bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of the Major Steps in Botulinum Toxin Action
Authors: Simpson Lance L.
Published: January 2004

Botulinum toxin is a uniquely potent substance synthesized by the organisms Clostridium botulinum, Clostridium baratii, and Clostridium butyricum. This toxin, which acts preferentially on peripheral cholinergic nerve endings to block acetylcholine release, is both an agent that causes disease (i.e., botulism) as well as an agent that can be used to treat disease (e.g., dystonia). The ability of botulinum toxin to produce its effects is largely dependent on its ability to penetrate cellular and intracellular membranes. Thus, toxin that is ingested or inhaled can bind to epithelial cells and be transported to the general circulation. Toxin that reaches peripheral nerve endings binds to the cell surface then penetrates the plasma membrane by receptor-mediated endocytosis and the endosome membrane by pH-induced translocation. Internalized toxin acts in the cytosol as a metalloendoprotease to cleave polypeptides that are essential for exocytosis. This review seeks to identify and characterize all major steps in toxin action, from initial absorption to eventual paralysis of cholinergic transmission.
Membrane Trafficking of G Protein–Coupled Receptors
Authors: Tan Christopher M. , Brady Ashley E. , Nickols Hilary Highfield , Wang Qin , Limbird Lee E.
Published: January 2004

G protein-coupled receptors (GPCRs) modulate diverse physiological and behavioral signaling pathways by virtue of changes in receptor activation and inactivation states. Functional changes in receptor properties include dynamic interactions with regulatory molecules and trafficking to various cellular compartments at various stages of the life cycle of a GPCR. This review focuses on trafficking of GPCRs to the cell surface, stabilization there, and agonist-regulated turnover. GPCR interactions with a variety of newly revealed partners also are reviewed with the intention of provoking further analysis of the relevance of these interactions in GPCR trafficking, signaling, or both. The disease consequences of mislocalization of GPCRs also are described.
Voltage-Gated Sodium Channels and Hyperalgesia
Authors: Lai Josephine , Porreca Frank , Hunter John C. , Gold Michael S.
Published: January 2004

Physiological and pharmacological evidence both have demonstrated a critical role for voltage-gated sodium channels (VGSCs) in many types of chronic pain syndromes because these channels play a fundamental role in the excitability of neurons in the central and peripheral nervous systems. Alterations in function of these channels appear to be intimately linked to hyperexcitability of neurons. Many types of pain appear to reflect neuronal hyperexcitability, and importantly, use-dependent sodium channel blockers are effective in the treatment of many types of chronic pain. This review focuses on the role of VGSCs in the hyperexcitability of sensory primary afferent neurons and their contribution to the inflammatory or neuropathic pain states. The discrete localization of the tetrodotoxin (TTX)-resistant channels, in particular NaV1.8, in the peripheral nerves may provide a novel opportunity for the development of a drug targeted at these channels to achieve efficacious pain relief with an acceptable safety profile.
Neurogenesis in the Adult Brain: New Strategies for Central Nervous System Diseases
Authors: Lie D. Chichung , Song Hongjun , Colamarino Sophia A. , Ming Guo-li , Gage Fred H.
Published: January 2004

New cells are continuously generated from immature proliferating cells throughout adulthood in many organs, thereby contributing to the integrity of the tissue under physiological conditions and to repair following injury. In contrast, repair mechanisms in the adult central nervous system (CNS) have long been thought to be very limited. However, recent findings have clearly demonstrated that in restricted areas of the mammalian brain, new functional neurons are constantly generated from neural stem cells throughout life. Moreover, stem cells with the potential to give rise to new neurons reside in many different regions of the adult CNS. These findings raise the possibility that endogenous neural stem cells can be mobilized to replace dying neurons in neurodegenerative diseases. Indeed, recent reports have provided evidence that, in some injury models, limited neuronal replacement occurs in the CNS. Here, we summarize our current understanding of the mechanisms controlling adult neurogenesis and discuss their implications for the development of new strategies for the treatment of neurodegenerative diseases.
Biochemical Mechanism of Nitroglycerin Action and Tolerance: Is This Old Mystery Solved?
Authors: Fung Ho-Leung
Published: January 2004

Organic nitrates such as nitroglycerin (NTG) have been used as potent vasodilators in medicine for more than a century, but their biochemical mechanisms of action, particularly in relation to tolerance development, are still incompletely defined. Numerous candidate enzymes for NTG metabolism, as well as a multiplicity of tolerance mechanisms, have been proposed in the literature, but a consolidating hypothesis that links these phenomena together has not appeared. Here, we outline a “thionitrate oxidation hypothesis,” which attempts to link nitrate bioactivation and tolerance development in an overall mechanism. We also attempt to compare and contrast the proposed mechanism against existing theories of nitrate action and tolerance. Interactions between organic nitrates, which have been thought of as endothelium-independent agents, and the vascular endothelium and endothelial nitric oxide synthase (eNOS) are also discussed.
Novel Angiogenic Signaling Pathways and Vascular Targets
Authors: Bicknell Roy , Harris Adrian L.
Published: January 2004

