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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 the American Association of Anatomists—and by various guest societies. A sampling of the multidisciplinary sessions, listed by host societies, appears below. The abstract issues of The FASEB Journal and the meeting Program contain full details and are mailed to preregistrants before the meeting. For up-to-date information, visit http://www.faseb.org.
The American Physiological Society
Symposia
Cell-cell crosstalk in the generation of inflammation
Chair: J. Bhattacharya
Tissue inflammation, which is fundamental to many pathophysiological conditions, is characterized by leukocyte recruitment at the site of inflammation. In the last 20 years much has been learned regarding specific receptors on leukocytes and on vascular endothelium that subserve leukocyte recruitment and are therefore essential for the inflammatory response. However, relatively little is understood regarding the extent to which intercommunication between different cell types plays a role. Such crosstalk is clearly important since the multicellular nature of the inflammation response predicates that different cell types must signal one another to coordinate endothelial barrier changes and other inflammatory consequences. Crosstalk is also critical for conveying defensive signals across epithelial barriers. Pathogens in the airway or intestinal lumen elicit inflammatory responses, although little is known regarding how pathogen-induced proinflammatory signals translocate across the impermeable epithelial barrier. This symposium will bring together new and exciting research that directly addresses these novel and under-investigated issues. Speakers will discuss crosstalk mechanisms in different systems, highlighting the general nature of this signaling and pointing to new experimental strategies that may be brought to bear in future research. This subject has not been discussed in any meeting, workshop, or symposium.
Translational research in preeclampsia and pregnancy-induced hypertension
Chairs: R. A. Khalil and P. August
Normal pregnancy is often associated with reduction in systemic vascular resistance and arterial blood pressure and decreased vascular reactivity to circulating vasoconstrictors. The hemodynamic and vascular changes observed during normal pregnancy have been explained, in part, by increased nitric oxide (NO) synthesis by various cells including vascular endothelial cells. In 5 to 7% of pregnancies, women develop preeclampsia, a condition characterized by increased intravascular coagulation, proteinuria, increased systemic vascular resistance, and pregnancy-induced hypertension (PIH). Although PIH is a major cause of maternal and fetal mortality, the mechanisms of this disorder have not yet been clearly identified. In addition to performing mechanistic studies in pregnant women, recent research efforts have focused on and have been successful in developing animal models of PIH. These studies have suggested that a reduction in the utero-placental blood flow and the ensuing placental ischemia during late pregnancy is associated with placental release of cytokines, which eventually leads to increased systemic vascular resistance and PIH. However, the cellular events that initiate the placental ischemia and the intermediary vascular and cellular mechanisms that lead to PIH are still unclear. The session will highlight the current issues related to the pathophysiology and the cellular, vascular, renal and endocrine mechanisms of PIH. Participants will focus on abnormal cytotrophoblast invasion of the uterine microcirculation and the ensuing placental ischemia during PIH; the role of placental cytokines in the pathogenesis of PIH; the changes in cardiovascular and renal hemodynamics associated with PIH; endothelial and vascular smooth muscle cell dysfunction in PIH; and the clinical aspects and new approaches in the management of PIH. This multifaceted, cross-sectional session should provide a better understanding of the pathophysiological basis of PIH and should help design better ways to manage this serious pregnancy-associated disorder.
Vascular consequences of oxidant stress
Chairs: B. Pitt and F. Miller
Participants will present the latest information concerning the effects of free radicals and reactive oxygen species on vascular function and biology. The talks will encompass a spectrum of the vascular consequences of free radicals and reactive oxygen species; the cellular sources of free radicals during oxidant stress and disease processes, movement of superoxide and peroxynitrite, both anionic species, through chloride channels; the signaling mechanisms by which reactive oxygen species exert their effects on cellular function and gene expression; the regulation of metabolism by reactive nitrogen species; regulation of oxidant stress by nitric oxide; and the biochemical and biophysical mechanisms by which free radicals and reactive oxygen species modulate protein function.
Mechanism of estrogen effects on the cardiovascular system
Chair: D.R. Gross
The risk of coronary artery disease in women between puberty and menopause is significantly lower than in age-matched men. This gender difference is not found in postmenopausal women. Studies conducted in a man with disruptive mutation in the estrogen-receptor gene showed impaired flow-mediated, endothelium-dependent vasodilation and premature coronary artery disease. Experimental studies have shown that treatment with estrogen can preserve endothelium-dependent coronary artery dilation, reduce infarct size, decrease the occurrence of ventricular arrhythmias, and protect against global, cardioplegia-protected myocardial ischemia-reperfusion injury. This symposium will review the most recent work and characterize the work that remains to be done to more fully describe and understand the mechanisms by which estrogen exerts its effects on the cardiovascular system.
Mechanisms of vascular remodeling: temporal events from stimulus to structural and functional changes
Chairs: M.A. Hill and G. Meininger
The session will focus on the temporal aspects of vascular remodeling. Highlighted will be cell signaling within the vascular wall with emphasis on the events that may link the acute vasomotor responses with longer time frame adaptive responses. Coverage will be given, in particular, to the involvement of cell junctions, matrix-integrin interactions and the cytoskeleton. To broaden the interest in the symposium, input will be drawn from both the smooth muscle and endothelial fields and responses to both agonist and physical stimuli will be considered.
Cardiac fibroblasts and heart failure
Chairs: P.A. Lucchesi and W. Hseuh
The myocardium undergoes a dramatic remodeling in response to hemodynamic stress. Much emphasis has been placed on the role of altered cardiomyocyte function during the progression of heart failure. Recently, a role for cardiac fibroblasts in ventricular remodeling has emerged in studies indicating that mechanical and neurohormonal changes that occur in response to hemodynamic overload exert a profound effect on cardiac fibroblast function. These changes include increased proliferation, secretion of cytokines and neuropeptides, and dynamic regulation of the extracellular matrix through altered synthesis of not only matrix components, but also of enzymes that regulate matrix degradation. Symposium participants will highlight the recent advances made in characterizing altered fibroblast function during the progression of heart failure, including the regulation of fibroblast growth and secretion by mechanical stretch and changes in the neurohormonal milieu and the control of cardiac remodeling and fibrosis by altered fibroblast secretion of extracellular matrix proteins and matrix metalloproteinases.
New paradigms in neovascularization
Chairs: G.C. Schatteman and K. Peters
For many years, two models of new blood vessel growth were used to describe all neovascularization in the embryo and adult. The first, angiogenesis, is described as the sprouting of new blood vessels from existing blood vessels through proliferation and migration of endothelial cells. Vasculogenesis is the coalescence of angioblasts into blood vessels in situ. Angiogenesis was generally considered the only process of neovascularization in the adult, whereas both angiogenesis and vasculogenesis are thought to occur in the embryo. Spawned by the rediscovery of angioblasts in adult peripheral blood and the finding that tumor cells can form vascular channels, recent studies suggest that vasculogenic processes occur in the adult. The precise identity of blood-derived angioblasts remains unclear, but it appears that cells capable of acting as angioblasts are ubiquitous in the adult. Concurrently with these studies, investigations in the embryo also have begun to suggest that the embryonic angioblastic lineage may be far more diverse than originally thought. Complicating our earlier simplistic view of neovascularization are new data on the smooth muscle cell lineage, suggesting that after birth, at least some smooth muscle cells and endothelial cells share a related if not common lineage. Participants will outline this new data and suggest new paradigms for blood vessel formation in both the embryo and adult
Apoptosis and organ injury mechanisms in hypertension
Chairs: G. W. Schmid-Schonbein and M.A. Boegehold
One of the most important unresolved issues in hypertension research concerns the mechanisms that underlie enhanced organ injury in this disease. Increasing evidence suggests that generation of reactive oxygen species may be one of the central events in the progression of experimental and human forms of hypertension. Oxygen free radical formation may serve as a pro-inflammatory stimulus in addition to its role in the elevation of arterial pressure. Aside from enhancing arteriolar tone via inactivation of nitric oxide and a direct effect on vascular smooth muscle, free radicals may also be involved in the progression of lesion formation, apoptosis and organ injury. There is also compelling evidence for immune suppression with lymphocyte apoptosis. Speakers will discuss approaches that provide insight into these mechanisms as a basis for treatment modalities that would not only target the abnormal shift in the blood pressure but also alleviate accelerated organ injury and enhanced inflammatory response to vascular challenges.
Career opportunities in physiology; taking the next step
Chair: F.L Belloni
The variety of career paths available to individuals with a Ph.D. in the physiological sciences presents both opportunity and challenge to newly trained young scientists. The "traditional" paths of academia and industry are now joined by opportunities in government laboratories, private research foundations, business, law, public policy, and venture science. Moreover, the types of positions available in even the traditional sectors have been greatly multiplied and redefined. While this situation presents unprecedented opportunity for newly trained scientists, it also presents the daunting challenge of deciding how to explore, prepare for, and achieve positions in these various sectors. This symposium will guide Ph.D. students and postdoctoral fellows who are trying to chart their own career journeys. Speakers will discuss opportunities in some of the various employment sectors noted earlier. Emphasis will be on the types of careers available, their major benefits and challenges, and how best to prepare for and seek such positions, particularly at the entry level.
