechanical stimuli. At the organismal level, there is much experimental evidence that demonstrates that removal of function will lead to disorders such as sarcopenia and osteopenia while brief exposure to specific parameters within the mechanical milieu can be strongly anabolic. Clearly a better understanding of the molecular mechanisms that control the balance between form and function in the musculoskeletal system may lead to new interventions for the acceleration of fracture healing, the promotion of osseointegration, the inhibition of osteoarthritis, and the reversal of osteoporosis. In this session, speakers will examine the mechanical sensitivity of various cells and tissues within the musculoskeletal system in a hierarchical fashion with the goal of demonstrating that even small mechanical stimuli can result in massive changes in cell, tissue, and organ morphology.

Renal and Comparative Physiology of Urea Transporters
Chairs: J.M. Sands and M.A. Knepper

Urea transporters are important players in the urine-concentrating mechanism. Several facilitated urea transporters have been cloned from mammalian kidney and from erythrocytes, raising the intriguing question as to why the kidneys need so many urea transporters. Urea transporters have also been cloned from elasmobranchs and amphibian species. Their conservation through evolution suggests that they play an important physiologic role. Symposium speakers address various aspects of the regulation of urea transporters in the mammalian kidney and in other species, since an understanding of the comparative and evolutionary aspects of urea transporters may help us understand their role in renal function. Participants will specifically discuss the genetic organization of the UT-A urea transporter family and transcriptional control of its various isoforms; the intra-renal localization of the UT-A protein isoforms and the regulating of these proteins; the role of urea in permitting the inner medulla to adapt to osmotic stress; the comparative physiology of urea transporters, including the cloning of UT-A-like urea transporters in elasmobranches and evolution of urea transporters and urea cycle enzymes.

Genomics and Molecular Basis of Exercise and Environmental Physiology: Molecular Response to Hypoxia
Chair: L. Sonna

How do cells respond to hypoxic stress (e.g., which can occur at high altitude)? Presenter will review three lines of investigation: hypoxia-inducible factor-1 (the first transcriptional factor shown to be induced by hypoxia); the heme-oxygenase system, which is induced in many tissues in response to hypoxia; and the sodium transport systems of lung, which may play a role in high-altitude pulmonary edema. In addition, there will be a review of the effects of hypoxia on nitric oxide synthase.

Engineering Islet Cells for Cell Therapy of Diabetes Mellitus
Chairs: B. Soria and C.B. Newgard

Pancreatic islets are neuroendorcrine organs that control blood glucose homeostasis. The precise interplay of a heterogeneous group of cell populations (ß, a.d, and PP cells) results in a fine-tuned release of counterbalanced hormones (insulin, glucagon, somotostatin, and pancreatic polypeptide). Under the premises of a detailed knowledge of the physiological basis underlying this behavior, we might infer two lines of work: generating computational and operational models to explain and predict this behavior and engineering islet cells to reconstruct pancreatic endocrine function. Whereas the former is fueled by new computational strategies, which give physiologists the possibility to model a system in which new "emergent" properties appear, the latter benefits from the useful tools and strategic knowledge achieved by molecular, cell, and developmental biologists. This includes using tumor cell lines, engineering islet cell precursors, differentiation, regeneration and growth, and, finally, therapeutic cloning of human tissues. Gaining deep physiological understanding of the basis governing these processes is instrumental in order to engineer new pancreatic islets.

Model Organisms: Functional Genomics of Membrane Transport
Chair: K. Strange

"Functional genomics" is defined as the assignment of function to identified genes and, importantly, the elucidation of the organization, integration, and control of gene networks that give rise to specific physiological processes. It is widely recognized that the intellectual and technical challenges posed by attempts to define the genetic basis of physiology necessitate the study of less complex "model organisms." Speakers will describe the use of yeast, Caenorhabditis elegans, and Drosophila melanogaster in order to characterize the physiological functions, regulation, and structural aspects of ion channels and transporters.