Intense investigation into the molecular basis of angiogenesis is rapidly revealing novel signaling pathways involved in the generation of new vasculature. These range from elucidation of the mechanism by which hypoxia initiates expression of a proangiogenic gene repertoire via the hypoxia-inducible transcription factors (HIFs) to molecular pathways involved in extra- and intracellular signaling during new vessel formation. Extracellular pathways include those of the Notch/delta, ephrin/Eph receptor and roundabout/slit families, and intracellular pathway members of the hedgehog and sprouty families. The involvement of these pathways in angiogenesis is discussed, together with some comments on recently identified targets in the vasculature that present new therapeutic opportunities.
β-Adrenergic Receptors and Regulation of Energy Expenditure: A Family Affair
Authors: Robidoux Jacques , Martin Tonya L. , Collins Sheila
Published: January 2004

The family of adrenergic receptors (ARs) expressed in adipocytes includes three sibling βARs and two αAR cousins. Together they profoundly influence the mobilization of stored fatty acids, secretion of fat-cell derived hormones, and the specialized process of nonshivering thermogenesis in brown adipose tissue. The two types of fat cells that compose adipose tissue, brown and white, are structurally and functionally distinct. Studies on the mechanisms by which individual βAR regulates these cell-specific functions have recently uncovered new signal transduction cascades involved in processes traditionally ascribed to adenylyl cyclase/cAMP/protein kinase A system. They illustrate how βAR signaling can orchestrate a coordinated set of intracellular responses for fine control of metabolic balance.
Oxidative Stress, Toxicology, and Pharmacology of CYP2E1
Authors: Caro Andres A. , Cederbaum Arthur I.
Published: January 2004

This review describes some of the biochemical and toxicological properties of CYP2E1, especially as it relates to alcohol metabolism and toxicity and the establishment of human hepatoma HepG2 cell lines that overexpress human CYP2E1. Ethanol, polyunsaturated fatty acids, and iron were found to be cytotoxic in HepG2 cells that overexpress CYP2E1. GSH appears to be essential in protecting HepG2 cells against the CYP2E1-dependent cytotoxicity, and GSH levels were elevated owing to a twofold increase in activity and expression of glutamate cysteine ligase. We suggest that this up-regulation of GSH synthesis was an adaptive response to attenuate CYP2E1-dependent oxidative stress and toxicity. Induction of a state of oxidative stress appears to play a central role in the CYP2E1-dependent cytotoxicity. Mitochondrial membrane potential decreased in the CYP2E1-expressing HepG2 cells, and this decrease shared similar characteristics with the developing toxicity. Alcohol-dependent liver injury is likely to be a multifactorial process involving several mechanisms. We believe that the linkage between CYP2E1-dependent oxidative stress, mitochondrial injury, and GSH homeostasis contribute to the toxic actions of ethanol on the liver.
Protein Sulfenic Acids in Redox Signaling
Authors: Poole Leslie B. , Karplus P. Andrew , Claiborne Al
Published: January 2004

Reactive (low pKa) cysteine residues in proteins are critical components in redox signaling. A particularly reactive and versatile reversibly oxidized form of cysteine, the sulfenic acid (Cys-SOH), has important roles as a catalytic center in enzymes and as a sensor of oxidative and nitrosative stress in enzymes and transcriptional regulators. Depending on environment, sometimes the sulfenic acid provides a metastable oxidized form, and other times it is a fleeting intermediate giving rise to more stable disulfide, sulfinic acid, or sulfenyl-amide forms.
The Role of Calpain in Oncotic Cell Death
Authors: Liu Xiuli , Van Vleet Terry , Schnellmann Rick G.
Published: January 2004

Numerous lines of evidence demonstrate that calpains, a family of 14 Ca2+-activated neutral cysteine proteases, are involved in oncotic cell death in a variety of models. At this time, the biochemistry of most calpains and the specific roles of different calpains in physiology and pathology remain to be determined. A number of calpain substrates have been identified in cellular systems, including cytoskeletal proteins, and recent studies suggest that calpains mediate the increase in plasma membrane permeability to ions and the progressive breakdown of the plasma membrane observed in oncosis through the proteolysis of cystokeletal and plasma membrane proteins. Further, a number of reports provide evidence that the mitochondrial dysfunction observed in oncosis may be mediated by a mitochondrial calpain of unknown identity. Finally, a number of diverse calpain inhibitors have been developed that show cytoprotective properties in cellular systems and in vivo following diverse insults. It is suggested that future research be directed toward elucidation of the role(s) of specific calpain isozymes in physiological and pathological conditions; identifying and linking specific calpain substrates with altered cellular functions; and developing cell-permeable, potent, isozyme-selective calpain inhibitors.
Mixed-Lineage Kinases: A Target for the Prevention of Neurodegeneration
Authors: Wang Leo H. , Besirli Cagri G. , Johnson Eugene M.
Published: January 2004