Hypoxia, ischemia, Na, Ca, and cytoprotection
Chair: S. Anderson
One of the hallmarks of cell injury is lack of homeostasis in intracellular ion concentrations. Recent improvements in techniques used to measure cytosolic concentrations of sodium ([Na]i) and calcium ([Ca]i) suggest that changes in these ions are antecedent to cell injury, particularly during and after hypoxia/ischemia. Evidence is also mounting that in many cell types, flux via the Na/Ca exchanger contributes to these disturbances. This symposium will review recent advances in our understanding of the role of Na and Ca in hypoxic/ischemic cell injury in the heart, nervous system, kidney, and liver. Evidence identifying the major transport pathways involved and interventions aimed at protecting cells from injury by limiting increases in cytosolic Na and Ca will be discussed.
Sex and nonsex—estrogen and the aging hypothalamus
Chairs: J.T. Clark and J. M. Wyss
Estrogen has a well-established role in reproductive processes that involve actions in the hypothalamus. Evidence has accumulated that estrogen is also important in the regulation of non-reproductive, nonsex, functions. Thus, estrogen status regulates neuronal functioning (evidenced by neurotropic, neuroprotective, mood and cognitive effects); the central control of blood pressure and cardiovascular function (evidenced by increased incidence of hypertension, cardiovascular disease, and stroke in women after menopause); the central control of ingestive behavior (food and fluid intake), in addition to the central control of reproductive and sexual functions. This symposium will address the current state of knowledge regarding the actions of estrogens in regulating these functions in relation to aging and reproductive senescence.
Comparative models to understanding molecular mechanisms of solute transport
Chair: G.G. Goss
Despite the problems of GC rich templates and long sequences required to clone many transport proteins, there has been considerable success of late in cloning the full sequence of many different solute transport proteins from a variety of non-model organisms. The recent success is providing valuable clues to both evolutionary relationships as well as providing unique models to studying structural and physiological regulatory elements within the sequences. The great wealth of information regarding sequence structures and phylogenetic relationship will continue to grow as the full genetic codes for more organisms come online. Prediction and testing of the function of these genes in both a cellular and whole animal context will present a great challenge to the next generation of comparative biologists and biochemists. The proposed symposia will highlight various labs that have been successful in cloning transporters from a variety of organisms, and how they have incorporated a wide variety of techniques to examine and understand the function of these recently cloned sequences. Techniques for expression and analysis of transporter function from the whole animal to single cells to subcellular biochemical regulation illustrate the integrative approaches that these labs use to understand transport function.
Estrogen: a potent neuroprotective factor
Chair: P.M. Wise
Several lines of evidence establishes that estradiol is a potent neuroprotective and neurotrophic factor: it influences memory and cognition, decreases the risk and delays of the onset of neurological diseases such as Alzheimer’s disease or injury such as stroke, and attenuates the extent of cell death that results from experimental injury. Since more women will live a larger fraction of their lives in a postmenopausal, hypo estrogenic state than ever before, we must understand the circumstances under which estradiol exerts protective actions and the cellular and molecular mechanisms that underlie these novel, nonreproductive actions. Symposium participants will discuss the newest findings from studies using diverse approaches that establish the circumstances under which estradiol exerts neuroprotective actions in the adult brain. This will include data from epidemiological studies that demonstrate that estradiol influences the incidence of Alzheimer’s disease (although recent findings warn us that estrogens may not restore cognitive function when neurodegenerative pathology is in progress); studies that demonstrate the effects of steroid replacement therapy on specific aspects of cognitive function and memory; the dynamic trophic effects of estradiol on hippocampal synapses, which may be involved in learning and memory; and data that use in vitro methods to decipher the importance of neuron/glial interactions in mediating the protective effects of estradiol.
Physiology of physical inactivity’s induction of chronic disorders
Chairs: F.W. Booth and J. Holloszy
Symposium speakers will discuss the physiological basis by which physical inactivity makes an individual more susceptible to specific disorders. Any given individual inherits a particular combination of disease-susceptibility genes that contributes to the relative risk of clinical disorders. When this gene "cocktail" is combined with physical inactivity (categorized as an environmental component), a "threshold" of biological significance is crossed such that the individual is affected with overt clinical disorders. It is the job of physiologists to determine the identity of these health-disorder-inactivity genes and the mechanisms by which physical inactivity alters their expression and then to translate this basic information to prevent inactivity-induced disorders. Speakers will present the physiology that produces alterations in expressions of genes eliciting chronic disorders. Discussion will center on inactivity-induced declines in physiological function with aging, including mechanisms for the physical-inactivity-induced sarcopenia (skeletal muscle loss with aging) leading to physical frailty; the known mechanisms by which physical inactivity decreases glucose removal from blood into skeletal muscle, producing skeletal muscle insulin resistance, a forerunner of syndrome X and eventually overt type 2 diabetes; the cellular responses of arterial smooth muscle and endothelial cells to physical inactivity and how this contributes to the development of atherosclerosis; and the mechanisms by which unloading of bones during physical inactivity accelerates bone loss and the premature onset of osteoporosis
Genetic adaptation to cold
Chair: L. Wang
Speakers will examine and synthesize the phenomenology (ecological, physiological, biochemical, and cellular) and regulation (neuroendocrinological, differential gene expression, and proteomics thereof) of cold adaptation in animals living under diverse environmental challenges. Selected animal groups that combat against, conform to, or escape from cold will be representatively reviewed and compared. The anticipated outcome is to understand how physiological homeostasis can be maintained through very different thermal tactics and how these may be supported through molecular manipulations.
Epithelial channels: regulation by differentiation and growth factors
Chairs: J.D. Stockand and S. Rane
The activity and expression of numerous epithelial channels are regulated by signal transduction commonly associated with cell growth and differentiation. Recognized modulators of epithelial channels include the mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and signaling factors, such as phospholipids, associated with these cascades. Our understanding of the cellular mechanisms of action and the ramifications of modulation of epithelial channels by such signaling pathways is rudimentary. This symposium, the first directly focused on exploring regulation of epithelial channel activity by growth and differentiation factors, will address two critical issues: 1) the cellular mechanisms of action of growth and differentiation signaling cascades on epithelial channels, and 2) the physiological consequence of such signaling events. Through discussion, we hope to increase our understanding of modulation of epithelial channels by signaling cascades not traditionally associated with regulation of channel activity, and to stimulate excitement and research into this emerging area of epithelial biology.
Molecular and cellular mechanisms of ischemic liver injury
Chair: A.B. Lentsch
Ischemia of the liver and subsequent reperfusion occurs during a number of clinical relevant settings, including hepatic resectional surgery, liver transplantation, and hemorrhagic shock with fluid resuscitation. The impact of ischemia and reperfusion on the liver microenvironment includes a biphasic inflammatory injury that consists of an early, oxidant mediated component and a later, neutrophil-dependent component. Experimental models of ischemic liver injury have provided a greater understanding of the events that contribute to the pathogenesis of this syndrome and have prompted several clinical approaches to the prevention and treatment of organ dysfunction due to hepatic ischemia and reperfusion. This symposium is geared to provide comprehensive, multidisciplinary coverage of this important topic. Research presentations will include the mechanisms of oxidant production and function, sinusoidal endothelial cell responses, gender-specific responses, role of chemokines in hepatic neutrophil accumulation and liver regeneration, and cytokine regulation of ischemic liver inflammation.
Ion channels and hypoxia
Chair: D.L. Kunze
A reduction in arterial oxygen leads to a variety of physiological adjustments that may occur immediately or over minutes, hours, and days. These adjustments provide compensation that is important in maintaining physiological homeostasis. Alternatively, they may lead to unfortunate pathological states. Recently it has become increasing clear that ion channels play an important role in the adjustments to reduced oxygen in a variety of tissues. The short -term effects of hypoxia on ion channel activity may involve direct effects of reactive oxygen species on ion channel proteins or "second messengers" whose levels are modulated by oxygen. Furthermore, sustained or repetitive exposure to hypoxia may produce long-term effects on ion channels through changes in the expression levels of the channel proteins. This area is blossoming as a variety of molecular, physiological and biochemical techniques are applied to assess cellular mechanisms that underlie hypoxia-induced changes in a variety of different tissue and organs. The purpose of this symposium is to provide a forum for examining current information on the different mechanisms responsible for modulation of specific ion channels when tissues are challenged by reduced O2. The chair will introduce the topic with a short overview and will indicate the contributions of each of the speakers to the field. In this symposium we will address the responses that arise from exposure to reduced O2 in ion channels in pulmonary smooth muscle (potassium channels), carotid body (twin pore channels), and in two set of neurons (potassium and sodium channels). Most importantly, the speakers will be asked to focus on the functional consequences of these changes in channel activity or expression. They will also be asked to anticipate the future directions of research in this area.
