bluuebunny/crossref_metadata_2025 huggingface dataset:
BIOLUMINESCENCE
Authors: Wilson Thérèse , Hastings J. Woodland
Published: July 2002

▪ Abstract  Bioluminescence has evolved independently many times; thus the responsible genes are unrelated in bacteria, unicellular algae, coelenterates, beetles, fishes, and others. Chemically, all involve exergonic reactions of molecular oxygen with different substrates (luciferins) and enzymes (luciferases), resulting in photons of visible light (≈50 kcal). In addition to the structure of luciferan, several factors determine the color of the emissions, such as the amino acid sequence of the luciferase (as in beetles, for example) or the presence of accessory proteins, notably GFP, discovered in coelenterates and now used as a reporter of gene expression and a cellular marker. The mechanisms used to control the intensity and kinetics of luminescence, often emitted as flashes, also vary. Bioluminescence is credited with the discovery of how some bacteria, luminous or not, sense their density and regulate specific genes by chemical communication, as in the fascinating example of symbiosis between luminous bacteria and squid.
The Molecular Basis of Sister-Chromatid Cohesion
Authors: Lee Janice Y. , Orr-Weaver Terry L.
Published: July 2002

▪ Abstract  The replicated copies of each chromosome, the sister chromatids, are attached prior to their segregation in mitosis and meiosis. This association or cohesion is critical for each sister chromatid to bind to microtubules from opposite spindle poles and thus segregate away from each other at anaphase of mitosis or meiosis II. The cohesin protein complex is essential for cohesion in both mitosis and meiosis, and cleavage of one of the subunits is sufficient for loss of cohesion at anaphase. The localization of the cohesin complex and other cohesion proteins permits evaluation of the positions of sister-chromatid associations within the chromosome structure, as well as the relationship between cohesion and condensation. Recently, two key riddles in the mechanism of meiotic chromosome segregation have yielded to molecular answers. First, analysis of the cohesin complex in meiosis provides molecular support for the long-standing hypothesis that sister-chromatid cohesion links homologs in meiosis I by stabilizing chiasmata. Second, the isolation of the monopolin protein that controls kinetochore behavior in meiosis I defines a functional basis by which sister kinetochores are directed toward the same pole in meiosis I.
THE IMPORTANCE OF PĀHOEHOE
Authors: Self S. , Keszthelyi L. , Thordarson Th.
Published: July 2002

▪ Abstract  Pahoehoe lava flows are common in every basaltic province, and their submarine variants, pillow lavas and sheet flows, cover the bulk of the Earth. Pahoehoe flows are emplaced by inflation—the injection of molten lava underneath a solidified crust. Only in the past few years has an understanding of the inflation process and the ability to recognize ancient inflated lava flows been achieved. All large terrestrial basaltic flow fields studied to date, including flood basalts, were emplaced as thermally efficient, inflated, compound pahoehoe sheet flows. This leads us to propose that this is the standard way of emplacing large lavas (the SWELL hypothesis). The atmospheric impact of such flood basalt eruptions could have been protracted and severe, providing a plausible link between flood basalt eruptions and mass extinctions.
Species Richness of Parasite Assemblages: Evolution and Patterns
Authors: Poulin Robert
Published: July 2002

Parasite communities are arranged into hierarchical levels of organization, covering various spatial and temporal scales. These range from all parasites within an individual host to all parasites exploiting a host species across its geographic range. This arrangement provides an opportunity for the study of patterns and structuring processes operating at different scales. Across the parasite faunas of various host species, several species-area relationships have been published, emphasizing the key role of factors such as host size or host geographical range in determining parasite species richness. When corrections are made for unequal sampling effort or phylogenetic influences, however, the strength of these relationships is greatly reduced, casting a doubt over their validity. Component parasite communities, or the parasites found in a host population, are subsets of the parasite fauna of the host species. They often form saturated communities, such that their richness is not always a reflection of that of the entire parasite fauna. The species richness of component communities is instead influenced by the local availability of parasite species and their probability of colonization. At the lowest level, infracommunities in individual hosts are subsets of the species occurring in the component community. Generally, their structure does not differ from that expected from a random assembly of available species, although comparisons with precise null models are still few. Overall studies of parasite communities suggest that the action of processes determining species richness of parasite assemblages becomes less detectable as focus shifts from parasite faunas to infracommunities.
Choosing the Appropriate Scale of Reserves for Conservation
Authors: Schwartz Mark W.
Published: July 2002