Bioinformatics in Biology and Engineering
Chairs: S. Subrmaniam and J. Bassingthwaite

In the past decade, we have witnessed a large paradigm shift in biology. The ability to study biological systems at microscopic scales in finer levels of detail has provided a wealth of information about the complexity underlying biological phenomena. In addition, the advent of the genome projects has fundamentally transformed biology into an information-driven science. There are two emergent themes from this revolution: first, complexity is the hallmark of biological systems and second, the coupling between size and time scales of biological phenomena are not hierarchical. These themes challenge us to link the microscopic and macroscopic descriptions of biology. The genome of an organism provides the blueprints for its life and functioning. Deciphering how this blueprint is implemented complex and involves a new version of the central dogma in which the genome contains the code for gene products that induce physiological functioning through couplings and interactions among themselves and surroundings. This has serious implications for the macroscopic picture of physiology. Information on all the codes and mechanisms by which the code functions is accessible to modern biochemical and biophysical measurements. The task of decoding this information is arguably the biggest challenge faced by modern biology. Even for the simplest prokaryotic cell, the genome is tens to hundreds of million base pairs long. Small changes in the genome are responsible for variant function (such as altered metabolism). Detecting and processing this polymorphism is fundamentally important to biology and medicine. This session will focus on areas between the crossroads of biology informatics and engineering.

Russian and Eastern-Block Physiologist: Recognition Because of Pre-World War II and Cold War Conditions
Chairs: C.M. Tipton and G.E. Folk, Jr.

Presenters hope to "educate and remind" the APS membership of select and important scientific contributions made by Russian physiologists from pre-World War II to after the Cold War. The rationale is that the lack of recognition citation or familiarity with various Russian accomplishments occurred in part because political conditions between the United States and Russia during that period did not facilitate scientific interactions or informational exchanges. The areas of physiology that appear to be most affected by these circumstances are the ones (exercise and endocrinology) that encompass stress physiology. Consequently, the renowned scholar of exercise endocrinology, Atko Viru, from the University of Tartu in Estonia has been invited to be a featured speaker on this specific subject, using his personal and professional knowledge of Russian scientists in this area. A tangential area related to the topic of Viru is the role of the sympathetic nervous system in the prevention of muscular fatigue. Ronal Victor from Southwestern Medical School is to discuss select Russian physiologists, whose findings are generally unknown by current investigators and authors. Despite token efforts by both countries to promote scientific interactions, political ideologies inhibited open exchanges between space scientists. Sjoerd Bonting of the University of Nijmegen in the Netherlands, who had intimate knowledge of the Russian space program, will address this aspect as it related to individual Russian space scientists.

Protein-Protein Interactions in Signal Transduction
Chairs: E.J. Weinman and S. Shenolikar

Emerging evidence indicates that the localization and function of many membrane proteins rely on the assembly of multiprotein complexes that link these plasma membrane proteins to the underlying cytoskeleton. Recent studies make a compelling argument in favor of multiprotein complexes in the physiological regulation of ion transporters in renal and other epithelial tissues. Such studies demonstrate a key role for PDZ-domain containing adapter proteins in the hormonal regulation of several renal ion transporters. Further work has expanded the role for the protein adapters to the targeting, trafficking, or sorting of G-protein-coupled receptors and signal transduction by receptor tyrosine kinases and other signaling molecules. This symposium will review the function and organization of signaling complexes in polarized cells and emphasize the importance of adapter proteins in bringing together signaling proteins and their substrates and thereby imposing the remarkable specificity of signal transduction in neurons and epithelial cells.

Life, Sex, and Death: The Physiological Basis of Life-History Traits and Trade-Offs
Chairs: T.D. Williams and B. Sinervo

Fisher, a doyen of evolutionary biology, was the first to point out the importance of the connection between physiological mechaniam and life history. It has been said that "physiology contributes insight into the mechanisms that cause trade-offs" and that "physiological trade-offs are involved in almost all micro-evolutionary trade-offs." Despite this recognition of the importance of considering physiology in life-history studies, the physiological basis of most if not all trade-offs remains unknown. Indeed, much current life-history theory is divorced from physiology and other components of organismal biology. The development of the field of "evolutionary physiology" has led to significant and very productive integration of physiology and evolutionary biology. To date, however, much of this work has focused on performance-related traits (e.g., sprint speed, maximum sustainable metabolic rate) rather than life-history traits per se. Stearns provided an "incomplete" trade-off matrix for ten life-history traits, i.e., 45 life-history trade-offs. He pointed out that only five of these had received much attention and most of this from ecological or evolutionary studies. This symposium will provide a state-of-the-art look at this issue. Talks will cover a wide range of life history traits: offspring size and number, future versus current reproduction growth versus subsequent condition, and survival and reproductive maturity versus life span and aging. The symposium will also be taxonomically broad, with talks on insects, fish, reptiles, birds, and mammals. Each speaker will summarize the current state of our knowledge on the mechanistic basis of the major life history and highlight important areas for future research.