The activation of the c-Jun N-terminal kinase (JNK) pathway is critical for naturally occurring neuronal cell death during development and may be important for the pathological neuronal cell death of neurodegenerative diseases. The small molecule inhibitor of the mixed-lineage kinase (MLK) family of kinases, CEP-1347, inhibits the activation of the JNK pathway and, consequently, the cell death in many cell culture and animal models of neuronal death. CEP-1347 has the ability not only to inhibit cell death but also to maintain the trophic status of neurons in culture. The possible importance of the JNK pathway in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases provides a rationale for the use of CEP-1347 for the treatment of these diseases. CEP-1347 has the potential of not only retarding disease progression but also reversing the severity of symptoms by improving the function of surviving neurons.
The Role of Oxidative Stress in Carcinogenesis
Authors: Klaunig James E. , Kamendulis Lisa M.
Published: January 2004

Chemical carcinogenesis follows a multistep process involving both mutation and increased cell proliferation. Oxidative stress can occur through overproduction of reactive oxygen and nitrogen species through either endogenous or exogenous insults. Important to carcinogenesis, the unregulated or prolonged production of cellular oxidants has been linked to mutation (induced by oxidant-induced DNA damage), as well as modification of gene expression. In particular, signal transduction pathways, including AP-1 and NFκB, are known to be activated by reactive oxygen species, and they lead to the transcription of genes involved in cell growth regulatory pathways. This review examines the evidence of cellular oxidants' involvement in the carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species.
Transporters and Renal Drug Elimination
Authors: Lee Wooin , Kim Richard B.
Published: January 2004

Carrier-mediated processes, often referred to as transporters, play key roles in the reabsorption and secretion of many endogenous and xenobiotic compounds by the kidney. The renal proximal tubule is the primary site of active transport for a wide variety of substrates, including organic anions/cations, peptides, and nucleosides. During the past decade, significant advances in molecular identification and characterization of transporter proteins have been made. Although it is generally noted that these transporters significantly contribute to renal drug handling and variability in drug disposition, the extent of our knowledge regarding the specific roles of such transporters in drug disposition and drug-drug interactions remains, for the most part, limited. In this review, we summarize recent progress in terms of molecular and functional characterization of renal transporters and their clinical relevance to drug therapy.
The Intergenerational Transfer of Psychosocial Risk: Mediators of Vulnerability and Resilience
Authors: Serbin Lisa A. , Karp Jennifer
Published: January 2004

The recurrence of social, behavioral, and health problems in successive generations of families is a prevalent theme in both the scientific and popular literatures. This review discusses recent conceptual models and findings from longitudinal studies concerning the intergenerational transfer of psychosocial risk, including intergenerational continuity, and the processes whereby a generation of parents may place their offspring at elevated risk for social, behavioral, and health problems. Key findings include the mediational effects of parenting and environmental factors in the transfer of risk. In both girls and boys, childhood aggression and antisocial behavior appear to predict long-term trajectories that place offspring at risk. Sequelae of childhood aggression that may threaten the well-being of offspring include school failure, adolescent risk-taking behavior, early and single parenthood, and family poverty. These childhood and adolescent behavioral styles also predict harsh, aggressive, neglectful, and unstimulating parenting behavior toward offspring. Buffering factors within at-risk families include maternal educational attainment and constructive parenting practices (e.g., emotional warmth, consistent disciplinary practices, and cognitive scaffolding). These findings highlight the potential application and relevance of intergenerational studies for social, educational, and health policy.
Toward an Integrative Science of the Person
Authors: Mischel Walter
Published: January 2004

To build a science of the person, the most basic question was, and remains, how can one identify and understand the psychological invariance that distinctively characterizes an individual and that underlies the variations in the thoughts, feelings, and actions that occur across contexts and over time? This question proved particularly difficult because of the discrepancies that soon emerged between the expressions of consistency that were expected and those that were found. The resulting dilemma became known as the classic “personality paradox”: How can we reconcile our intuitions—and theories—about the invariance and stability of personality with the equally compelling empirical evidence for the variability of the person's behavior across diverse situations? Which is right: the intuitions or the research findings? In this chapter I review and discuss some of the advances made to answer this question since it was posed. These findings have allowed a resolution of the paradox, and provide the outlines for a conception of the underlying structure and dynamics of personality that seems to better account for the data.
Teaching of Subject Matter
Authors: Mayer Richard E.
Published: January 2004