Adaptive responses of cardiac muscle
Chair: R. Mestril
Myocardial infarction represents one of the most severe stresses to the heart. The ischemia-reperfusion injury resulting from an infarction can seriously limit the contractile performance of the cardiac muscle. Several recent studies have demonstrated that the cardiac muscle can develop adaptive responses to protect itself against the ravages of ischemia-reperfusion injury. The discovery that a short period of reversible ischemia is able to condition the heart to a subsequent damaging ischemic event, a phenomenon known as preconditioning, has created an exciting area of research. The study of cardiac preconditioning has attracted the attention of many investigators in the cardiovascular field. These studies have made us aware that the cardiac muscle possesses a diversity of means in order to adapt to stress. The search for the cellular agents that trigger preconditioning has resulted in the discovery of many potential candidates for this function, among them adenosine, nitric oxide, protein kinase C, and mitochondrial potassium ATPase channels. In addition to these potential triggers of preconditioning in the heart, a group of proteins known as the stress or heat shock proteins has also attracted much attention for their ability to protect cardiac muscle against ischemia-reperfusion injury. These proteins are responsible for thermotolerance, the ability of the cell to become resistant to thermal stress, and have been found to produce cardioprotection in transgenic mouse models. It is therefore of interest to fully explore and investigate all the potential means by which the cardiac muscle is able to adapt to stresses such as ischemia-reperfusion injury.
Redox control of skeletal muscle adaptation
Chairs: M.B. Reid and S.K. Powers
Numerous studies indicate that redox factors play important roles in many aspects of skeletal muscle biology including the regulation of gene expression, control of numerous signaling pathways, muscle atrophy, and muscle injury. Speakers will focus on redox control of skeletal muscle adaptation: redox-sensitive transcription factors and regulation of gene expression; an overview of redox issues related to skeletal muscle adaptation to heat stress and hypoxia; the role that oxidative stress plays in skeletal muscle disuse atrophy; muscle wasting associated with inflammatory diseases; and the role of free radicals in skeletal muscle injury and apoptosis.
Neural control of the cerebral circulation
Chair: W.T. Talman
It has been known since Willis’s work, well over 300 years ago, that the cerebral vasculature is richly innervated. Neural influences on cerebrovascular tone include those from local neurons, from central sites such as fastigial and trigeminal nuclei, and from peripheral sources such as sympathetic and parasympathetic ganglia. The richness and complexity of the innervation to cerebral blood vessels, the potential transmitters involved in modulating cerebral blood flow, the potential integration of neurally mediated physiological functions, and the possible relationships between disturbed physiological functions and human disease have been discussed over the past 20 years. Symposium participants will concentrate on methods for analysis of the integration between cerebral flow and spreading depression and the role played by neural mechanisms in mediating cerebrovascular responses; a review contributions from one laboratory toward a better understanding of the neuroanatomy of the cerebral microcirculation and the functional correlations of that innervation in the context of neurotransmitters released upon cerebral vessels; studies of putative neurotransmitters and other signaling molecules that modulate local cerebral blood flow in genetically altered mice; coupling of neural activity and blood flow and implications of that coupling both in health and in diseases such as Alzheimer’s disease.
Functional heterogeneity in the renal microcirculation
Chairs: L.M. Harrison-Bernard and R.D. Loutzenhiser
Optimum control of the determinants of glomerular filtration is dependent on an integrated regulation of renal afferent and efferent arteriolar tone and on the activation of mesangial cells. Blood flow to the medulla is controlled by juxtamedullary arterioles and vasa recta pericytes. Speakers will present the most recent findings addressing the regulation of renal microvascular function as assessed by direct investigations of afferent and efferent arteriolar and descending vasa recta vascular function and of the distinct intracellular signaling pathways used in each vessel segment. Investigation of the complex intraglomerular effects of angiotensin II, determined using two-photon microscopy, will be presented. Agonist-induced calcium signaling, assessed by direct measurements of afferent and efferent arteriole myocyte and vasa recta pericyte calcium signaling using electrophysiological approaches and intra-vital dyes, reveals the evolving complexity of calcium signaling events underlying the regulation of smooth muscle function along the renal microvascular network. The newest developments concerning the roles of angiotensin II receptors as regulators of preglomerular and postglomerular function will be presented and the influence of nitric oxide on basal tone and agonist-induced vasa recta pericyte contraction will be discussed. In summary, this symposium will couple hormonal actions with intracellular signaling mechanisms in preglomerular, postglomerular, and medullary microvascular segments using novel experimental techniques.
Disorders of sodium transport and blood pressure regulation
Chair: S. Linas
Although the role of salt in essential hypertension is widely recognized, the mechanisms by which the kidney contributes to sodium retention and how increases in total body sodium result in hypertension remain unclear. Several defects in mineralocorticoid production and or action as well as abnormalities in the sodium channel, ascending limb, and distal convoluted tubule sodium transport have been described. Each of these abnormalities is associated with hypertension or hypotension. The purpose of this symposium is to review molecular and cellular abnormalities in mineralocorticoid receptors and sodium transporters in the kidney and to relate these changes to clinical syndromes associated with changes in blood pressure. Finally, the symposium will attempt to put the above abnormalities in context of the hypothesis originally described by Guyton, which ascribed essential hypertension to renally mediated increases in total body sodium.
The sudden infant death syndrome, sleep, and breathing
Chair: E. Nattie
Victims of the Sudden Infant Death Syndrome (SIDS) die in sleep, possibly due to disordered breathing and autonomic control. In this session, speakers will describe brainstem abnormalities in receptor binding in the arcuate nucleus and medullary raphe of SIDS victims and outline findings in human infants on arousal, sleep, breathing and programmed learning, citing data on SIDS epidemiology. Using a chronic newborn piglet model, we will report that disruption of a homologue of the arcuate region by muscimol microdialysis decreases CO2 sensitivity, enhances the laryngeal chemoreflex, and disrupts sleep architecture including arousals. Similar disruption of the medullary raphe decreases CO2 sensitivity and alters sleep. Physiological properties of raphe neurons studied in vitro will also be described. Physiology studies in vivo and in vitro that are targeted by use of human pathological and physiological data can yield insight into the effects of specific neuron group dysfunction on protective reflexes that are possibly involved in the pathogenesis of SIDS.
Mesenchymal-epithelial interactions in lung development and repair—are modeling and remodeling one and the same process?
Chairs: J.S. Torday and C. Plopper
Lung morphogenesis and repair are characterized by complex interactions between cells of endodermal and mesodermal origins, leading to an alveolar structure. This can effectively exchange gases with the circulation. Knowledge of this complex spatio-temporal process comes from disparate disciplines—developmental biology, immunology, pathology, and genetics. By comparing common cell/molecular changes within the context of development and repair, we may gain a clearer perspective on the underlying mechanisms controlling these processes. One unifying mechanism is the establishment and maintenance of homeostasis by the "attenuated fibroblast sheath" of the lung. Participants will explore the commonalities between these complementary processes: the developmental basis for cell/molecular control of lung development; what is known about stem cells in the lung; and how they behave during lung development; and disease. Also to be discussed are the global mechanisms that mediate mesenchymal-epithelial interactions; the plasticity of mesenchymal cells in normal lung development and remodeling; and a structure-function model that may bring these concepts closer together. At the conclusion, there will be a sense of the unifying mechanisms of development and repair.
Cellular biomechanics in the lung
Chair: C.M. Waters
The lung is a mechanically dynamic organ. Cells in the lung are subjected to many different types of physical forces. For example, endothelial cells are subjected to shear stress due to fluid flow, and epithelial cells lining the airways and alveoli are exposed to tensile and compressive forces during the respiratory cycle. In the last 10 years it has become apparent that most cells throughout the body sense their mechanical environment and respond to changes. Some of these responses include changes in intracellular ion concentrations, cytoskeletal rearrangement, and changes in gene expression. Although there are significant changes in lung mechanics during mechanical ventilation and in airway diseases such as asthma, little is known about how such changes affect cellular functions in the lung. In addition, the mechanisms by which cells in the lung transduce mechanical signals into biological signals are not well understood. This symposium will explore recent findings in cellular mechanotransduction in the lungs including state-of-the-art techniques for subjecting cells to physical forces and monitoring functional changes.