▪ Abstract  Over the past ten years the scientific basis for reserve selection and design have rapidly developed. This period has also been characterized by a shift in emphasis toward large spatial and organizational scales of conservation efforts. I discuss the evidence in support of this shift toward larger scale conservation by contrasting the success of fine-filter (genes, populations, species) conservation and coarse-filter (communities, habitats, ecosystems, landscapes) conservation. Conservation at both organizational scales has been successful and merits continued support, although fine-filter conservation is more straightforward. Ecological theory suggests that conservation at large scales is preferred. Despite this preference, both fine- and coarse-filter conservation objectives have been met by small reserves. In many landscapes there are no opportunities for the conservation of native species diversity that encompass a large spatial scale. Thus, reserve selection at any organizational scale may include conservation at a variety of spatial scales. A variety of methods have been suggested that integrate across scales of conservation. Some, such as umbrella, flagship, and indicator species, remain very problematic. Reserve selection algorithms and gap analyses, in contrast, offer promising opportunities to increase the efficiency of conservation at all scales.
The Development and Evolution of Exaggerated Morphologies in Insects
Authors: Emlen Douglas J. , Nijhout H. Frederik
Published: July 2002

▪ Abstract  We discuss a framework for studying the evolution of morphology in insects, based on the concepts of “phenotypic plasticity” and “reaction norms.” We illustrate this approach with the evolution of some of the most extreme morphologies in insects: exaggerated, sexually selected male ornaments and weapons, and elaborate social insect soldier castes. Most of these traits scale with body size, and these scaling relationships are often nonlinear. We argue that scaling relationships are best viewed as reaction norms, and that the evolution of exaggerated morphological traits results from genetic changes in the slope and/or shape of these scaling relationships. After reviewing literature on sexually selected and caste-specific structures, we suggest two possible routes to the evolution of exaggerated trait dimensions: (a) the evolution of steeper scaling relationship slopes and (b) the evolution of sigmoid or discontinuous scaling relationship shapes. We discuss evolutionary implications of these two routes to exaggeration and suggest why so many of the most exaggerated insect structures scale nonlinearly with body size. Finally, we review literature on insect development to provide a comprehensive picture of how scaling relationships arise and to suggest how they may be modified through evolution.
Biochemistry and Genetics of Insect Resistance to Bacillus thuringiensis
Authors: Ferré Juan , Van Rie Jeroen
Published: July 2002

▪ Abstract  Bacillus thuringiensis (Bt) is a valuable source of insecticidal proteins for use in conventional sprayable formulations and in transgenic crops, and it is the most promising alternative to synthetic insecticides. However, evolution of resistance in insect populations is a serious threat to this technology. So far, only one insect species has evolved significant levels of resistance in the field, but laboratory selection experiments have shown the high potential of other species to evolve resistance against Bt. We have reviewed the current knowledge on the biochemical mechanisms and genetics of resistance to Bt products and insecticidal crystal proteins. The understanding of the biochemical and genetic basis of resistance to Bt can help design appropriate management tactics to delay or reduce the evolution of resistance in insect populations.
Sympatric Speciation in Phytophagous Insects: Moving Beyond Controversy?
Authors: Berlocher Stewart H. , Feder Jeffrey L.
Published: July 2002

▪ Abstract  Sympatric speciation is the splitting of one evolutionary lineage into two without the occurrence of geographic isolation. The concept has been intimately tied to entomology since the 1860s, when Benjamin Walsh proposed that many host-specific phytophagous insects originate by shifting and adapting to new host plant species. If true, sympatric speciation would have tremendous implications for our understanding of species and their origins, biodiversity (25–40% of all animals are thought to be phytophagous specialists), insect-plant coevolution, community ecology, phylogenetics, and systematics, as well as practical significance for the management of insect pests. During much of the twentieth century sympatric speciation was viewed as much less plausible than geographic (allopatric) speciation. However, empirical field studies, laboratory experiments, developments in population genetics theory, and phylogenetic and biogeographic data have all recently combined to shed a more favorable light on the process. We review the evidence for sympatric speciation via host shifting for phytophagous insects and propose a set of testable predictions for distinguishing geographic mode (allopatric versus sympatric) of divergence. Our conclusion is that sympatric speciation is a viable hypothesis. We highlight areas where more thorough testing is needed to move sympatric speciation into the realm of accepted scientific theory.
ELLIPTICALINSTABILITY
Authors: Kerswell Richard R.
Published: July 2002

▪ Abstract  In this review we describe the discovery and development of understanding of the so-called elliptical instability. This is the name given to the linear instability mechanism that tends to break up regions of elliptical streamlines in a rotating flow. The instability is discussed in the three different contexts—an unbounded strained vortex, a localized strained vortex, and a triaxial ellipsoid—where it was originally discovered and then rediscovered. These make it clear that the instability is one of parametric resonance where a normal mode, or pair of normal modes, of the undistorted rotating flow resonates with the underlying strain field. The effects of additional physics on the instability process are examined before its nonlinear evolution is discussed. Various applications of the instability in nature are then reviewed.
ONE-POINT CLOSURE MODELS FOR BUOYANCY-DRIVEN TURBULENT FLOWS
Authors: Hanjalić K.
Published: July 2002