Psychology of subject matter refers to the scientific study of learning and instruction within school subjects. The growing research literature on teaching and learning of school subjects represents one of educational psychology's most productive accomplishments of the past two decades. The purpose of this chapter is to examine representative advances in the psychology of subject matter, including how people learn to read words, comprehend printed passages, write compositions, solve arithmetic word problems, and understand how scientific systems work. The introduction provides a historical overview of how to promote transfer and is followed by reviews of representative research in learning and teaching of reading fluency, reading comprehension, writing, mathematics, and science.
Cumulative Progress in Formal Theories of Attention
Authors: Logan Gordon D.
Published: January 2004

Formal theories of attention based on similarity-choice theory and signal-detection theory are reviewed to document cumulative progress in theoretical understanding of attention from the 1950s to the present. Theories based on these models have been developed to account for a wide variety of attentional phenomena, including attention to dimensions, attention to objects, and executive control. The review describes the classical similarity-choice and signal-detection theories and relates them to current theories of categorization, Garner tasks, visual search, cuing procedures, task switching, and strategy choice.
Coping: Pitfalls and Promise
Authors: Folkman Susan , Moskowitz Judith Tedlie
Published: January 2004

Coping, defined as the thoughts and behaviors used to manage the internal and external demands of situations that are appraised as stressful, has been a focus of research in the social sciences for more than three decades. The dramatic proliferation of coping research has spawned healthy debate and criticism and offered insight into the question of why some individuals fare better than others do when encountering stress in their lives. We briefly review the history of contemporary coping research with adults. We discuss three primary challenges for coping researchers (measurement, nomenclature, and effectiveness), and highlight recent developments in coping theory and research that hold promise for the field, including previously unaddressed aspects of coping, new measurement approaches, and focus on positive affective outcomes.
Creativity
Authors: Runco Mark A.
Published: January 2004

Creativity has clear benefits for individuals and society as a whole. Not surprisingly, a great deal of research has focused on creativity, especially in the past 20 years. This chapter reviews the creativity research, first looking to the relevant traits, capacities, influences, and products, and then within disciplinary perspectives on creativity (e.g., biological, cognitive, developmental, organizational). Great headway is being made in creativity research, but more dialogue between perspectives is suggested. New and important areas of research are highlighted, and the various costs and benefits of creativity are discussed.
Development in Midlife
Authors: Lachman Margie E.
Published: January 2004

The midlife period in the lifespan is characterized by a complex interplay of multiple roles. The goal of this chapter is to summarize research findings on the central themes and salient issues of midlife such as balancing work and family responsibilities in the midst of the physical and psychological changes associated with aging. The field of midlife development is emerging in the context of large demographic shifts in the population. A section on the phenomenology of midlife development presents images and expectations including the seemingly disparate views of midlife as a time of peak functioning and a period of crisis. Conceptual frameworks useful for studying the multiple patterns of change in midlife are presented. Findings demonstrating patterns of gains and losses are reviewed for multiple domains: cognitive functioning, personality and the self, emotions, social relationships, work, and physical health. The need for future research to illuminate and integrate the diverse aspects of midlife is highlighted.
Development in the Family
Authors: Parke Ross D.
Published: January 2004

In this chapter we review theoretical conceptual and empirical advances in family research and the implications for children's development. Three interdependent family subsystems are considered: the parent-child subsystem, the marital subsystem, and the sibling subsystem. Recent work on the family as a unit of analysis is reviewed as well. Several determinants of family socialization strategies are noted, including child and parental characteristics and resources and social capital available to families. Ethnicity is considered by reviewing recent advances in our understanding of African American, Asian American, and Hispanic families. Several new directions in family research are highlighted. These include research on the linkage between families and work, gay and lesbian parenting, the new reproductive technologies, and the effect of parental incarcerations on families. Future trends in family research are noted, including the role of genetics, the biological correlates of family processes, the role of intervention and prevention designs in family research, and the importance of process work on ethnicity-oriented family research.
Gender in Psychology
Authors: Stewart Abigail J. , McDermott Christa
Published: January 2004

Gender is increasingly understood as defining a system of power relations embedded in other power relations. Psychological research on gender—which has most often focused on analysis of sex differences, within-sex variability, and gender roles—has begun to incorporate this new understanding. By drawing on three resources, psychologists can make more rapid progress in understanding gender's significance for psychological processes: social science theories that link the individual and social levels of analysis; constructs (such as identity) that bridge the social and individual levels; and conceptual tools generated in feminist theory, perhaps especially intersectionality. We review these resources, cite active research programs that have employed them, and conclude by offering some practical suggestions about how to incorporate these resources into our research.
Hypocretin (OREXIN): Role in Normal Behavior and Neuropathology
Authors: Siegel Jerome M.
Published: January 2004