Common brainstem mechanisms of cardiovascular and respiratory control
Chairs: W.W. (Bill) Blessing and J. M. Wyss
This symposium will concentrate on in-depth consideration of the common neuronal circuitry by which the cardiovascular and respiratory systems are regulated/co-regulated. Clearly, there is considerable overlap in the regulatory circuits of these systems, and to maintain homeostasis the two systems must be closely coordinated with each other. Speakers will feature innovative investigators in both arenas to consider the unified central nervous system mechanisms by which these two systems are functionally linked and their functions are coordinated. The session will highlight talks by a senior and junior investigator in each specific area, and thus accentuate how the available data and experimental tools can lead to a better understanding of the co-regulation of these functions. Each speaker will address a specific cellular or molecular aspect of the nervous system regulation and seek out the commonalities.
Role of endothelin ETB receptors in cardiorenal function
Chair: G.D. Fink
This symposium will concentrate on the physiological role of the ETB subtype of endothelin receptor, particularly as it controls renal function and systemic blood pressure. Participants will discuss work based on the development of a strain of rat with a defect in the expression of functional ETB receptors (these rats have marked abnormalities in renal function, and exhibit salt-sensitive hypertension); the regulation, localization, and function of ETB receptors in the kidney of rats with experimental hypertension; how ETB receptors modulate renal responses to changes in salt intake, perfusion pressure, and angiotensin II; and characterization of a new model of experimental hypertension produced by chronic activation of ETB receptors in the rat with the selective agonist sarafotoxin 6c. The main goal of the symposium will be to reach consensus on the role of the ETB receptor in the long-term regulation of renal function and blood pressure. Data indicate that this receptor subtype has a predominantly antihypertensive function, mediated in particular through facilitation of renal sodium and water excretion. Another goal will be to clarify the importance of vascular versus renal ETB receptors in the control of blood pressure. Finally, speakers will consider ETB receptor regulation in response to physiological stimuli such as changes in salt intake, or blood pressure. Most published work to date has focused on the ETA receptor subtype in renal and cardiovascular function; this session will synthesize current knowledge on the other major endothelin receptor subtype. Many endothelin antagonists are now in clinical trials for various cardiovascular diseases. This symposium should help establish whether blockade of ETB receptors is a desirable long-term therapeutic goal.
How to be a good mentor; how to be a good mentee
Chair: R. Davisson
Participants will discuss what is a good mentor; mentors as career advisors and role models; and special requirements of mentoring of undergraduate students, graduate students, postdoctoral fellows, and junior faculty members. For mentees, topics will include selecting graduate programs, a mentor, and a postdoc. Information on getting the most out of your training and a scientific meeting will also be discussed. Mentees will represent different stages of development (undergraduate to junior faculty). There will be opportunities to submit questions to the panel members, who will be asked to discuss how they would respond to some particular real-life issues that involve interactions of mentors and mentees. With this session, it is hoped that participation of young scientists increases at the meeting.
The promise for therapeutic intervention in obesity: the brain and beyond
Chair: D. D’Alessio
This symposium will focus on recent advances in understanding the physiology of energy balance and control of food intake. This progress in experimental neuroendocrinology now holds hope for novel treatment strategies for obesity and disturbances of food intake.
Potentiation of the development of atherosclerosis by diabetes
Chair: B. Draznin
Speakers will address the structural changes in the vasculature in response to diabetes, and the molecular changes contributing to these effects.
Endothelial dysfunction in end-stage renal disease
Chairs: M. Goligorsky and C. Baylis
The topic in this symposium is the contribution of endothelial dysfunction to the pathogenesis of end-stage renal disease. This will be approached through discussion of specific molecules implicated in this process, including homocysteine, NOS, and endogenous inhibitors of NOS such as ADMA and 1-NMMA.
Diagnosis and treatment with atrial natriuretic metabolism
Chair: D.L. Vesely
This symposium will concentrate on translational research of basic science findings of new cardiac hormones for the diagnosis and treatment of clinical disease, characterized by salt and water rentention such as congestive heart failure and acute renal failure. These hormones, synthesized mainly in the heart, consist of a family of peptide hormones that are referred to as atrial natriuretic peptides since they are synthesized mainly in the atrium of the heart and have natriuretic (i.e., salt excreted in) properties.
Rhythms in reproduction
Chairs: R. Guevara-Guzmán and R. Hudson
Various forms of rhythmicity are being found to underlie the behavioral and physiological organization of biological systems. Reproductive processes are no exception. Participants will discuss the contribution being made by biological rhythms research to understanding reproductive processes by presenting examples of recent work in rabbits and rats across the reproductive cycle: from courtship and mating, through pregnancy and parturition, to the interaction between mother and young. Speakers will outline the particular contribution of behavioral and physiological rhythms to these processes and consider possible neural and endocrine mechanisms underlying them.
Bioengineering approaches to enhance gene delivery
Chair: M. Davis
Nonviral, nucleic acid delivery systems have exhibited problems such as low gene transfer efficiencies, high toxicity, and low in vivo stability. Strategies for overcoming some of the barriers to effective gene transfer have emerged. This session will concentrate on issues of importance to the engineering of the next generation nonviral delivery methods for nucleic acids. Topics will include new materials for nucleic acid delivery, new insights into extracellular and intracellular delivery mechanisms and the rational design of fully formulated vectors.
Nanotechnology in bioengineering and biology
Chair: T. Des
Nanotechnology is changing the way we view the biological world. With recent developments in the synthesis, characterization, and application of nanostructures, we have significantly advanced our understanding of biology and medicine. Nanoscale features can mimic the biological world, giving us unprecedented control and manipulation over our environment. From biomimetic materials and biomolecular surface modification to single molecule imaging and drug delivery systems, nanotechnology will pave the way towards a new biotechnological frontier. This session will examine some of the many aspects of nanotechnology related to biology and medicine.
Manipulations to enhance new tissue formation
Chair: F.C-P. Yin
Engineered tissues can be achieved by many different methods. The most commonly used one to date involves using a scaffold on which one grows cells of interest. The scaffolds consist of man-made or natural materials that may or may not resorb. The major drawback to this approach is the lack of control over the resulting mechanical properties of the tissue. As our understanding of cell biology increases, it has become clear that certain physical and chemical manipulations affect cellular morphology, signal transduction pathways, gene expression and the type and properties of extracellular matrix produced by these cells. This symposium explores some of these issues by focusing on the effects of various manipulations on the properties of the resulting tissues.
President’s symposium: signaling in cells of the microvascular wall
Chair: I. Sarelius
This session will highlight mechanisms of communication between cells of the microvascular wall and/or between the microvascular wall and the surrounding environment. The goal is to highlight recent advances in our understanding of signal transduction in smooth muscle or endothelial cells in the context of how they are reflected in functional responses of intact vessels.
The role of angiotensin and oxidative stress in the development of hypertension
Chair: J.C. Romero
The mechanisms responsible for maintenance of hypertension in the presence of "normal" plasma renin activity have remained elusive. Even with normal or decreased levels of angiotensin, however, blood pressure is normalized after administration of either converting enzyme inhibitors or angiotensin antagonists. Similar responses are observed in rat models of hypertension (i.e., spontaneously hypertensive rats, Dahl salt-sensitive rats, etc.). Most, if not all, of the characteristics of essential hypertension can be generated by infusing subpressor doses of angiotensin II (from 5 to 15 ng/kg/min); these produce a significant increase of blood pressure on the third day of administration. This "slow response" to angiotensin II, which has been demonstrated in rabbits, dogs, rats, swine, and man, is indicative of a temporal requirement for activation of additional vasoconstrictor(s) process(es). One such process may be oxidative stress. In fact, angiotensin II stimulates production of superoxide via membrane NADH/NADPH oxidase activation. The chemical reaction of superoxide with nitric oxide yields peroxynitrite (OONO), a potent oxidant that could oxidize arachidonic acid and release antinatriuretic vasoconstrictors such as 8-isoprostaglandin F2
(isopros-tane). Angiotensin II may also stimulate endothelin synthesis (ET), which can be increased further by oxidative stress. The interrelationship between angiotensin II, oxidative stress, and ET could lie at the root of the pathophysiology of essential hypertension and may also explain gender differences in blood pressure since testosterone appears to stimulate angiotensin and oxidative stress. That these effects of angiotensin are specifically activated when tissue or plasma levels become inappropriately high with respect to existing fluid volumes, the clinical data demonstrating that many individuals with essential hypertension exhibit an inability to regulate angiotensin levels in response to volume expansion, and the animal and human studies showing that blockade or inhibition of oxidative stress and/or angiotensin results in normalization of blood pressure provide further evidence for the importance of oxidative stress in the development hypertension. This symposium will discuss these and other data related to this hypothesis.