▪ Abstract  Turbulent flows driven by thermal buoyancy are featured by phenomena that pose a special challenge to conventional one-point closure models. Inherent unsteadiness, energy nonequilibrium, counter-gradient diffusion, strong pressure fluctuations, and lack of universal scaling, all believed to be associated with distinct large-scale coherent eddy structures, are hardly tractable by Reynolds-type averaging. Second-moment closures, though inadequate for providing information on eddy structure, offer better prospects than eddy-viscosity models for capturing at least some of the phenomena. For some configurations (e.g., with heating from below), unsteady computational solutions of ensemble-averaged equations, using a one-point closure as the subscale model, may be unavoidable for accurate prediction of flow details and wall heat transfer. This article reviews the rationale and some specific modeling issues related to buoyant flows within the realm of one-point closures. The inadequacy of isotropic eddy-diffusivity models is discussed first, followed by the rationale of the second-moment modeling and its term-by-term scrutiny based on direct numerical simulations (DNS). Algebraic models based on a rational truncation of the differential second-moment closure are proposed as the minimum closure level for complex flows. These closures are also recommended as subscale models for transient statistical modeling (T-RANS) and very large eddy simulations (VLES). Examples of applications illustrate some recent achievements.
The Genetic Architecture of Quantitative Traits
Authors: Mackay Trudy F. C.
Published: July 2002

▪ Abstract  Phenotypic variation for quantitative traits results from the segregation of alleles at multiple quantitative trait loci (QTL) with effects that are sensitive to the genetic, sexual, and external environments. Major challenges for biology in the post-genome era are to map the molecular polymorphisms responsible for variation in medically, agriculturally, and evolutionarily important complex traits; and to determine their gene frequencies and their homozygous, heterozygous, epistatic, and pleiotropic effects in multiple environments. The ease with which QTL can be mapped to genomic intervals bounded by molecular markers belies the difficulty in matching the QTL to a genetic locus. The latter requires high-resolution recombination or linkage disequilibrium mapping to nominate putative candidate genes, followed by genetic and/or functional complementation and gene expression analyses. Complete genome sequences and improved technologies for polymorphism detection will greatly advance the genetic dissection of quantitative traits in model organisms, which will open avenues for exploration of homologous QTL in related taxa.
SALMONELLOSIS: Host Immune Responses and Bacterial Virulence Determinants1
Authors: Jones Bradley D. , Falkow Stanley
Published: July 2002

▪ Abstract  The lifestyle of bacterial pathogens requires them to establish infection in the face of host immunity. Upon entering a potential host, a variety of interactions are initiated, the outcome of which depends upon a myriad of attributes of each of the participants. In this review we discuss the interactions that occur between pathogenic Salmonella species and the host immune systems, but when appropriate to broaden perspective, we have provided a general overview of the interactions between bacterial pathogens and animal hosts. Pathogenic Salmonella species possess an array of invasion genes that produce proteins secreted by a specialized type III secretion apparatus. These proteins are used by the bacteria to penetrate the intestinal mucosa by invading and destroying specialized epithelial M cells of the Peyer's patches. This manuever deposits the bacteria directly within the confines of the reticuloendothelial system. The host responds to these actions with nonspecific phagocytic cells and an imflammatory response as well as by activating specific cellular and humoral immune responses. Salmonella responds to this show of force directly. It appears that the bacteria invade and establish a niche within the very cells that have been sent to destroy them. Efforts are underway to characterize the factors that allow these intracellular bacteria to customize intracellular vacuoles for their own purposes. It is the constant play between these interactions that determines the outcome of the host infection, and clearly they will also shape the evolution of new survival strategies for both the bacterium and the host.
CYTOKINE REGULATION OF HOST DEFENSE AGAINST PARASITIC GASTROINTESTINAL NEMATODES:Lessons from Studies with Rodent Models*
Authors: Finkelman Fred D. , Shea-Donohue Terez , Goldhill Jon , Sullivan Carolyn A. , Morris Suzanne C. , Madden Kathleen B. , Gause William C. , Urban Joseph F.
Published: July 2002

▪ Abstract  Studies with rodents infected with Trichinella spiralis, Heligmosomoides polygyrus, Nippostrongylus brasiliensis, and Trichuris muris have provided considerable information about immune mechanisms that protect against parasitic gastrointestinal nematodes. Four generalizations can be made: 1. CD4+T cells are critical for host protection; 2. IL-12 and IFN-γ inhibit protective immunity; 3. IL-4 can: (a) be required for host protection, (b) limit severity of infection, or (c) induce redundant protective mechanisms; and 4. Some cytokines that are stereotypically produced in response to gastrointestinal nematode infections fail to enhance host protection against some of the parasites that elicit their production. Host protection is redundant at two levels: 1. IL-4 has multiple effects on the immune system and on gut physiology (discussed in this review), more than one of which may protect against a particular parasite; and 2. IL-4 is often only one of multiple stimuli that can induce protection. Hosts may have evolved the ability to recognize features that characterize parasitic gastrointestinal nematodes as a class as triggers for a stereotypic cytokine response, but not the ability to distinguish features of individual parasites as stimuli for more specific protective cytokine responses. As a result, hosts deploy a set of defense mechanisms against these parasites that together control infection by most members of that class, even though a specific defense mechanism may not be required to defend against a particular parasite and may even damage a host infected with that parasite.
HOW DO MONOCLONAL ANTIBODIES INDUCE TOLERANCE? A Role for Infectious Tolerance?
Authors: Waldmann Herman , Cobbold Stephen
Published: July 2002

