bluuebunny/crossref_metadata_2025 huggingface dataset:
WILL THE REAL AGENT OF CAT-SCRATCH DISEASE PLEASE STAND UP?
Authors: Jerris Robert C. , Regnery Russell L.
Published: July 2002

Cat-scratch disease has been recognized since 1889 in association with the oculoglandular syndrome of Parinaud. The epidemiologic association with cats was first made in 1931 and further substantiated throughout the years, refining the interaction predominantly to kittens. Putative infectious agents have included numerous species of bacteria, chlamydiae, and viruses. The cultivation of Afipia spp. in the late 1980s appeared to answer the mystery of the identity of the agent. However, even more recent analysis, which has combined traditional microbiology, molecular methods, and additional epidemiology, has demonstrated that Bartonella (Rochalimaea) henselae is the definitive agent of cat-scratch disease. Our understanding of the pathogenesis of cat-scratch disease and other diseases caused by Bartonella species is incomplete and the spectrum of diseases continues to emerge. We review historic and modern efforts to understand the etiology of cat-scratch disease and related syndromes.
CLUES AND CONSEQUENCES OF DNA BENDING IN TRANSCRIPTION
Authors: Pérez-Martín José , de Lorenzo Víctor
Published: July 2002

▪ Abstract  This review attempts to substantiate the notion that nonlinear DNA structures allow prokaryotic cells to evolve complex signal integration devices that, to some extent, parallel the transduction cascades employed by higher organisms to control cell growth and differentiation. Regulatory cascades allow the possibility of inserting additional checks, either positive or negative, in every step of the process. In this context, the major consequence of DNA bending in transcription is that promoter geometry becomes a key regulatory element. By using DNA bending, bacteria afford multiple metabolic control levels simply through alteration of promoter architecture, so that positive signals favor an optimal constellation of protein-protein and protein-DNA contacts required for activation. Additional effects of regulated DNA bending in prokaryotic promoters include the amplification and translation of small physiological signals into major transcriptional responses and the control of promoter specificity for cognate regulators.
THE ANTI-SIGMA FACTORS
Authors: Hughes Kelly T. , Mathee Kalai
Published: July 2002

▪ Abstract  A mechanism for regulating gene expression at the level of transcription utilizes an antagonist of the sigma transcription factor known as the anti-sigma (anti-σ) factor. The cytoplasmic class of anti-σ factors has been well characterized. The class includes AsiA form bacteriophage T4, which inhibits Escherichia coli σ70; FlgM, present in both gram-positive and gram-negative bacteria, which inhibits the flagella sigma factor σ28; SpoIIAB, which inhibits the sporulation-specific sigma factors, σFand σG, of Bacillus subtilis; RbsW of B. subtilis, which inhibits stress response sigma factor σB; and DnaK, a general regulator of the heat shock response, which in bacteria inhibits the heat shock sigma factor σ32. In addition to this class of well-characterized cytoplasmic anti-sigma factors, a new class of homologous, inner-membrane–bound anti-σ factors has recently been discovered in a variety of eubacteria. This new class of anti-σ factors regulates the expression of so-called extracytoplasmic functions, and hence is known as the ECF subfamily of anti-sigma factors. The range of cell processes regulated by anti-σ factors is highly varied and includes bacteriophage phage growth, sporulation, stress response, flagellar biosynthesis, pigment production, ion transport, and virulence.
CELL POLARITY AND MORPHOGENESIS IN BUDDING YEAST
Authors: Madden Kevin , Snyder Michael
Published: July 2002

▪ Abstract  Eukaryotic cells respond to intracellular and extracellular cues to direct asymmetric cell growth and division. The yeast Saccharomyces cerevisiae undergoes polarized growth at several times during budding and mating and is a useful model organism for studying asymmetric growth and division. In recent years, many regulatory and cytoskeletal components important for directing and executing growth have been identified, and molecular mechanisms have been elucidated in yeast. Key signaling pathways that regulate polarization during the cell cycle and mating response have been described. Since many of the components important for polarized cell growth are conserved in other organisms, the basic mechanisms mediating polarized cell growth are likely to be universal among eukaryotes.
Functional Modulation of Escherichia Coli RNA Polymerase
Authors: Ishihama Akira
Published: July 2002