Cyclooxygenase-2 and renal function
Chairs: F.J. Salazar and J. Schnermann
The role of cyclooxygenase-derived metabolites in regulating renal function has been demonstrated in numerous studies performed by many groups. Contrary to other tissues and organs, in which only one cyclooxygenase (COX) isoform is constitutively expressed (COX-1), there is a constitutive expression of both COX isoforms (COX-1 and COX-2) in the kidney. Speakers will summarize the data that demonstrate that COX-2 is constitutively expressed in the renal cortex and renal papilla and that COX-2 derived metabolites play an important role in the regulation of renin release, renal hemodynamic, and sodium and water reabsorption. Results showing that there is an important interaction between COX-2 derived metabolites and other regulatory mechanisms (nitric oxide, angiotensin II and norepinephrine) in controlling renal function will also be presented.
Everything you ever wanted to know about the IACUC but were afraid to ask
Chair: J. Stallone
This half-day program will describe the workings of the Institutional Animal Care and Use Committee (IACUC).
This program is specially adapted from the "IACUC 101" series developed by the Applied Research Ethics National Association (ARENA) and the American Association for Laboratory Animal Sciences. It is intended to address the concerns of research scientists. It will provide information useful both to scientists who serve on IACUCs and those whose protocols require IACUC review. It is an opportunity to ask IACUC experts and representatives of regulatory authorities what the IACUC is actually required to do and how principal investigators are supposed to cope with these demands. The quality of the oversight of research involving humans and animals is subject to scrutiny as never before. IACUCs have an enormous responsibility to ensure the humane care and use of laboratory animals. Topics will include: IACUC functions and responsibilities; the laws, regulations, and policies that govern animal care and use; why the IACUC inspect labs; why staff must take training; why the protocol form is so detailed; why the review process takes so long; why the IACUC is so picky; why these procedures keep getting more complicated and time-consuming; and what they will come up with next, and what can be done about it. Each presentation will be followed by a question-and-answer session with representatives of the major governmental and non-governmental oversight agencies: NIH’s Office of Laboratory Animal Welfare, USDA Animal Care program, and the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC).
Other symposia
Physiology InFocus—translating the genome: physiology and pathophysiology of obesity
Organizer: J.E. Hall
Gene-environment interactions in obesity
Chairs: T. Kurtz and J. Hill
Neurobiology of obesity
Chairs: W. Haynes and M. Schwartz
Endocrine/metabolic consequences of obesity
Chairs: B. Horwitz and B. Kahn
Obesity and cardiovascular regulation
Chairs: A. Mark and J. Hall
New developments in renal acid-base transport and its regulation
Chairs: M.A. Knepper and S. Wall
Role of myostatin in regulating muscle growth
Chair: S-J. Lee
Minisymposia
Viruses, ion channels, and ion transporters
Chair: J.M. Russell
Viruses, genetic material surrounded by a protein coat, must enter host cells where they usurp host cell machinery in order to replicate. Different viruses use different mechanisms to cause the host cell to become an efficient viral incubator. In recent years, it has become increasingly evident that host cell mechanisms of transmembrane ion transport are among the key targets in the viral strategy of replication. The reasons for such targeting remain unknown. Studies of viral effects on host cell transmembrane ion transporters are likely to yield not only the expected information about specific viral effects, but also, and perhaps more interesting, important new insights into mechanisms and functions of normal ion transport mechanisms. This minisymposium will highlight some of these effects of viruses and bring us up to date on what such studies can teach us.
The sensory functions of the DEG/ENAC superfamily of ion channels
Chairs: D. J. Benos, B. A. Stanton
The more than 30 members of the ever-growing superfamily of ion channels known as DEGenerin—Epithelial Na+ Channel (DEG/ENaC) have been found in organisms ranging from nematodes to humans, and are expressed in cells and tissues as diverse as kidney, lymphocytes, and tongue. These channels have been implicated in numerous physiological functions, such as taste, hearing, and smell, mechanosensation, pain perception and Na+ homeostasis. Moreover, these channels have been implicated in several important human diseases (e.g., hypertension, cystic fibrosis, ARDS, brain tumors, and the flu). This 2-hour minisymposium is designed to provide an authoritative update on current research into the physiological sensory functions of this important class of ion channels. Participants will review the general properties of DEG/ENaC regulation, focusing on regulatory inputs from protein associated with the channels and having a potentially important role in sensory transduction function; ENaC’s role in taste, olfaction, and voice tonation; and the role of the neuronal branch of the DEG/ENaC superfamily, the BNaCs or acid-sensing ion channels, in transduction of mechanical stimuli.
Refresher course
Recent advances in neuroscience
Chairs: C.M. Heesch and T.J. Cunningham
The teaching of neurophysiology represents a significant challenge for physiologists. The field of neuroscience is rapidly developing, and the rapid pace of research causes textbook material to become outdated, often within a few years of publication. The curricular location of neurophysiology material varies greatly between medical schools. Neurophysiology may be included in a traditional physiology course, it may be combined with anatomy in neuroscience course, or there may be no definable venue devoted to teaching neurophysiology. This refresher course will provide updates on four topics in neurophysiology: the autonomic nervous system, our evolving understanding of cognition, movement, and the hypothalamus.
Workshops
Physiology and risk assessment: predicting adverse effects of new chemicals on critical organ functions
Chairs: L.B. Kinter and A.S. Bass
Physiological functions are gaining international recognition as important biomarkers’ for potential life-threatening effects of new chemicals. Termed ‘Safety Pharmacology’ (perhaps more accurately ‘Safety Physiology’), this latest nonclinical discipline was recently accepted by the International Conference on Harmonization (ICH) as an integral part of worldwide guidelines for pharmaceutical development. The new guidelines define organ systems and functions to be evaluated, and points to consider for study design and conduct (CPMP/ICH/539/00). Unanticipated chemical effects on physiological functions can result in medical emergencies. The new ICH guidelines recognize that while in vitro studies of molecular targets (enzymes, receptors, ion channels, etc.) suggest mechanisms by which chemicals might affect critical functions, organ functions are complex, integrative, and most usefully evaluated in their totality in intact (and ideally unanesthetized) animal models. Assessments of physiological functions in animals can elucidate the significance of chemical interactions with molecular targets and provide biomarkers for subsequent clinical studies. Physiological function data also enhances general toxicological endpoints used for risk identification/risk assessment. Workshop speakers are those whose works and concepts have been influential in obtaining ICH acceptance of physiological functions as biomarkers for detecting adverse effects of new drugs, to present and interpret the new guidelines and to provide insight and practical experience for design, conduct, and interpretation of organ function evaluations for risk assessment. Presentations will focus on the emergence of applied physiological organ function assessments as a modern discipline in pharmaceutical development, and will discuss the core organ system/function evaluations. The session should interest academic and industrial physiologists participating in pharmaceutical development, and will specifically underscore the growing need for training in applied organ systems physiology.
Bioinformatics in physiological genomics
Chair: P. Tonellato
This training workshop is targeted to early and potential users of bioinformatics who have a strong background in biomedical wet-lab science, but less familiarity with biomedical databases and analysis tools. The focus of the training will be to expose the audience to concepts behind the collection, organization and access to biomedical datasets and databases in general, discussion of strategies and experimental designs that use emerging technology to collect data to conduct biomedical science; and to present the concepts and tools used in the analysis of datasets with discussion of potential spin-off analysis when publicly available data are coupled with local experiments or studies. Basic concepts of genomics, phenotype and microarray expression, analysis and interpretation will be reviewed. Handout material will provide a set of exercises to introduce the trainee to practical analysis useful in gene hunting, sequence analysis, map (genetic, RH, physical and comparative) construction and interpretation, expression profiling and interpretation and general genomic and genetic data and information gathering.
Incorporating case studies in the physiology classroom
Chair: W.H. Cliff
Although case study analysis is used effectively for students studying business, law, medicine, education, psychology, and the like, case study teaching has not yet found widespread use in physiology. Even instructors who might be inclined to use case study analysis may be hesitant to adopt it if they are uncertain how best to implement it in the classroom. This workshop will explore strategies for incorporating case studies into the range of physiology courses found in different academic settings (community college, four-year undergraduate, graduate/professional). After receiving a short primer on case studies and the ways that they can be used, workshop participants will be provided with a representative sample of cases in physiology and arranged in small working groups. Guided by a planning template that identifies a series of issues and concerns central to the effective use of case studies, each group will be encouraged to create a favorable strategy for managing case study teaching in the classroom. Then, each group will report on their plan. During this review of individual strategies, four experienced case study teachers will serve as discussants, providing informed commentary that will facilitate group discussion and draw out general observations and conclusions about successful classroom management of cases in physiology.
Understanding organ function through real-time fluorescence microscopy
Chairs: J. Bhattacharya and B. Pitt
The application of real-time fluorescence microscopy (RTFM) in conjunction with rapid image acquisition and image analysis has provided novel insights into cell function. RTFM is widely used with both wide angle and confocal microscopes for the quantification of second messengers such as intracellular free Ca2+ concentration ([Ca2+]i) and reactive oxygen species, in order to determine enzyme activities and detect protein and gene expression. Although the bulk of this research has been done in cultured cells, recent reports indicate that the application of RTFM to the whole organ is likely to advance the understanding of cell function in situ. This workshop will bring together experts who have developed organ RFTM. They will outline the principles, advantages, and limitations of the approach for whole organ studies: optical principles underlying light microscopy; equipment strategies; the lung model for RTFM; and the two-photon concept in relation to glomerular imaging. The workshop should appeal to those seeking a novel approach to investigating organ function.