Metabolic Complications in HIV/AIDS
Chair: K. Yarasheski

Recent data highlight the complexities involved in understanding and managing the constellation of alterations in fat distribution and glucose and lipid metabolism that have occurred in the current treatment era. Although there is ample evidence that protease inhibitors play a role in the development of some of these alterations, current data suggest a role for nucleoside analogue, reverse transcriptase inhibitors as well. In addition, factors such as age, body mass index, gender, race, duration of HIV infection, and effective viral suppression may also modulate the risk of developing fat distribution and metabolic abnormalities. Current prevalence estimates vary, and the interrelationships among the metabolic and fat distribution abnormalities have not been defined. In addition, the etiology specific sites of dysregulation clinical sequelae and effective management strategies for these alterations remain to be identified.

	Tutorials

TOP INTRODUCTION The American Physiological... Tutorials Workshop American Society for... Special Sessions Satellite Meetings American Society for... American Society for... Focus groups/workshops Course Career Development American Society for Nutritional... The American Association of... Special Symposia 2001 FASEB Excellence in... Presidential Symposium Presidential Address Distinguished Lecturers Workshop American Association of...

 
Tissue Engineering: Opportunities and Challenges
Chair: R.M. Nerem

Tissue engineering is an emerging technology that represents the next generation of medical implants. The goal is to create biological substitutes and/or foster tissue regeneration in order to replace, repair, maintain, or enhance tissue/organ function. Although a fledgling industry today, it has the potential to reach more than $50 billion annually. To realize this potential, enabling core technologies must be developed. These range from cell technology to an integrative biologic system, which can best be addressed by multidisciplinary teams. Participants will examine the challenges presented by tissue engineering, highlighting future opportunities for those in the life sciences and biomedical engineering.

Experimental Gene Delivery and Therapy
Chairs: C.H. Gelband and C.D. Sigmund

The area of gene therapy and/or transfer is one that is expanding tremendously. Gene therapy is being used both clinically and experimentally for treating diseases of numerous different physiological systems. These include diseases of, but are not limited to the cardiovascular system, nervous system, lung, and gastrointestinal tract. In this workshop, speakers will present an review the use of gene therapy tools; the use of gene therapy to treat lung disorders including cystic fibrosis; focus on gene delivery and therapy for ischemia/reperfusion injury; gene therapy tools for blood disorders; and gene therapy for muscular disorders.

	Workshop

TOP INTRODUCTION The American Physiological... Tutorials Workshop American Society for... Special Sessions Satellite Meetings American Society for... American Society for... Focus groups/workshops Course Career Development American Society for Nutritional... The American Association of... Special Symposia 2001 FASEB Excellence in... Presidential Symposium Presidential Address Distinguished Lecturers Workshop American Association of...

 
Integrative Approaches for the Study of Physiological Function in Genetically Altered Mice
Chairs: J.N. Lorenz and D.L. Mattson

The availability of genetically altered mouse models has led to the development of a wide variety of in vitro and in vivo methodologies for studying the functional consequences of specific gene alterations. Over recent years symposia on cardiovascular techniques for specific use in the mouse have become rather commonplace at scientific meetings, and as a result, many laboratories have begun to incorporate these methodologies into their arsenal of techniques. Whereas there has been much attention to the study of cardiovascular function in mice (blood pressure, cardiac output, left ventricular performance), there has been less afforded the study of other organ systems or of integrated function. Participants will discuss integrative techniques for evaluating functional phenotype in a wider variety of organ systems, for which useful mouse models already exist. Speakers will also discuss advances in the study of GI physiology in the mouse; techniques in the study of pulmonary physiology and lung mechanics in the intact mouse; approaches to evaluate metabolism and integrative cardiovascular function in the mouse; and the biological application of chip-based microelectromechanical systems (BioMEMS) to physiological study. In addition, there will be a review of some of the current techniques used to study cardiovascular and renal physiology in the mouse.