▪ Abstract  The promoter recognition specificity of Escherichia coli RNA polymerase is modulated by replacement of the σ subunit in the first step and by interaction with transcription factors in the second step. The overall differentiated state of ∼2000 molecules of the RNA polymerase in a single cell can be estimated after measurement of both the intracellular concentrations and the RNA polymerase-binding affinities for all seven species of the σ subunit and 100–150 transcription factors. The anticipated impact from this line of systematic approach is that the prediction of the expression hierarchy of ∼4000 genes on the E. coli genome can be estimated.
Assembly and Function of Type III Secretory Systems
Authors: Cornelis Guy R. , Van Gijsegem Frédérique
Published: July 2002

▪ Abstract  Type III secretion systems allow Yersinia spp., Salmonella spp., Shigella spp., Bordetella spp., and Pseudomonas aeruginosa and enteropathogenic Escherichia coli adhering at the surface of a eukaryotic cell to inject bacterial proteins across the two bacterial membranes and the eukaryotic cell membrane to destroy or subvert the target cell. These systems consist of a secretion apparatus, made of ∼25 proteins, and an array of proteins released by this apparatus. Some of these released proteins are “effectors,” which are delivered into the cytosol of the target cell, whereas the others are “translocators,” which help the effectors to cross the membrane of the eukaryotic cell. Most of the effectors act on the cytoskeleton or on intracellular-signaling cascades. A protein injected by the enteropathogenic E. coli serves as a membrane receptor for the docking of the bacterium itself at the surface of the cell. Type III secretion systems also occur in plant pathogens where they are involved both in causing disease in susceptible hosts and in eliciting the so-called hypersensitive response in resistant or nonhost plants. They consist of 15–20 Hrp proteins building a secretion apparatus and two groups of effectors: harpins and avirulence proteins. Harpins are presumably secreted in the extracellular compartment, whereas avirulence proteins are thought to be targeted into plant cells. Although a coherent picture is clearly emerging, basic questions remain to be answered. In particular, little is known about how the type III apparatus fits together to deliver proteins in animal cells. It is even more mysterious for plant cells where a thick wall has to be crossed. In spite of these haunting questions, type III secretion appears as a fascinating trans-kingdom communication device.
Microbiological Safety of Drinking Water
Authors: Szewzyk U. , Szewzyk R. , Manz W. , Schleifer K.-H.
Published: July 2002

▪ Abstract  Emerging pathogens in drinking water have become increasingly important during the decade. These include newly-recognized pathogens from fecal sources such as Cryptosporidium parvum, Campylobacter spp., and rotavirus, as well as pathogens that are able to grow in water distribution systems, like Legionella spp., mycobacteria, and aeromonads. To perform a risk analysis for the pathogens in drinking water, it is necessary to understand the ecology of these organisms. The ecology of the drinking-water distribution system has to be evaluated in detail, especially the diversity and physiological properties of water bacteria. The interactions between water bacteria and (potential) pathogens in such diverse habitats as free water and biofilms are essential for the survival or growth of hygienically relevant organisms in drinking water. Results of epidemiological studies together with ecological data are the basis for effective resource protection, water treatment, and risk assessment.
Periplasmic Stress and ECF Sigma Factors
Authors: Raivio Tracy L. , Silhavy Thomas J.
Published: July 2002