▪ Abstract  One of the major goals in therapeutic immunosuppression has been to achieve long-term benefit from short-term therapy. The discovery in the mid-1980s that CD4 antibodies can induce immunological tolerance without depleting CD4+T cells has reawakened interest in the use of nondepleting monoclonal antibodies for reprogramming the immune system in autoimmunity and in transplantation. Since that time, antibodies to CD11a, CD4OL, CD25, CD3, and CTLA4-Ig have all been shown capable of facilitating tolerance. In order to apply the principle of reprogramming in the clinic, we have sought to understand the mechanisms that are involved in its induction and its maintenance. In a number of allogeneic transplant models (heart, skin, bone marrow) anti-CD4 (± CD8) antibodies can be shown to block the rejection process while selectively promoting the development of CD4+regulatory T cells responsible for a dominant tolerance that is reflected in findings of linked suppression and infectious tolerance. In these models, T cells that have never been exposed to CD4 antibodies become tolerant to grafted antigens by experiencing antigen in the microenvironment of regulatory T cells. Dominant tolerance is not the only mechanism that can be facilitated by CD4 Mab therapy. If allogeneic marrow is given at high cell doses under the umbrella of CD4 and CD8 antibodies, then tolerance can be achieved through clonal deletion.

The mechanism by which regulatory CD4+T cells suppress is not yet defined but could be active or passive. We have proposed the “civil service model” to explain how tolerant T cells might interfere with the responses of competent T cells in such a way as to render them tolerant.

The application of dominant infectious tolerance and linked suppression to clinical immunosuppression should not be underestimated because it suggests that tolerance acquired (through therapy) to a limited set of antigens can spread to embrace all others in the tissues under attack.
THE HIGH-AFFINITY IgE RECEPTOR (FcεRI): From Physiology to Pathology
Authors: Kinet Jean-Pierre
Published: July 2002

▪ Abstract  The high affinity receptor for immunoglobulin E (designated FcεRI) is the member of the antigen (Ag) receptor superfamily responsible for linking pathogen- or allergen-specific IgEs with cellular immunologic effector functions. This review provides background information on FcεRI function combined with more detailed summaries of recent progress in understanding specific aspects of FcεRI biology and biochemistry. Topics covered include the coordination and function of the large multiprotein signaling complexes that are assembled when FcεRI and other Ag receptors are engaged, new information on human receptor structures and tissue distribution, and the role of the FcRβ chain in signaling and its potential contribution to atopic phenotypes.
Interaction of Heat Shock Proteins with Peptides and Antigen Presenting Cells: Chaperoning of the Innate and Adaptive Immune Responses
Authors: Srivastava Pramod
Published: July 2002

Heat shock proteins are abundant soluble intracellular proteins, present in all cells. Members of the heat shock protein family bind peptides including antigenic peptides generated within cells. Heat shock proteins also interact with antigen presenting cells through CD91 and other receptors, eliciting a cascade of events including re-presentation of heat shock protein-chaperoned peptides by MHC, translocation of NFκB into the nuclei and maturation of dendritic cells. These consequences point to a key role of heat shock proteins in fundamental immunological phenomena such as activation of antigen presenting cells, indirect presentation (or cross-priming), and chaperoning of peptides during antigen presentation. Heat shock proteins appear to have been involved in innate immune responses since the emergence of phagocytes in early multicellular organisms and to have been commandeered for adaptive immune responses with the advent of specificity. These properties of heat shock proteins also allow them to be used for immunotherapy of cancers and infections in novel ways.
Device Innovation and Material Challenges at the Limits of CMOS Technology
Authors: Solomon P. M.
Published: July 2002

▪ Abstract  Scaling of the predominant silicon complementary metal-oxide semiconductor (CMOS) technology is finally approaching an end after decades of exponential growth. This review explores the reasons for this limit and some of the strategies available to the semiconductor industry to continue the technology extension. Evolutionary change to the silicon transistor will be pursued as long as possible, with increasing demands being placed on materials. Eventually new materials such a silicon-germanium may be used, and new device topologies such as the double-gated transistor may be employed. These strategies are being pursued in research organizations today. It is likely that planar technology will reach its limit with devices on the 10-nm scale, and then the third dimension will have to be exploited more efficiently to achieve further performance and density improvements.
ANTIDEPRESSANTS IN LONG-TERM TREATMENT
Authors: Montgomery, M.D Stuart A.
Published: July 2002

▪ Abstract  One of the most important recent developments in the management of depression is the recognition of the need for long-term treatment. Treatment of an episode of depression must continue after apparent response in order to consolidate response and prevent relapse. A continuation treatment period of at least four months after response of the acute episode is required in all patients with depression. Most depression is recurrent, and prophylactic treatment with antidepressants reduces the risk of new episodes. This treatment needs to be continued over very long periods, because the risk of new episodes does not appear to diminish with time.