	American Society for Biochemistry and Molecular Biology

TOP INTRODUCTION The American Physiological... Tutorials Workshop American Society for... Special Sessions Satellite Meetings American Society for... American Society for... Focus groups/workshops Course Career Development American Society for Nutritional... The American Association of... Special Symposia 2001 FASEB Excellence in... Presidential Symposium Presidential Address Distinguished Lecturers Workshop American Association of...

 
Symposia
THEME I: Biological Signaling Networks
Phosphoinositide Signaling
Chair: A. Toker

Phosphoinositides, minor membrane phospholipids found in all eukaryotic cells, serve as critical mediators of many agonist-stimulated signal transduction pathways. These control cell growth, death, and differentiation. Intense research in the past two decades has elucidated both the regulation of these lipids by phosphoinositide kinases and phosphatases, as well as their mode of action. In particular, binding of various phosphoinositides to target proteins has been shown to alter their activities and/or cellular location. Deregulation of phosphoinositide signaling has also been directly linked to human diseases such as cancer and diabetes. Speakers will highlight recent advances in phosphoinositide signaling, and emphasize the phosphoinositide 3-kinase and phosphoinositide phosphate kinase pathways. They will also present technical advances for studying phosphoinositide signaling.

THEME II: Molecular Basis of Cell and Developmental Biology
Vesicular Organization/Trafficking
Chair: S.D. Emr

Protein transport in the secretory and endocytic pathways is mediated by small vesicle carriers that bud from a donor organelle and then dock and fuse with the appropriate acceptor organelle.

Membrane and lumenal proteins are incorporated into the transport vesicles through direct or indirect interactions with coat proteins assembled on the cytoplasmic surface of the donor membrane. After transport to the correct target membrane, the transport vesicle docks with the membrane through a cascade of molecular interactions that includes the binding of membrane proteins on the vesicle (termed v-SNARES) with membrane proteins on the target membrane (termed t-SNARES). Formation of the v- and t-SNARE complex is followed by the fusion event that completes the transport reaction. Vesicle trafficking is a highly regulated process. Both proteins like Rab GTPases and lipids like polyphosphoinositides (PIs) participate in this regulation. Speakers will discuss recent advances made in membrane transport and the formation of transport intermediates. In addition, the specific role played by the core machinery for vesicle docking and fusion and the regulation of these events by Rab proteins and PIs will be presented.

Cell Cycle
Chair: F. Cross

The eukaryotic cell cycle is regulated by highly conserved machinery that ensures efficient, robust, and error-free duplication and segregation of chromosomes into daughter cells. Speakers will consider different approaches to studying cell cycle regulation, ranging from genetics and cell biology to computer modeling.

Apoptosis
Chair: V.M. Dixit

Apoptosis, or programmed cell death, is a fundamentally important process that maintains tissue homeostasis in multicellular animals. Disorders of apoptosis contribute to many human diseases including cancer. Participants will discuss recent advances in the identification and characterization of molecular components of the pathway including its initiators, regulators, and terminal effectors.

Extracellular Communication/Integrins
Chair: M.H. Ginsberg

Integrins, preeminent cellular receptors for adhesion to the extracellular matrix in multicellular animals, play pivotal roles in a wide variety of processes involving cell migration and cell-cell interactions. Integrin signaling controls programs of gene expression, cell growth, and cell survival. The signaling functions of integrins are an important complement to their mechanical roles as adhesion receptors. Furthermore, cells can regulate the function of integrins by changing their affinity for extracellular ligands. Thus, integrins exemplify paradigms of bi-directional communication between the extracellular milieu and the cell interior. Participants will report on recent advances in the transmission of information via integrins, including analysis of the structural basis of integrin activation, how integrin signals are transduced into cells, and the reciprocal cross talk between integrins and small GTPases of the Rho and Ras families.

Glycobiology
Chairs: H. Schachter and A.J. Parodi

As conspicuous components of the external cell surface, protein-linked oligosaccharides play a fundamental role in recognizing phenomena involved in cell differentiation, organogenesis, and development, and pathogenesis. Participants will discuss the 3-dimensional structure of an enzyme (trans-sialidase) located on the outer surface of a parasitic protozoon plasma membrane; describe work showing that Fringe is a beta-1,3-N-acetylglucosaminyltransferase that acts on O-linked fucose residues on the membrane receptor Notch; review evidence from humans and mice showing that complex N-glycans are essential for normal embryogenesis and development; and discuss recent work showing that complex N-glycans might play a similar role in the soil nematode Caenorhabditis elegans.