American Society for Biochemistry and Molecular Biology
Symposia
THEME 1: Cellular Control
Role of mitochondria in apoptosis
Chair: D. Green
Control of cholesterol homeostasis (in memory of Konrad Bloch)
Chairs: D.E. Vance and H. Goldfine
Konrad Bloch was one of the small group of biochemists who first used stable isotopes to study the biological synthesis of complex molecules. His pioneering work on the formation of cholesterol in cells played a large role in the eventual unraveling of a pathway involving more than 25 enzymes. His work on fatty acid synthesis revealed the different mechanisms used by bacteria and eukaryotic cells to introduce a double bond into unsaturated fatty acids. This and other work led to an understanding of the use of oxygen as a biosynthetic reagent by eukaryotic cells either to replace existing anaerobic pathways or to synthesize molecules unknown in the prokaryotic world. Extension of his work on fatty acid synthesis led to the discovery of an acetylenic "suicide substrate" one of the first of this class of enzyme inhibitors. Bloch’s work was recognized by the award of a Nobel Prize in Physiology or Medicine, which he shared with Feodor Lynen in 1964. The chairs will present an introduction to the life and work of this remarkable scientist. The major impact of Dr. Bloch’s work was in the 1940s to 1970s. In the last 30 years, Michael Brown and Joseph Goldstein have been the world leaders in cholesterol research that has also affected numerous other fields in cell biology, biochemistry, and medicine. They discovered the low-density lipoprotein (LDL) receptor and demonstrated that it functioned to regulate the levels of LDL in plasma. The work was also pioneering in understanding the general mechanisms by which cells bind and internalize proteins. For this work, Brown and Goldstein shared the Nobel Prize in Physiology or Medicine in 1985. They have continued their innovative and pioneering research and discovered sterol regulatory element binding proteins (SREBPs) that have a central regulatory role in cholesterol and fatty acid metabolism. The lectures will focus on the processing of the SREBPs in isolated cells, stressing the roles of SREBP cleavage-activating protein (SCAP) and two proteases; the roles of SREBPs in controlling synthesis of unsaturated fatty acids in liver and the implications for obesity, insulin resistance and diabetes; and the somewhat different role of SREBPs in Drosophila.
Endoplasmic reticulum stress response
Chair: R.J. Kaufman
Cell cycle M-phase control
Chair: J.W. Harper
THEME II: Gene Regulation
Signaling to the nucleus and beyond
Chair: B.J. Graves
Regulation of gene expression is mediated by both extracellular and intracellular signals. In many regulatory pathways, signals flow through kinase cascades to specific transcrip-tion factors. The resultant posttranslational modifications act at a variety of levels to change the activity of transcription factors, including nuclear localization, oligomerization, DNA binding as well as co-activator or co-repressor binding. This symposium will bring signal transduction pathways not only to the nucleus but also into the nucleus to demonstrate the consequences of signal transduction at the level of transcription factor biochemistry. Topics will span from development to cell activation and cancer.
Chromatin remodeling machines
Chair: S.Y.R. Dent
The regulation of gene expression in eukaryotes is directly affected by the packaging of the genome into chromatin. DNA is spooled around octamers of histone proteins to form nucleosomes, which are then folded into higher order chromatin structures. Both the placement of individual nucleosomes and the degree of chromatin folding can directly affect transcription by limiting access of basal and regulatory factors to their target sequences. Chromatin remodeling is usually achieved either through posttranslational modification of the histones or through mobilization of nucleosomes via the action of ATP-dependent factors. Speakers will discuss the enzymes and molecular mechanisms that govern chromatin remodeling. Of special interest are the ways in which complex, multisubunit chromatin remodeling machines are directed to particular genes and the ways in which the various components of these factors interact.
Shuttling to and from the nucleus
Chair: D.J. Forbes
Messages pass constantly from the extracellular world into the interior of the cell. Often these messages must travel to the nucleus in order to affect cellular change. A necessary step in passage through the elaborate, highly regulated nuclear gateway, the nuclear pore. When traffic is perturbed, cancer, developmental defects, or aberrant cellular function can ensue. The vertebrate nuclear pore, many times larger than the ribosome, is 120 million daltons in size with a complex structural architecture and 30–50 different proteins (<20 are known). In yeast the full complement of its 32 nucleoporins were recently reported. Much progress has also been made in discovering the soluble import and export receptors that ferry cargo through the nuclear pore. For both yeast and vertebrate systems abound, What is the full cast of proteins required to form the nuclear pore? What is the mechanism of action of this very large cellular machine? Motors do not appear to be involved and interesting alternate models have been proposed and will be discussed. It is also becoming clear that traffic through the nuclear pore is tightly controlled. Small transport factors, such as the small GTPase Ran and the accessory protein NTF2 play a large role in this control. The session will highlight progress on these fronts.
Protein trafficking at membranes
Chair: R.E. Jensen
The faithful targeting of proteins from their site of synthesis, usually in the cytosol, to a specific destination, such as a cellular organelle, is a fundamental problem in eukaryotic cell biology. Moreover, at the target membrane, some proteins are translocated completely across the membrane into the interior of the organelle, whereas other proteins are inserted into the organelle’s bilayer. While much of the machinery mediating the translocation of proteins to and into specific organelles has been identified, the mechanisms by which this machinery fuctions is understood only at a basic level. Session speakers will discuss new finding on the mechanisms of protein import into mitochondria, chloroplasts, peroxisomes, and the endoplasmic reticulum.
Theme III: Proteomics
Protein machines
Chair: J.S. Choudhary
Most proteins are though to exist in the cell not as free entities but as part of cellular machines, which regulate and integrate cellular functions cooperatively. The ability to identify protein interactions and complexes is important for assigning protein function, the principal focus of numerous projects in the postgenomic stage. Participants will discuss the application of diverse experimental and informatics methods that are effective for characterizing protein function. Speakers will describe both small- and large-scale studies for isolating and characterizing specific protein interactions and functional complexes, report on the use of protein chips for identifying protein activities, and present the first study on the functional organization of a eukaryotic proteome based on the systematic large-scale analysis of protein complexes.
Chemically reactive probes for proteomics and drug discovery
Chair: J.A. Wells
Protein dynamics and function
Chair: A.G. Palmer, III
Advances in experimental and computational methods for characterizing dynamical properties of proteins are providing new insights into the coupling between motional processes and function in folding, ligand recognition, and catalysis. Speakers in this session will highlight recent developments and applications of NMR spectroscopy, molecular dynamics simulations, and optical spectroscopy for identifying and quantifying dynamic processes in proteins. The implications of the quantitative results for protein function will be emphasized. Questions to be addressed include the role of conformational entropy in ligand recognition and protein folding as well as the contribution of loop and domain motions to product release in enyzmes and to activation of receptors.
Evolution of function in (b/a)8-barrels
Chair: J.A. Gerlt
The (b/a)8-barrel fold is the most commonly observed fold for enzymes. The common occurrence of this fold may be the consequence that it is particularly well-suited for the evolution of new enzymatic activities from progenitors: the catalytic groups are located on the loops that connect the C-terminal ends of the b-strands with the following a-helices. Speakers will discuss examples of three possible evolutionary strategies for the evolution of new function: 1) the progenitor provides structural features that facilitate a shared partial reaction; 2) the progenitor provides the template for binding a common ligand; and 3) the progenitor provides functional groups that can be used in different mechanistic and metabolic contexts. An understanding of the strategies that nature uses to evolve new functions may both facilitate assignment of function to proteins of unknown function in sequenced genomes and also assist in the rational design of new catalysts.
Minority Affairs Symposium
Underrepresentation of minorities in science: can the leaks in the pipeline be fixed?
Chairs: P.A. Ortiz and T.D. Landefeld
Many students who begin the study of science fail to complete their academic studies, particularly students of color and those from otherwise disadvantaged backgrounds. This increased degree of attrition occurs at all academic levels, from elementary education to postgraduate study. The reasons for this can be attributed to the lack of scientists from diverse background (thereby creating a dearth of role models) and the inadequate attention to issues that disproportionately affect those groups. The attrition of young scientists has also been traced to inferior education and increased pressures to leave academic study. Although both of these causes can be attributed to many factors, socioeconomic pressures play a large role in determining the quality of a student’s science education, the educational opportunities from which a student can select, peer expectations, and familial obligations. Speakers will identify factors that contribute to the leaky pipeline, mechanisms that exist to "patch" the pipeline, and techniques to improve the retention of minorities in the sciences.