In selecting an antidepressant for long-term treatment efficacy, safety and tolerability in the long term should be taken into account since not all antidepressants have been adequately tested, and some do not appear to be effective. The most thoroughly tested antidepressants are the tricyclic imipramine and the new selective serotonin reuptake inhibitors.
Exercise, Glucose Transport, and Insulin Sensitivity
Authors: Goodyear Laurie J. , Kahn Barbara B.
Published: July 2002

Physical exercise can be an important adjunct in the treatment of both non–insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus. Over the past several years, considerable progress has been made in understanding the molecular basis for these clinically important effects of physical exercise. Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of GLUT4 glucose transporters to the plasma membrane and transverse tubules. Exercise and insulin utilize different signaling pathways, both of which lead to the activation of glucose transport, which perhaps explains why humans with insulin resistance can increase muscle glucose transport in response to an acute bout of exercise. Exercise training in humans results in numerous beneficial adaptations in skeletal muscles, including an increase in GLUT4 expression. The increase in muscle GLUT4 in trained individuals contributes to an increase in the responsiveness of muscle glucose uptake to insulin, although not all studies show that exercise training in patients with diabetes improves overall glucose control. However, there is now extensive epidemiological evidence demonstrating that long-term regular physical exercise can significantly reduce the risk of developing non–insulin-dependent diabetes mellitus.
Screening for Prostate Cancer: The Roles of Science, Policy, and Opinion in Determining What is Best for Patients
Authors: Woolf, MD, MPH Steven H. , Rothemich, MD Stephen F.
Published: July 2002

Controversy over screening for prostate cancer involves both scientific and policy considerations. The principal scientific questions are whether tumors detected by screening are clinically significant, whether screening generates too many false-positive results, and whether early detection lowers morbidity or mortality. Both screening and treatment of prostate cancer can be harmful, making the tradeoff between benefits and risks especially relevant. Studies suggest that this judgment is highly personal, depending on the relative importance that individuals assign to potential outcomes. Opinions and policy considerations also influence views about the appropriateness of screening. Chief among these are personal beliefs about benefits and harms, medicolegal concerns, patient expectations, resource constraints, and opportunity costs. Appropriate policy must discriminate between what is best for populations and for individual patients. The lack of evidence of benefit and the potential harms argue against a societal policy of routine screening. Individual patients who could benefit from screening should be informed about the potential benefits and harms and invited to make a personal choice based on their priorities and concerns.
Salmonella: A Model for Bacterial Pathogenesis
Authors: Ohl Michael E. , Miller Samuel I.
Published: July 2002

▪ Abstract  Salmonellae are gram-negative bacteria that cause gastroenteritis and enteric fever. Salmonella virulence requires the coordinated expression of complex arrays of virulence factors that allow the bacterium to evade the host's immune system. All Salmonella serotypes share the ability to invade the host by inducing their own uptake into cells of the intestinal epithelium. In addition, Salmonella serotypes associated with gastroenteritis orchestrate an intestinal inflammatory and secretory response, whereas serotypes that cause enteric fever establish systemic infection through their ability to survive and replicate in mononuclear phagocytes. This review explores the molecular basis of selected Salmonella virulence strategies, with an emphasis on general themes of bacterial pathogenesis as exemplified by Salmonella.
Multiple Sclerosis
Authors: Keegan B. Mark , Noseworthy John H.
Published: July 2002

▪ Abstract  Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system (CNS). Diagnosis rests upon identifying typical clinical symptoms and interpreting supportive laboratory and radiological investigations. The etiology is unknown; however, strong evidence suggests that MS is an autoimmune disease directed against CNS myelin or oligodendrocytes. Genetic factors are important in the development of MS. Contributing environmental determinants (possibly including infectious agents) appear important but remain unidentified. Both cell-mediated and humorally mediated immune mechanisms contribute to pathological injury. Axonal damage occurs in addition to demyelination and may be the cause of later permanent disability. Distinct pathological subtypes may differentiate among patients with MS. Treatment is directed at acute attacks (with corticosteroids) and reduction of attack frequency (primarily with type-1 β interferons and glatiramer acetate). Research into the causes and treatments of MS has expanded our knowledge of this disease and promises improved care for MS patients in the future.
THE ROLE OF NUCLEIC ACID AMPLIFICATION AND DETECTION IN THE CLINICAL MICROBIOLOGY LABORATORY
Authors: Whelen A. Christian , Persing David H.
Published: July 2002