THEME III: Functional Genomics/Gene Expression
Proteomics/Genomics
Chair: D. Eisenberg

Using what is often called the post-genomic paradigm for research in molecular biology, biologists are increasingly able to study the structure, function, and interaction of many cellular components at once. These new approaches are the result of increased automation and computerization, the availability of fully sequenced genomes, and of new concepts of the meaning of macromolecular function. Protein function in its postgenomic sense can be defined as the context of interactions of a molecule in its several cellular roles. Diverse approaches to postgenomic biochemistry and molecular biology will be discussed. Specifically, speakers will describe the power of DNA microarrays in revealing cellular interactions; discuss the application of structural genomics to the study of structure on a genome wide scale; and present new computational tools for analyzing protein-protein interactions.

Structural and Functional Genomics of Signal Transduction
Chair: K.S. Shokat

Proteins that transfer structural information about growth factors, cell cycle status, cytoskelatal organization and other cellular processes are abundant in the human genome. Spekers will focus on new methods for dissecting the functions of these proteins (both experimental and computational). Topics will include small molecule drug design, chemical genetics, protein phosphorylation cascades in prokaryotes, and eukaryotes. Genome-wide approaches to signal transduction research and bioinformatics approaches to decoding signal transduction networks will be emphasized.

Chromatin Remodeling Factors
Chair: J.L. Workman

It is increasingly clear that pathways of transcription regulation in eukaryotes exploit the structural proteins that package DNA into chromatin. Several transcriptional regulators have been found to function at least in part by modifying chromatin. This includes previously identified protein complexes such as general transcription factors and novel protein complexes identified by genetic screens or by their activity in modifying chromatin in vitro. This session will cover topics concerning the function of chromatin in the regulation of transcription and other nuclear processes. Speakers will cover the intimate link between the function of transcriptional co-activators and histone modifications; the functions of ATP-dependent chromatin remodeling factors, which can participate in gene activation or repression; and the functions of transcriptional repressors that participate in the epigenetic control of gene expression.

RNA Polymerase
Chair: J.W. Conaway

Messenger RNA synthesis is a major site for the regulation of gene expression. Recently, the development of methods for obtaining crystal structures of RNA polymerases and their complexes has ushered in a new era in studies of transcriptional regulation and has revealed fundamental features of the mechanisms of messenger RNA synthesis at atomic resolution. The combination of electron microscopic and high-resolution cross-linking techniques has brought to light novel features of the topology of RNA polymerase transcription complexes and yielded key insights into the dynamic structural changes that accompany the transition of polymerases from the initiation to the elongation stages of transcription. In addition, continuing biochemical studies are leading to the discovery of novel transcription factors that function to control the activity of RNA polymerases by unprecedented mechanisms. Participants will discuss highlights of these recent advances.

THEME IV: Supra Molecular Structure and Function
Molecular Machines/Motors
Chair: S.M. Block

Recent advances in biophysics, biochemistry, and molecular genetics have shed new light on the fundamental mechanisms by which proteins generate movement. Biological motors that move in a linear fashion not only include the classic mechanoenzymes, such as myosin, dynein, and kinesin, but also processive nucleic acid enzymes, such as polymerases, topoisomerases, and helicases. There are also motors that rotate, such as ATP synthase and the bacterial flagellar motors. There are numerous outstanding questions about molecular motors: For what special purposes are molecular motors used? How is chemical energy transduced by motors into mechanical displacement under load? What confers motor directionality (and how did this evolve)? What kinds of motor (or motor-like) mechanisms exist in nature, and are there any common features? How are cellular motors, and their cargo, controlled, and regulated by cells? Leading researchers in the area of molecular motors will discuss recent experimental progress that has been made toward answering some of these questions. Of particular interest are the interdisciplinary aspects of research in this area, which combines biophysics (including work with optical traps, nanometry, and advanced fluorescence microscopy) with surface science and molecular genetics.