The hypocretins (Hcrts, also known as orexins) are two peptides, both synthesized by a small group of neurons, most of which are in the lateral hypothalamic and perifornical regions of the hypothalamus. The hypothalamic Hcrt system directly and strongly innervates and potently excites noradrenergic, dopaminergic, serotonergic, histaminergic, and cholinergic neurons. Hcrt also has a major role in modulating the release of glutamate and other amino acid transmitters. Behavioral investigations have revealed that Hcrt is released at high levels in active waking and rapid eye movement (REM) sleep and at minimal levels in non-REM sleep. Hcrt release in waking is increased markedly during periods of increased motor activity relative to levels in quiet, alert waking. Evidence for a role for Hcrt in food intake regulation is inconsistent. I hypothesize that Hcrt's major role is to facilitate motor activity tonically and phasically in association with motivated behaviors and to coordinate this facilitation with the activation of attentional and sensory systems. Degeneration of Hcrt neurons or genetic mutations that prevent the normal synthesis of Hcrt or of its receptors causes human and animal narcolepsy. Narcolepsy is characterized by an impaired ability to maintain alertness for long periods and by sudden losses of muscle tone (cataplexy). Administration of Hcrt can reverse symptoms of narcolepsy in animals, may be effective in treating human narcolepsy, and may affect a broad range of motivated behaviors.
Mediated Politics and Citizenship in the Twenty-First Century
Authors: Graber Doris
Published: January 2004

Since the birth of the nation, concepts about the political duties of citizens have changed drastically to keep pace with growth and development. The information needs have changed as well, as have the institutions that supply this information. In this essay I analyze the interrelation between citizenship in the twenty-first century and the information supply that nourishes it. I focus on studies that explore how political news is shaped to attract public attention and how citizens select it and make sense of it. Evidence from content analyses, focus group data, and intensive interviews supports the conclusion that the news supply is adequate for citizens' civic needs and that they use it judiciously. To accept that conclusion requires abandoning outdated paradigms of citizenship that ignore information-processing capabilities of human beings, the basic motivations that drive the search for political information, and the impact of the ever-increasing complexity of politics.
The Psychology and Neuroscience of Forgetting
Authors: Wixted John T.
Published: January 2004

Traditional theories of forgetting are wedded to the notion that cue-overload interference procedures (often involving the A-B, A-C list-learning paradigm) capture the most important elements of forgetting in everyday life. However, findings from a century of work in psychology, psychopharmacology, and neuroscience converge on the notion that such procedures may pertain mainly to forgetting in the laboratory and that everyday forgetting is attributable to an altogether different form of interference. According to this idea, recently formed memories that have not yet had a chance to consolidate are vulnerable to the interfering force of mental activity and memory formation (even if the interfering activity is not similar to the previously learned material). This account helps to explain why sleep, alcohol, and benzodiazepines all improve memory for a recently learned list, and it is consistent with recent work on the variables that affect the induction and maintenance of long-term potentiation in the hippocampus.
Visual Mechanisms of Motion Analysis and Motion Perception
Authors: Derrington Andrew M. , Allen Harriet A. , Delicato Louise S.
Published: January 2004

Psychophysical experiments on feature tracking suggest that most of our sensitivity to chromatic motion and to second-order motion depends on feature tracking. There is no reason to suppose that the visual system contains motion sensors dedicated to the analysis of second-order motion. Current psychophysical and physiological data indicate that local motion sensors are selective for orientation and spatial frequency but they do not eliminate any of the three main models—the Reichardt detector, the motion-energy filter, and gradient-based sensors. Both psychophysical and physiological data suggest that both broadly oriented and narrowly oriented motion sensors are important in the early analysis of motion in two dimensions.
On Building a Bridge Between Brain and Behavior
Authors: Schall Jeffrey D.
Published: January 2004

Cognitive neuroscience is motivated by the precept that a discoverable correspondence exists between mental states and brain states. This precept seems to be supported by remarkable observations and conclusions derived from event-related potentials and functional imaging with humans and neurophysiology with behaving monkeys. This review evaluates specific conceptual and technical limits of claims of correspondence between neural events, overt behavior, and hypothesized covert processes examined using data on the neural control of saccadic eye movements.
The Internet and Social Life
Authors: Bargh John A. , McKenna Katelyn Y. A.
Published: January 2004

The Internet is the latest in a series of technological breakthroughs in interpersonal communication, following the telegraph, telephone, radio, and television. It combines innovative features of its predecessors, such as bridging great distances and reaching a mass audience. However, the Internet has novel features as well, most critically the relative anonymity afforded to users and the provision of group venues in which to meet others with similar interests and values. We place the Internet in its historical context, and then examine the effects of Internet use on the user's psychological well-being, the formation and maintenance of personal relationships, group memberships and social identity, the workplace, and community involvement. The evidence suggests that while these effects are largely dependent on the particular goals that users bring to the interaction—such as self-expression, affiliation, or competition—they also interact in important ways with the unique qualities of the Internet communication situation.
Psychology and Culture
Authors: Lehman Darrin R. , Chiu Chi-yue , Schaller Mark
Published: January 2004