Clinical microbiology is in the midst of a new era. Methodology that is based on nucleic acid detection has slowly appeared in the diagnostic laboratory, and is revolutionizing our ability to assist physicians in the diagnosis and management of patients suffering from infectious diseases. Much like the introduction of immunoassays built around hybridoma technology in the 1980s, considerable doubt and promise exist hand in hand in the 1990s. Conventional testing that is technically straight forward, informative, and timely will always be a part of clinical microbiology; however, considerable room for improvement exists with organisms/diseases for which laboratory methods are limited. Nucleic acid methodology will have its greatest and long-awaited impact in this arena.
Sequential Organization of Multiple Movements: Involvement of Cortical Motor Areas
Authors: Tanji Jun
Published: July 2002

▪ Abstract  Much of our normal behavior depends on the sequential execution of multiphased movements, or the execution of multiple movements arranged in a correct temporal order. This article deals with the issue of motor selection to arrange multiple movements in an appropriate temporal order, rather than the issue of constructing spatio-temporal structures in a single action. Planning, generating, and controlling the sequential motor behavior involves multiple cortical and subcortical neural structures. Studies on human subjects and nonhuman primates, however, have revealed that the medial motor areas in the frontal cortex and the basal ganglia play particularly important roles in the temporal sequencing of multiple movements. Cellular activity observed in the supplementary and presupplementary motor areas while performing specifically designed motor tasks suggests the way in which these areas take part in constructing the time structure for the sequential execution of multiple movements.
Activity-Dependent Spinal Cord Plasticity in Health and Disease
Authors: Wolpaw Jonathan R , Tennissen Ann M
Published: July 2002

▪ Abstract  Activity-dependent plasticity occurs in the spinal cord throughout life. Driven by input from the periphery and the brain, this plasticity plays an important role in the acquisition and maintenance of motor skills and in the effects of spinal cord injury and other central nervous system disorders. The responses of the isolated spinal cord to sensory input display sensitization, long-term potentiation, and related phenomena that contribute to chronic pain syndromes; they can also be modified by both classical and operant conditioning protocols. In animals with transected spinal cords and in humans with spinal cord injuries, treadmill training gradually modifies the spinal cord so as to improve performance. These adaptations by the isolated spinal cord are specific to the training regimen and underlie new approaches to restoring function after spinal cord injury. Descending inputs from the brain that occur during normal development, as a result of supraspinal trauma, and during skill acquisition change the spinal cord. The early development of adult spinal cord reflex patterns is driven by descending activity; disorders that disrupt descending activity later in life gradually change spinal cord reflexes. Athletic training, such as that undertaken by ballet dancers, is associated with gradual alterations in spinal reflexes that appear to contribute to skill acquisition. Operant conditioning protocols in animals and humans can produce comparable reflex changes and are associated with functional and structural plasticity in the spinal cord, including changes in motoneuron firing threshold and axonal conduction velocity, and in synaptic terminals on motoneurons. The corticospinal tract has a key role in producing this plasticity. Behavioral changes produced by practice or injury reflect the combination of plasticity at multiple spinal cord and supraspinal sites. Plasticity at multiple sites is both necessary—to insure continued performance of previously acquired behaviors—and inevitable—due to the ubiquity of the capacity for activity-dependent plasticity in the central nervous system. Appropriate induction and guidance of activity-dependent plasticity in the spinal cord is an essential component of new therapeutic approaches aimed at maximizing function after spinal cord injury or restoring function to a newly regenerated spinal cord. Because plasticity in the spinal cord contributes to skill acquisition and because the spinal cord is relatively simple and accessible, this plasticity is a logical and practical starting point for studying the acquisition and maintenance of skilled behaviors.
THECOSMICMICROWAVEBACKGROUND ANDPARTICLEPHYSICS
Authors: Kamionkowski Marc , Kosowsky Arthur
Published: July 2002

▪ Abstract  In forthcoming years, connections between cosmology and particle physics will become increasingly important with the advent of a new generation of cosmic microwave background (CMB) experiments. Here, we review a number of these links. Our primary focus is on new CMB tests of inflation. We explain how the inflationary predictions for the geometry of the Universe and primordial density perturbations will be tested by CMB temperature fluctuations, and how the gravitational waves predicted by inflation can be pursued with the CMB polarization. The CMB signatures of topological defects and primordial magnetic fields from cosmological phase transitions are also discussed. Furthermore, we review current and future CMB constraints on various types of dark matter (e.g. massive neutrinos, weakly interacting massive particles, axions, vacuum energy), decaying particles, the baryon asymmetry of the Universe, ultra-high-energy cosmic rays, exotic cosmological topologies, and other new physics.
Random Matrix Theory and Chiral Symmetry in QCD
Authors: Verbaarschot J.J.M. , Wettig T.
Published: July 2002