The Ribosome
Chair: J. Frank

The ribosome is a macromolecular machine of high precision that is responsible for the synthesis of proteins following genetic instructions contained on the mRNA. Despite decades of research, the precise mechanisms of such pivotal processes as decoding, peptide bond transfer, and translocation are still not understood. However, recent publications of X-ray structures for the ribosomal subunits of T. thermophilus (30S) and H. marismortui (50S) have moved us closer to this goal. The stage is set for describing the interactions of tRNA and protein factors promoting initiation, elongation, termination, and recycling with the ribosome in atomic detail. In approaches to explore the dynamics of these interactions, and the associated conformational changes of ribosome and protein factors, cryo-electron microscopy has emerged as an indispensable tool.

Nuclear Pore
Chair: M.P. Rout

Nuclear pore complexes (NPCs) are the sole mediators of nucleocytoplasmic exchange and thereby define the contents of the nucleus. NPCs are also one of the characteristic structures of the nuclear envelope, a major organizer site for chromatin. The pivotal role of the NPC in controlling communication between the genetic material and the rest of the cell is reflected in the many oncogenic and developmental defects directly associated with alterations in nucleocytoplasmic transport. A full understanding of how the NPC mediates transport and associates with its neighboring structures is needed to discern the nature of these defects. This requires a comprehensive inventory of the molecular components of the NPC, a knowledge of how each component contributes to the overall structure of this large molecular translocation machine, and information on the interactions its proteins make with components of the soluble phase of nucleocytoplasmic transport, and its structural surroundings. Speakers will focus on proteomic approaches to determining the composition, architecture, and possible transport mechanism of the NPC itself; discuss the interactions made between the NPC and the cargo-carrying transport factors; present new data on the methods by which these factors carry their cargoes across the NPC and how they gain their directional cues, their energy, and how they might be returned for another round of transport; and present recent evidence that implicates proteins that extend from the nuclear face of the NPC deep into the nuclear interior in the organization of silent chromatin and various nuclear processes at the nuclear periphery.

Education Symposia and Workshops
Teaching New Graduate Students to Become TAs
Chairs: J.K Zimmerman and H.B. White, III

Data from NSF indicates that more than 60% of students entering graduate programs in science obtained their undergraduate degrees from smaller, liberal arts colleges. This often means that new graduate students have not been exposed to Teaching Assistants, yet are expected to be proficient in that role. These students, and all other students teaching for the first time, need to be trained. Our session will highlight three, long-running training programs for new teaching assistants, one from a chemistry program (Purdue), one from a biology program (Texas A&M), and one that extends across college lines within a university (Clemson).

Scientists of Color: Diversifying the Profession
Chair: T.D. Landefeld

This session focuses on the problems associated with the diversification of the professoriate, with particular emphasis on faculty in the sciences. Speakers will address the multitude of factors that contribute to this problem at all levels. For example, the recruitment of minority faculty is intricately tied to the successful retention of those faculty members. At the same time, an important component of this problem is the need to expand the pool of students, focusing on K-12 levels but also continuing through the graduate school population. Speakers will discuss their individual experiences and any efforts by their institutions in this area.

Lecture Demonstrations in Biochemistry and Molecular Biology
Chair: H.B. White, III

Lecture demonstrations provide interest, variety, excitement, and involvement to introductory chemistry courses. That tradition has not carried over to biochemistry and molecular biology, where didactic lectures remain standard fare. This symposium will present several examples of lecture demonstrations appropriate for biochemistry and/or molecular biology classes.

Problem-Based Learning
Chair: P. K. Rangachari

To learn is to change. Education abhors the status quo. Education is essentially a political act. Like all political endeavors, chances of success are better with the willing participation of the parties involved. Educational enterprises seek to produce changes in knowledge, skills, or attitudes—preferably all three. Fostering student-centred learning should be the rule rather than the exception. Problem-based learning (PBL) provides one such opportunity. Shorn of all rhetoric, it is designed to encourage participation by plunging students into situations requiring them to define their own learning needs within broad goals set by the teachers. Situations, cases, experimental results, even news items, can be used as springboards for learning. Small groups are not strictly necessary. PBL hopes to meld process and content. Thus what is learned is inextricably linked to how it is learned. An undergraduate science program will be described in detail. With active audience participation, the promises and pitfalls of PBL