Focus Groups
Regulation of development and immunity by glycoconjugates
Chair: J.B. Lowe
Lipid traffic and enzymology in membrane assembly
Chair: D.R. Voelker
Lipid synthesis and transport are two of the most fundamental elements of membrane biogenesis. The mechanisms by which lipids are transported among different membranes within cells remain largely unelucidated. The topology of enzymes involved in some of the metabolic processes is also critical to understanding elements of the interorganelle tranfer process. Increasing evidence indicates that glycerophospholipids can move between membranes by mechanisms that are independent of the well-known vesicle budding and fusion processes that regulate membrane protein traffic. Presenters will discuss recent work identifying mutant bacteria, yeast and mammalian cells with defects in lipid transport and metabolism; the genes that complement these defects and their possible mechanisms of action; and the role of specific enzymes in compartmentalizing lipid pools for either futher metabolism or function.
Animal models for the study of metabolic processes
Chair: R.W. Hanson
Understanding the regulation of metabolism in mammals requires a coordinated approach that integrates the function of the diverse organs involved in the control of metabolic pathways. This requires studies using animals to fully understand the complexities of metabolic control. The advent of molecular genetics, and with it the ability to manipulate the genome of mice, has provided an exciting tool for a systematic analysis of the role that specific regualtory proteins and key enzymes play in the control of metabolism. These animal models also afford insight into the genetic basis of metabolic diseases. This session will present a selected cross-section of the exciting possibilities for the study of metabolic regulation provided by genetic manipulation of animals. Speakers will focus on animal models that emphasize the control of carbohydrate and lipid metabolism and will include an analysis of the role of the transcription factors in the forkhead sub-family of genes on insulin action. The role that the luconeogenesis enzyme phosphoenolpyruvate carboxykinase plays in Type 2 diabetes, using mice in which the gene for this enzyme has been over-expressed in the liver, and a mouse model for glycogen storage disease Type 1b, which should help in developing novel therapies for the treatment of this metabolic disorder, will also be discussed. In addition, presenters will detail the metabolic relationship between homocysteinemia and atherosclerosis based on studies using mice in which the genes for cystathionine 
-synthase and apolipoprotein E have been deleted. The long-term metabolic consequences of dietary patterning in the perinatal period on alterations in lipid and carbohydrate metabolism in the rat have been explored in detail using the "pup-in-the-cup" model. This research has established a clear link between the excessive consumption of carbohydrate during the suckling period and subsequent development of obesity in the adult.
Biological catalysts and their regulation
Chair: V. Schramm
Life depends on the ability of protein and RNA catalysts to accelerate and control the rate of chemical reactions. Questions explored in this group will center on the chemical and structural strategies that have evolved to provide function to the biological catalysts. In addition to achieving fantastic catalytic rate accelerations, this power must be closely controlled to satisfy the needs of the host organism. Ribonucleotide reductases produce and control the deoxynucleotides required for DNA synthesis and repair, using metals and radical-centered reaction chemistry. Structures of the three classes of ribonucleotide reductases are now available for chemical and regulatory insights. Catalysis by RNA also features metal ions, but RNA lacks organic cofactors and the variety of the acids and bases found in protein catalysts. Examination of RNA enzymes reveals some fundamental principles of catalysis. Principles common to all biological catalysts are the need to sequester reactive intermediates from other cell components and the need to evolve catalysts in order to remove otherwise lethal agents from the environment and provide a structural context for catalysis linked to conformational events. Structural genomics approaches to enzyme classes reveal unexpected variation in many enzymes, establishing convergent evolution to common functions.
Educational and Professional Development Symposia and Activities
Teaching biochemistry I & II—new methods and new content
Chairs: J.E. Bell and C.E. Rohlman
Two coordinated symposia will focus on a variety of educational issues in biochemistry and molecular biology. As we step into the 21st century, education in biochemistry and molecular biology is faced with a dilemma: what is biochemistry and molecular biology in today’s world of bio-informatics and proteomics and how do we prepare students for the challenges of an increasingly complex and diverse future in the molecular life sciences. What background must students have? What skills must they acquire? And how do we ensure that all students, whether future biochemists and molecular biologists or not, appreciate and understand the quantitative aspects of the discipline? Presenters will thread these themes through both symposia. The first session will concentrate on ways to enhance student understanding of the quantitative and interdisciplinary nature of biochemistry and molecular biology and will feature innovative ways that are being used to foster both the research paradigm of learning and the integration of the fundamentals of the life sciences: the necessary background of chemistry, physics, biology and mathematics into courses that focus on "need to know" learning. The second symposium will address ways to integrate recent advances in computational chemistry, bio-informatic and proteomics into the undergraduate curriculum, and what needs to be taught to prepare students for the future in these areas.
Careers in the biotechnology and pharmaceutical industries
Chair: A.S. Dahms
Speakers will discuss current hiring trends in the biotech and pharmaceutical industries, recommend how to get in the "front door," present new ideas on marketing oneself, and afford a networking environment. Representatives from industry, academia, and professional recruiting firms will compose the panel.
Digital libraries and publishing in the electronic age
Chair: M. O’Leary
The last decade has seen incredible changes in the management of scientific information thanks to the World Wide Web. This evolution of new information management systems continues, and the outlines of the next generation of information tools are barely in sight. This session will be concerned with digital libraries, on-line journals, use of media in teaching, and other issues of information technology.
New perspectives on women in science
Chairs: E. Sabban and J. Voet
Overt discrimination has almost disappeared, yet women are still underrepresented at the higher levels of science, compared to their proportion of Ph.D. recipients. Speakers will discuss possible reasons for this "leaky pipeline" in the advancement of women and why so few achieve full professorship. Topics include the findings of recent surveys on gender in higher education faculties that were the basis of a recent Capital Hill briefing; results of a new report from the National Academy of Sciences on gender differences in the careers of doctoral scientists and engineers; factors resulting in differences between progression of careers of men and women, including familial obligations; personal perspectives of the major advances in the representation of women and the challenges that remain for achieving full gender parity in the higher echelons of science; and suggestions and insights into dealing with the unique challenges of achieving scientific excellence while maintaining a family and one’s sanity, simultaneously.
Women scientists’ mentoring session/reception
Chair: A.J. Wolfson
Although the number of women studying biochemistry at the undergraduate level now equals or exceeds that of men, women are still underrepresented in the professional ranks and higher levels of administration. This program, now in its third year, offers a forum for discussing personal histories and strategies for increasing access for women in biochemistry, and presents alternative career paths. In conjunction with other, more formal sessions, this panel and reception will feature women biochemists sharing their own professional experiences and will allow formation of mentoring partnerships.
Special Sessions
What’s real in all these microarray data: learning to trust your intuition while using sound statistical methods
Chair: R.L. Niece
How can researchers most expeditiously assimilate information from thousands of data points gathered in the course of experiments using microarrays? How can the data be screened or reduced to eliminate irrelevant data points? What can be done to make the data a manageable set that can be treated statistically? How can scientists develop experimental designs to make their experiment efficient and the interpretation of the results robust? Speakers will address approaches to designing microarray experiments, distinguishing significant data from false positives, and defining genes whose expression patterns mark noteworthy physiological conditions in the course of disease. After collecting expression data for thousands of genes from many tissues in studies of susceptibility and development of diseases, speakers have identified multiple genes on different chromosomes. The information developed from array experiments will subsequently be discussed for the specific diseases, relating the microarray experiments to the biology and medicine of the disease models.
NIH and NSF funding opportunities—grant-writing tips
Chair: T.S. Woodin
This session that will explore the various types of funding opportunities available to: beginning and midcareer faculty, facutly at various types of institutions (2-year, 4-year liberal arts, masters, and research institutions) interested in research or education or in combining the two, and graduate students. In addition to an overview of appropriate programs, there will be suggestions for effective grant writing and the opportunity to ask questions.
Research funding by the American Cancer Society
Chair: C.C. Widnell
The American Cancer Society (ACS) has recently introduced major changes in its Extramural Grant Progam: Research Scholar Grants, now awarded up to a maximum of $1 million over 4 years, have replaced the previous Research Project Grants. Postdoctoral Fellowships have been increased to a maximum of $118,000 over 3 years. ACS program directors, members of the peer review commit-tees, and a recent awardee will discuss the details of the programs, the submission and review of applications, and the characteristics that result in an application receiving an "outstanding" rating.
Closing symposium
Proteomics and drug discovery
Chair: R.A. Ikeda
The National Institute of General Medical Sciences (NIGMS) is marking its 40th anniversary in 2002. During the past four decades, the institute has supported basic biomedical research with the goal of advancing the understanding of fundamental life processes. Recent NIGMS initiatives have emphasized collaborative and interdisciplinary approaches to science. This closing session will highlight progress in the areas of these initiatives. Speakers will describe recent advances in the use of proteomics to characterize G-protein-related phenomena in the B lymphocyte and the cardiac myocyte, the effect of advances in computational proteomics on rational experimental design, and advances in the use of structural genomic approaches to facilitate biological discovery.