▪ Abstract  Random matrix theory is a powerful way to describe universal correlations of eigenvalues of complex systems. It also may serve as a schematic model for disorder in quantum systems. In this review, we discuss both types of applications of chiral random matrix theory to the QCD partition function. We show that constraints imposed by chiral symmetry and its spontaneous breaking determine the structure of low-energy effective partition functions for the Dirac spectrum. We thus derive exact results for the low-lying eigenvalues of the QCD Dirac operator. We argue that the statistical properties of these eigenvalues are universal and can be described by a random matrix theory with the global symmetries of the QCD partition function. The total number of such eigenvalues increases with the square root of the Euclidean four-volume. The spectral density for larger eigenvalues (but still well below a typical hadronic mass scale) also follows from the same low-energy effective partition function. The validity of the random matrix approach has been confirmed by many lattice QCD simulations in a wide parameter range. Stimulated by the success of the chiral random matrix theory in the description of universal properties of the Dirac eigenvalues, the random matrix model is extended to nonzero temperature and chemical potential. In this way we obtain qualitative results for the QCD phase diagram and the spectrum of the QCD Dirac operator. We discuss the nature of the quenched approximation and analyze quenched Dirac spectra at nonzero baryon density in terms of an effective partition function. Relations with other fields are also discussed.
THE MAMMALIAN LOW-DENSITY LIPOPROTEIN RECEPTOR FAMILY
Authors: Hussain M. Mahmood , Strickland Dudley K. , Bakillah Ahmed
Published: July 2002

▪ Abstract  The low-density lipoprotein (LDL) receptor (LDL-R) family consists of cell-surface receptors that recognize extracellular ligands and internalize them for degradation by lysosomes. The LDL-R is the prototype of this family, which also contains very-low-density lipoprotein receptors (VLDL-R), apolipoprotein E receptor 2, LRP, and megalin. The family members contain four major structural modules: the cysteine-rich complement-type repeats, epidermal growth factor precursor-like repeats, a transmembrane domain, and a cytoplasmic domain. Each structural module serves distinct and important functions. These receptors bind several structurally dissimilar ligands. It is proposed that instead of a primary sequence, positive electrostatic potential in different ligands constitutes a receptor binding domain. This family of receptors plays crucial roles in various physiologic functions. LDL-R plays an important role in cholesterol homeostasis. Mutations cause familial hypercholesterolemia and premature coronary artery disease. LDL-R–related protein plays an important role in the clearance of plasma-activated α2-macroglobulin and apolipoprotein E–enriched lipoproteins. It is essential for fetal development and has been associated with Alzheimer's disease. Megalin is the major receptor in absorptive epithelial cells of the proximal tubules and an antigenic determinant for Heymann nephritis in rats. Mutations in a chicken homolog of VLDL-R cause female sterility and premature atherosclerosis. This receptor is not expressed in liver tissue; however, transgenic expression of VLDL-R in liver corrects hypercholesterolemia in experiment animals, which suggests that it can be a candidate for gene therapy for various hyperlipidemias. The functional importance of individual receptors may lie in their differential tissue expression. The regulation of expression of these receptors occurs at the transcriptional level. Expression of the LDL-R is regulated by intracellular sterol levels involving novel membrane-bound transcription factors. Other members of the family are not regulated by sterols. All the members are, however, regulated by hormones and growth factors, but the mechanisms of regulation by hormones have not been elucidated. Studies of these receptors have provided important insights into receptor structure-function and mechanisms of ligand removal and catabolism. It is anticipated that increased knowledge about the LDL-R family members will open new avenues for the treatment of many disorders.
CAROTENOID BIOAVAILABILITY AND BIOCONVERSION
Authors: Yeum Kyung-Jin , Russell Robert M.
Published: July 2002

▪ Abstract  The possible role of carotenoids and their metabolites in disease prevention is far from fully understood, because the bioavailabilities of carotenoids are complicated by multiple factors that affect their absorption, breakdown, transport, and storage. Rapid progress in developing sophisticated methodologies, including use of stable-isotope dilution methods, now allows for an accurate determination of the true vitamin A activity of provitamin A carotenoids. The recent identification of specific enzymes, which catalyze the breakdown of β-carotene as well as nonprovitamin A carotenoids, is providing a better understanding of the functions of carotenoids at the molecular level. The pathways and possible mechanisms of carotenoid breakdown and factors affecting the bioavailability of carotenoids, such as carotenoid type, food matrix, interaction with other carotenoids and other food components, nutritional status, aging, and infection, are discussed in this review.
β-ADRENERGIC RECEPTORS AND RECEPTOR SIGNALING IN HEART FAILURE
Authors: Post Steven R. , Hammond H. Kirk , Insel Paul A.
Published: July 2002