Psychological processes influence culture. Culture influences psychological processes. Individual thoughts and actions influence cultural norms and practices as they evolve over time, and these cultural norms and practices influence the thoughts and actions of individuals. Large bodies of literature support these conclusions within the context of research on evolutionary processes, epistemic needs, interpersonal communication, attention, perception, attributional thinking, self-regulation, human agency, self-worth, and contextual activation of cultural paradigms. Cross-cultural research has greatly enriched psychology, and key issues for continued growth and maturation of the field of cultural psychology are articulated.
Schizophrenia: Etiology and Course
Authors: Walker Elaine , Kestler Lisa , Bollini Annie , Hochman Karen M.
Published: January 2004

Decades of research on schizophrenia have not produced major breakthroughs, but gradual progress has been made in identifying risk factors and clarifying the nature of the etiologic process. This article provides an overview of trends in research findings as well as current assumptions about the interplay between environmental and genetic factors in the etiology of schizophrenia. Based on the cumulative findings, it appears that both genetic and prenatal factors can give rise to constitutional vulnerability. Subsequent neuromaturational processes, especially those that occur during adolescence, and exposure to stressful events can trigger the behavioral expression of this vulnerability.
Self-Knowledge: Its Limits, Value, and Potential for Improvement
Authors: Wilson Timothy D. , Dunn Elizabeth W.
Published: January 2004

Because of personal motives and the architecture of the mind, it may be difficult for people to know themselves. People often attempt to block out unwanted thoughts and feelings through conscious suppression and perhaps through unconscious repression, though whether such attempts are successful is controversial. A more common source of self-knowledge failure is the inaccessibility of much of the mind to consciousness, including mental processes involved in perception, motor learning, personality, attitudes, and self-esteem. Introspection cannot provide a direct pipeline to these mental processes, though some types of introspection may help people construct beneficial personal narratives. Other ways of increasing self-knowledge include looking at ourselves through the eyes of others and observing our own behavior. These approaches can potentially promote self-knowledge, although major obstacles exist. It is not always advantageous to hold self-perceptions that correspond perfectly with reality, but increasing awareness of nonconscious motives and personality is generally beneficial.
Object Perception as Bayesian Inference
Authors: Kersten Daniel , Mamassian Pascal , Yuille Alan
Published: January 2004

We perceive the shapes and material properties of objects quickly and reliably despite the complexity and objective ambiguities of natural images. Typical images are highly complex because they consist of many objects embedded in background clutter. Moreover, the image features of an object are extremely variable and ambiguous owing to the effects of projection, occlusion, background clutter, and illumination. The very success of everyday vision implies neural mechanisms, yet to be understood, that discount irrelevant information and organize ambiguous or noisy local image features into objects and surfaces. Recent work in Bayesian theories of visual perception has shown how complexity may be managed and ambiguity resolved through the task-dependent, probabilistic integration of prior object knowledge with image features.
Group Performance and Decision Making
Authors: Kerr Norbert L. , Tindale R. Scott
Published: January 2004

Theory and research on small group performance and decision making is reviewed. Recent trends in group performance research have found that process gains as well as losses are possible, and both are frequently explained by situational and procedural contexts that differentially affect motivation and resource coordination. Research has continued on classic topics (e.g., brainstorming, group goal setting, stress, and group performance) and relatively new areas (e.g., collective induction). Group decision making research has focused on preference combination for continuous response distributions and group information processing. New approaches (e.g., group-level signal detection) and traditional topics (e.g., groupthink) are discussed. New directions, such as nonlinear dynamic systems, evolutionary adaptation, and technological advances, should keep small group research vigorous well into the future.
Social Influence: Compliance and Conformity
Authors: Cialdini Robert B. , Goldstein Noah J.
Published: January 2004

This review covers recent developments in the social influence literature, focusing primarily on compliance and conformity research published between 1997 and 2002. The principles and processes underlying a target's susceptibility to outside influences are considered in light of three goals fundamental to rewarding human functioning. Specifically, targets are motivated to form accurate perceptions of reality and react accordingly, to develop and preserve meaningful social relationships, and to maintain a favorable self-concept. Consistent with the current movement in compliance and conformity research, this review emphasizes the ways in which these goals interact with external forces to engender social influence processes that are subtle, indirect, and outside of awareness.
Speech Perception
Authors: Diehl Randy L. , Lotto Andrew J. , Holt Lori L.
Published: January 2004

This chapter focuses on one of the first steps in comprehending spoken language: How do listeners extract the most fundamental linguistic elements—consonants and vowels, or the distinctive features which compose them—from the acoustic signal? We begin by describing three major theoretical perspectives on the perception of speech. Then we review several lines of research that are relevant to distinguishing these perspectives. The research topics surveyed include categorical perception, phonetic context effects, learning of speech and related nonspeech categories, and the relation between speech perception and production. Finally, we describe challenges facing each of the major theoretical perspectives on speech perception.
Clinical Implications of Reinforcement as a Determinant of Substance Use Disorders
Authors: Higgins Stephen T. , Heil Sarah H. , Lussier Jennifer Plebani
Published: January 2004