Satellites
Satellite I—Transcriptional regulatory mechanisms
Chairs: J.W. Conaway, R.C. Conaway, and A. Shilatifard
This satellite meeting will cover a broad area of transcriptional regulatory mechanisms in both eukaryotic and prokaryotic organisms. The two keynote speakers will combine ideas from eukaryotic and prokaryotic model systems, using studies on mechanisms of transcriptional regulation in eukaryotic and prokaryotic organisms. Other sessions will encompass basic transcription, activation, and repression mechanisms and chromatin and transcriptional regulation. This forum will allow younger scientists, including postdoctoral fellows and graduate students, to showcase their work through platform lectures and posters and to interact with more senior colleagues. In addition, there will be a lecture, Transcription coupled to DNA repair. Where we are.
Satellite II—Scientific and technical challenges of the human proteome
Chairs: A.L. Burlingame and J.T. Stults
Having a growing number of entire genome sequences in hand, scientists’ attention has shifted to studies of genome expression, focusing on the interplay between cellular messager RNA levels and protein expression, composition and function. Presenters will provide an overview of the demanding technological and strategic issues that are under current development in proteomics. These issues include the relative merits of electrophoretic separations vs multidimensional chromatographic methodologies for separation of complex protein mixtures such as cell lysates and immunoprecipitates, and the mass spectrometric strategies for protein identification in these experiments. Further challenges involve 1) how to sample the dynamic range of protein expression adequately while achieving global quantitative measurement of protein expression, 2) the methods required for studies of membrane proteins, and 3) the more demanding and tedious tasks involved with structural characterization of most posttranslational modifications, such as phosphorylation and glycosylation, and determination of their site-specific stoichiometry.
Satellite III—Combinatorial signaling
Chairs: S.J. Parsons and R.A. Bradshaw
The past 20 years have witnessed an explosion of information regarding the intracellular signaling pathways that cells use to respond to environmental cues or factors. Sometimes these factors direct the cell to do conflicting things, such "to grow vs to differentiate or undergo programmed cell death." Signaling pathways emanating from single receptor classes, like tyrosine kinase receptors, G-protein-coupled receptors, and cytokine receptors, have been elucidated. But today’s challenge is to learn how a cell integrates all the different extracellular signals it receives to respond in a specific and singular way. To initiate studies to answer these questions, investigators have begun examining how different signaling pathways that emanate from two distinct receptor classes network within the cell to elicit a cooperative or antagonistic response. This Combinatorial Signaling session will address several examples of such "mixed signals": 1) integration of extracellular matrix-induced signals (adhesion and migration) with growth factor-induced signals, and 2) cross-talk between G-protein coupled receptor-, steroid receptor-, or cytokine receptor-induced signals and tyrosine kinase receptor-induced pathways. Discussions begin with receptor oligomerization and activation and continue through signaling networks and gene expression. These studies begin to consider the strength of signal and complexity of signals vs response. They are noval and groundbreaking and are likely to represent the forefront of many such investigations yet to come.
Workshop
How to get students actively involved in learning, even if you have 300 of them in the class
Chair: H.B. White, III
If educational researchers agree about nothing else, they agree that people learn best by doing things and reflecting on what they have done, not by watching and listening to someone else telling them what to do. While a good lecture has the power to instruct and even motivate students, if lecturing is the only thing that happens in a 50-minute (or 75-minute or 3-hour) period, the chances are that much less learning is happening than would happen if other more active methods were mixed in. What can instructors do to get students active in class without losing control of the class or of the syllabus, especially if the class is large? This presentation offers and illustrates several proven techniques for achieving this goal.
American Society for Pharmacology and Experimental Therapeutics
Symposia, Special Sessions, and Workshops
The neurobiology and neuropharmacology of Alzheimer’s disease: treatment strategies
Chairs: S. DeKosky and D.B. Schenk
Sessions will include clinical, neurochemical, and neuropathological alterations in Alzheimer’s disease (AD); amyloid and amyloid therapeutics; Tau and AD; neuroimaging and AD; and neurotransmitter therapy interventions.
Regulation and function of human extrahepatic cytochrome P450
Chair: X. Ding
Extrahepatic tissue P450 enzymes play important roles in the metabolic activation and toxicity of environmental as well as therapeutic agents. However, we still know very little about the expression, regulation, and metabolic capacity of P450 enzymes in human extrahepatic tissues. Several investigators will focus on these enzymes in selective organ systems in both humans and animals.
Novel antithrombotics: assessing activity, safety, and efficacy
Chair: R.J. Leadley
Thrombosis is an important research area for pharmacologists, from drug discovery to pharmacokinetics to clinical development. Many lessons are being learned in this area as we gather more data from clinical trials with drugs specifically targeted toward unique mechanisms. Speakers will share some of those lessons and update the "hottest" compounds and approaches in antithrombotic pharmacology.
I. CRH receptors, agonists, and antagonists: basic pharmacology
II. CRH receptors, agonists, and antagonists: drug discovery and development
Chair: J.H. Woods
Participants will cover one of the most active areas of research interest in the field of neuropsychopharmacology and a field of intense industrial pharmacology development. This session will interest those working on stress and immunology, and the pharmacotherapy of drug abuse.
Regulation and pharmacogenetics of the flavin-containing monooxygenases
Chair: R.N. Hines
The family of flavin-containing monooxygenases (FMOs) plays an important role in the metabolic disposition of numerous therapeutics and environmental toxicants. This symposium will illuminate factors regulating FMO gene expression, our understanding of FMO genetic variation, and how these affect metabolic capacity and disease risk.
Molecular mechanisms and biomarkers of cardiotoxicity
Chair: Y.J. Kang
Cardiotoxicity resulting from therapeutic drugs and exposure to environmental toxicants has been known for a long time. Science is just beginning to understand cellular events and molecular mechanisms of cardiotoxicity. This symposium will provide seminal discussions of cellular events, signaling pathways, and molecular mechanisms of cardiotoxicity, as well as insights into the effect of cardiotoxicological research on the development and validation of biomarkers for diagnosis of cardiac disease and regulation of drug development.
Cellular signaling in 3-D: signaling in space and time
Chair: A. Sorkin
It is increasingly clear that signal transduction pathways interact in exceedingly complex patterns, often with transient interaction of component proteins. An effective means of detecting protein/protein interaction in real time in living cells is Fluorescence Resonance Energy Transfer. This symposium will illustrate the application of these techniques for molecular pharmacologists and include other more traditional methods or alternatives to addressing protein/protein interaction in space or time.
Cytotherapeutics: new approaches for old diseases
Chairs: R. Vulliet and C.R. Freed
Speakers will discuss the treatment of childhood osteogenesis imperfecta with genetically modified bone marrow cells, how bone marrow stem cells generate cardiac myocytes for treatment of myocardial infarction, islet cell transplants for diabetes, and fetal dopamine cell transplantation for Parkinson’s disease.
Drug metabolism platform session: regulation and biotransformation
Chairs: R.N. Hines and R.T. Okita
This platform session will select work that represents cutting-edge work in the areas of biotransformation and/or the regulation of drug metabolizing enzyme expression. Additionally, abstracts representing the two James Gillette Best Paper Awards in the areas of biotransformation and pharmacokinetics also are presented at this session.
Novel aspects of the biology of the Na, K Pump, and digitalis
Chairs: J.C. Allen and A. Askari
It is well known that the NaK pump regulates ion movements in virtually all of mammalian cells, but little is known about how this function is accomplished. This symposium will introduce the newer aspects of pump function (transactivation) and control (cytoplasmic translocation), and their potential relationship to endogenous glycoside function.
Mechanisms of amphetamine in eliciting and regulating monoamine transport
Chairs: A.E. Fleckenstein, M.E. Gnegy and N. Weiner
It has long been established that amphetamine administration increases extracellular monoamine concentrations, and strong evidence suggested that it acted by simple exchange diffusion with internal dopamine. Evidence suggests that amphetamine-induced monoamine release cannot be explained by a simple reversal of the monoamine transporter. Although amphetamines are substrates for the monoamine transporters, they may alter transporter function differently than the physiological monoamine substrates. This symposium will bring together researchers in the field who will share the most current information on the topic.
In vitro vs in vivo measures of efficacy: areas of concordance and discordance
Chair: C.A. Paronis
This symposium will address concordance in the evaluation of efficacy in different pharmacological approaches. The speakers, who will highlight the opioid and dopamine systems, are investigators who work with the same drugs at cellular and behavioral levels of analysis.
Protein therapeutics
Chairs: R.J. Shebuski and C.F. Toombs