▪ Abstract  Cardiac β-adrenergic receptors, which respond to neuronally released and circulating catecholamines, are important regulators of cardiac function. Congestive heart failure, a common clinical condition, is associated with a number of alterations in the activation and deactivation of β-adrenergic receptor pathways. Studies with failing hearts from humans and animals indicate that such alterations include changes in the expression or function of β-adrenergic receptors, G-proteins, adenylyl cyclases, and G-protein receptor kinases. The net effect of these alterations is the substantial blunting of β-adrenergic receptor-mediated cardiac response. An important unanswered question is whether the loss of cardiac β-adrenergic receptor responsiveness is a contributing cause, or a result, of ventricular dysfunction. Even though this question remains unanswered, the concept of targeting the β-adrenergic pathway in the failing heart is becoming increasingly popular and several new therapeutic strategies are in development.
Glutamatergic Mechanisms in Schizophrenia
Authors: Tsai Guochuan , Coyle Joseph T.
Published: July 2002

Schizophrenia is a chronic, severely disabling brain disorder with symptomatic onset in early adulthood. Typical antipsychotic medications that block dopamine D2 receptors are most effective in treating the psychosis but have limited effects on the negative symptoms and cognitive impairments. Considerable research has demonstrated that noncompetitive NMDA receptor antagonists, the dissociative anaesthetic like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia. Postmortem studies reveal variable alterations in glutamate receptors and their modulators in schizophrenia. Several clinical trials indicate agents that enhance NMDA receptor function via the glycine modulatory site reduce negative and variably improve cognitive function in schizophrenics receiving typical antipsychotics. Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia.
RESEARCH IN RETROSPECT:Some Biograffiti of a Journeyman Chemist
Authors: Fenn John B.
Published: July 2002

Small effusive leaks in vacuum systems, as in Knudsen cells and classical molecular beam machines, are responsible for many contributions to science in the twentieth century. Beginning in the 1950s, big convective leaks have turned out to be even more powerful and versatile investigative tools. Forming supersonic free jets, they have greatly expanded molecular beam methods, become the cornerstone of cluster science and technology, rewritten the book on molecular spectroscopy, and are adding new dimension to mass spectrometry. This account is the story of one man's experiences as a bystander and participant in these developments.
Semiclassical Calculation of Chemical Reaction Dynamics via Wavepacket Correlation Functions
Authors: Tannor David J. , Garashchuk Sophya
Published: July 2002

Calculation of chemical reaction dynamics is central to theoretical chemistry. The majority of calculations use either classical mechanics, which is computationally inexpensive but misses quantum effects, such as tunneling and interference, or quantum mechanics, which is computationally expensive and often conceptually opaque. An appealing middle ground is the use of semiclassical mechanics. Indeed, since the early 1970s there has been great interest in using semiclassical methods to calculate reaction probabilities. However, despite the elegance of classical S-matrix theory, numerical results on even the simplest reactive systems remained out of reach. Recently, with advances both in correlation function formulations of reactive scattering as well as in semiclassical methods, it has become possible for the first time to calculate reaction probabilities semiclassically. The correlation function methods are contrasted with recent flux-based methods, which, although providing somewhat more compact expressions for the cumulative reactive probability, are less compatible with semiclassical implementation.
Variability in the Size, Composition, and Function of Insect Flight Muscles
Authors: Marden James H.
Published: July 2002

▪ Abstract  In order to fly, insects require flight muscles that constitute at least 12 to 16% of their total mass, and flight performance increases as this percentage increases. However, flight muscles are energetically and materially expensive to build and maintain, and investment in flight muscles constrains other aspects of function, particularly female fecundity. This review examines ways in which insects vary the size of their flight muscles, and how variation in the relative size and composition of flight muscles affects flight performance. Sources of variability in flight muscle size and composition include genetic differences within and between species, individual phenotypic responses to environmental stimuli, and maturational changes that occur before and during the adult stage. Insects have evolved a wide variety of ways to adjust flight muscle size and contractile performance in order to meet demands imposed by variation in life history and ecology.
The Renin Angiotensin System and Kidney Development
Authors: Matsusaka Taiji , Miyazaki Yoichi , Ichikawa Iekuni
Published: July 2002

▪ Abstract  When angiotensin II or AT1 receptor is experimentally inhibited during the perinatal period, either by pharmacological intervention or genetic manipulation, the kidney develops with profound structural abnormalities. Most prominent are hypertrophy of arterial vasculatures and atrophy of the papilla. Although the mechanism by which the vascular hypertrophy occurs remains unknown, study of the atrophic papilla gives us a new clue for understanding the physiological role of angiotensin. Mutant mice completely devoid of AT1 receptor fail to develop the renal pelvis and the ureteral peristaltic movement. Normally, angiotensin and AT1 receptor are transiently up-regulated around the renal outlet at birth. Thus angiotensin II induces the peristaltic machinery during the perinatal period in a timely fashion to accommodate the dramatic increase in urine production that occurs during the transition from intra- to extra-uterine life. Further studies revealed that in adult animals angiotensin augments the peristaltic movement when the urinary tract is partially obstructed, thereby protecting the kidney from hydronephrosis. This newly discovered function of angiotensin to protect kidney architecture at the time of urine outflow obstruction is reminiscent of its similar kidney structure-protecting function that is active during arterial blood flow obstruction.