Extensive scientific evidence indicates that reinforcement plays an important role in the genesis, maintenance, and recovery from substance use disorders. In this chapter, we review recent clinical research from laboratory, clinic, and naturalistic settings examining the role of reinforcement in substance use disorders. Well-controlled human laboratory studies are reviewed characterizing orderly interactions between the reinforcing effects of drugs and environmental context that have important implications for understanding risk factors for substance use disorders and for the development of efficacious interventions. Recent treatment-outcome studies on voucher-based contingency management and community reinforcement therapy are reviewed demonstrating how reinforcement and related principles can be used to improve outcomes across a wide range of different substance use disorders and populations. Overall, the chapter characterizes a vigorous area of clinical research that has much to contribute to a scientific analysis of substance use disorders.
Survey Research and Societal Change
Authors: Tourangeau Roger
Published: January 2004

Surveys reflect societal change in a way that few other research tools do. Over the past two decades, three developments have transformed surveys. First, survey organizations have adopted new methods for selecting telephone samples; these new methods were made possible by the creation of large databases that include all listed telephone numbers in the United States. A second development has been the widespread decline in response rates for all types of surveys. In the face of this problem, survey researchers have developed new theories of nonresponse that build on the persuasion literature in social psychology. Finally, surveys have adopted many new methods of data collection; the new modes reflect technological developments in computing and the emergence of the Internet. Research has spawned several theories that examine how characteristics of the data collection method shape the answers obtained. Rapid change in survey methods is likely to continue in the coming years.
Understanding Other Minds: Linking Developmental Psychology and Functional Neuroimaging
Authors: Saxe R. , Carey S. , Kanwisher N.
Published: January 2004

Evidence from developmental psychology suggests that understanding other minds constitutes a special domain of cognition with at least two components: an early-developing system for reasoning about goals, perceptions, and emotions, and a later-developing system for representing the contents of beliefs. Neuroimaging reinforces and elaborates upon this view by providing evidence that (a) domain-specific brain regions exist for representing belief contents, (b) these regions are apparently distinct from other regions engaged in reasoning about goals and actions (suggesting that the two developmental stages reflect the emergence of two distinct systems, rather than the elaboration of a single system), and (c) these regions are distinct from brain regions engaged in inhibitory control and in syntactic processing. The clear neural distinction between these processes is evidence that belief attribution is not dependent on either inhibitory control or syntax, but is subserved by a specialized neural system for theory of mind.
The Neurobiology of Consolidations, Or, How Stable is the Engram?
Authors: Dudai Yadin
Published: January 2004

Consolidation is the progressive postacquisition stabilization of long-term memory. The term is commonly used to refer to two types of processes: synaptic consolidation, which is accomplished within the first minutes to hours after learning and occurs in all memory systems studied so far; and system consolidation, which takes much longer, and in which memories that are initially dependent upon the hippocampus undergo reorganization and may become hippocampal-independent. The textbook account of consolidation is that for any item in memory, consolidation starts and ends just once. Recently, a heated debate has been revitalized on whether this is indeed the case, or, alternatively, whether memories become labile and must undergo some form of renewed consolidation every time they are activated. This debate focuses attention on fundamental issues concerning the nature of the memory trace, its maturation, persistence, retrievability, and modifiability.
Mouse Models of Abdominal Aortic Aneurysms
Authors: Daugherty Alan , Cassis Lisa A.
Published: January 2004

Many mouse models of abdominal aortic aneurysms have been developed that use a diverse array of methods for producing the disease, including genetic manipulation and chemical induction. These models could provide insight into potential mechanisms in the development of this disease. Although experimental studies on abdominal aortic aneurysms (AAAs) have used a variety of mammalian and avian approaches, there is an increasing reliance on the use of mice. The models recapitulate some facets of the human disease including medial degeneration, inflammation, thrombus formation, and rupture. Most of the mouse models of AAA are evoked either by genetically defined approaches or by chemical means. The genetic approaches are spontaneous and engineered mutations. These include defects in extracellular matrix maturation, increased degradation of elastin and collagen, aberrant cholesterol homeostasis, and enhanced production of angiotensin peptides. The chemical approaches include the intraluminal infusion of elastase, periaortic incubations of calcium chloride, and subcutaneous infusion of AngII. A common feature of these models is the reduction of AAA incidence and severity by the prophylactic administration of matrix metalloproteinase (MMP) inhibitors or genetically engineered deficiencies of specific members of this proteolytic protein family. The validation of mouse models of AAAs will provide insight into the mechanisms of progression of the human disease.
Deleterious Impact of “High Normal” Glucose Levels and Other Metabolic Syndrome Components on Arterial Endothelial Function and Intima-Media Thickness in Apparently Healthy Chinese Subjects: The CATHAY Study
Authors: Thomas G. Neil , Chook Ping , Qiao Mu , Huang Xin S. , Leong Hok C. , Celermajer David S. , Woo Kam S.
Published: January 2004

Objective—

Endothelial vasodilator dysfunction and carotid intima-media thickening are useful surrogate markers of cardiovascular disease, a major cause of morbidity and mortality in type 2 diabetic patients. However, because most studies reporting the relationships between endothelial function, intima-media thickness (IMT), and hyperglycemia have compared diabetic patients with healthy controls, we report their relationship with glycemia as a continuum.

Methods and Results—

Brachial artery endothelial function (flow-mediated dilatation [FMD]) and carotid IMT were measured noninvasively by high-resolution ultrasound B-mode imaging in 228 apparently healthy Chinese subjects recruited from Hong Kong and Macau. FMD and IMT were significantly associated with increasing levels of glycemia, particularly in the “high normal” glycemic range, with IMT increasing and endothelium-independent dilatation decreasing linearly across the glucose tertiles, and endothelium-dependent dilatation significantly lower in the upper glucose tertile compared with the other 2 groups (
P
<0.01). Using multiple linear regression, fasting glucose level was identified as an independent predictor of each of these markers of vascular function (
P
<0.004). Additionally, other conventional cardiovascular risk factors, including obesity, blood pressure, and an adverse lipid profile, were also related to levels of glycemia (
P
<0.05), further contributing to impaired vascular function.

Conclusion—

Increasing levels of glycemia and the coexistence of other cardiovascular risk factors in apparently healthy subjects are adversely associated with arterial endothelial dysfunction and intima-media thickening.
Role of Bone Marrow–Derived Progenitor Cells in Cuff-Induced Vascular Injury in Mice
Authors: Xu Yang , Arai Hidenori , Zhuge Xin , Sano Hideto , Murayama Toshinori , Yoshimoto Momoko , Heike Toshio , Nakahata Tatsutoshi , Nishikawa Shin-ichi , Kita Toru , Yokode Masayuki
Published: January 2004

Objectives—

Arterial injury results in vascular remodeling associated with proliferation and migration of smooth muscle cells (SMCs) and the development of intimal hyperplasia, which is a critical component of restenosis after angioplasty of human coronary arteries and an important feature of atherosclerotic lesions. However, the origin of SMCs and other cells in the development of vascular remodeling is not yet fully understood.

Methods and Results—

We utilized a cuff-induced vascular injury model after transplantation of the bone marrow (BM) from green fluorescent protein (GFP)-transgenic mice. We found that macrophages were major cells recruited to the adventitia of the vascular injury lesion along with SMCs and endothelial cells (ECs). While investigating whether those cells are derived from the donor, we found that most of the macrophages were GFP-positive, and some of the SMCs and ECs were also GFP-positive. Administration of the anti–c-
fms
antibody resulted in a marked decrease in macrophages and a relative increase of SMCs, while administration of antibodies against the platelet-derived growth factor receptor-β caused a prominent decrease in SMCs and a relative increase in macrophages.

Conclusions—

The current study indicates that BM-derived cells play an important role in vascular injury, and that differentiation of macrophages and SMCs might be dependent on each other.
Monocyte Chemoattractant Protein-1 Is an Essential Inflammatory Mediator in Angiotensin II-Induced Progression of Established Atherosclerosis in Hypercholesterolemic Mice
Authors: Ni Weihua , Kitamoto Shiro , Ishibashi Minako , Usui Makoto , Inoue Shujiro , Hiasa Ken-ichi , Zhao Qingwei , Nishida Ken-ichi , Takeshita Akira , Egashira Kensuke
Published: January 2004

Objective—Chronic inflammatory processes might be involved in the progression and destabilization of atherosclerotic plaques. Therefore, identification of the mechanism underlying arterial inflammatory function might lead to the development of novel therapeutic strategies. Angiotensin II (AngII) is implicated in atherogenesis by activating the vascular inflammation system, mainly through monocyte chemotaxis. Therefore, we hypothesized that AngII increases plaque size and promotes destabilization of established atheromas by activating the monocyte chemoattractant protein-1 (MCP-1) pathway.

Methods and Results—We report here that 4-week infusion of AngII not only increased plaque size but also induced a destabilization phenotype (ie, increased macrophages and lipids and decreased collagen and smooth muscle cells) of pre-existing atherosclerotic lesions of hypercholesterolemic mice. AngII also enhanced the gene expression of inflammatory cytokines (TNFα, IL-6, etc.) and chemokines (MCP-1, CCR2, etc). Blockade of MCP-1, by transfecting the deletion mutant of the human MCP-1 gene into the skeletal muscles, limited AngII-induced progression and destabilization of established atherosclerotic lesions and suppressed the induction of proinflammatory genes.

Conclusions—These data suggest that MCP-1 functions as a central inflammatory mediator in the AngII-induced progression and changes in plaque composition of established atheroma.