▪ Abstract  Envelope stress responses play important pysiological roles in a variety of processes, including protein folding, cell wall biosynthesis, and pathogenesis. Many of these responses are controlled by extracytoplasmic function (ECF) sigma factors that respond to external signals by means of a membrane-localized anti–sigma factor. One of the best-characterized, ECF-regulated responses is the σE envelope stress response of Escherichia coli. The σE pathway ensures proper assembly of outer-membrane proteins (OMP) by controlling expression of genes involved in OMP folding and degradation in response to envelope stresses that disrupt these processes. Prevailing evidence suggests that, in E. coli, a second envelope stress response controlled by the Cpx two-component system ensures proper pilus assembly. The sensor kinase CpxA recognizes misfolded periplasmic proteins, such as those generated during pilus assembly, and transduces this signal to the response regulator CpxR through conserved phosphotransfer reactions. Phosphorylated CpxR activates transcription of periplasmic factors necessary for pilus assembly.
MONITORING SECRETORY MEMBRANE WITH FM1-43 FLUORESCENCE
Authors: Cochilla Amanda J. , Angleson Joseph K. , Betz William J.
Published: July 2002

▪ Abstract  FM1-43 and similar styryl dyes have proven useful as probes for membrane trafficking because they reversibly stain membranes, are impermeable to membranes, and are more fluorescent when bound to membranes than when in solution. Because these dyes stain membranes in an activity-dependent manner, they are ideal for studies of neurotransmitter release mechanisms such as synaptic vesicle recycling, exocytosis, and endocytosis. FM dyes have been used in conjunction with other techniques such as fluorescent calcium indicator dyes and electrophysiological techniques to elucidate mechanisms of presynaptic calcium homeostasis and modulation of neurotransmitter release. Presynaptic membranes have been marked by FM dyes in studies of synaptogenesis and reinnervation. As a probe for endocytosed membranes, these dyes have been used to examine vacuole formation in yeast. These versatile membrane dyes are useful in a variety of applications.
Quantitative Genetics and Mouse Behavior
Authors: Wehner Jeanne M , Radcliffe Richard A , Bowers Barbara J
Published: July 2002

▪ Abstract  Quantitative differences are observed for most complex behavioral and pharmacological traits within any population. Both environmental and genetic influences regulate such individual differences. The mouse has proven to be a superb model in which to investigate the genetic basis for quantitative differences in complex behaviors. Genetically defined populations of mice, including inbred strains, heterogeneous stocks, and selected lines, have been used effectively to document these genetic differences. Recently, quantitative trait loci methods have been applied to map the chromosomal regions that regulate variation with the goal of eventually identifying the gene polymorphisms that reside in these regions.
NUTRITION SCREENING IN OLD PEOPLE: Its Place in a Coherent Practice of Preventive Health Care
Authors: Rush David
Published: July 2002

▪ Abstract  The central demographic reality of our times is the rapid aging of our society. Preventive nutritional and preventive health care of older people, therefore, are pressing issues that must be contended with. Several strategies for this are possible, including the broadcasting of general nutritional and health messages to the population, the inclusion of preventive nutrition and health as part of routine primary care, and nutrition screening: a process of self-identification by the older population in which they judge for themselves whether they are at nutritional risk and, if so, seek the care of professionals. This review focuses on some of the necessities for screening: sensitive, specific, and inexpensively applied screening devices; and explicit interventions that do not have major public health benefit for those who screen negative. Unfortunately, there is little evidence that screening is beneficial, nor have the benefits of this strategy been compared with its alternatives. Thus, the ethical imperative of screening has not been met: that because the activity is being promoted (it is not initiated by the public), its benefit must be conclusive.
Physiological and Nutritional Regulation of Enzymes of Triacylglycerol Synthesis
Authors: Coleman Rosalind A. , Lewin Tal M. , Muoio Deborah M.
Published: July 2002

Although triacylglycerol stores play the critical role in an organism's ability to withstand fuel deprivation and are strongly associated with such disorders as diabetes, obesity, and atherosclerotic heart disease, information concerning the enzymes of triacylglycerol synthesis, their regulation by hormones, nutrients, and physiological conditions, their mechanisms of action, and the roles of specific isoforms has been limited by a lack of cloned cDNAs and purified proteins. Fortunately, molecular tools for several key enzymes in the synthetic pathway are becoming available. This review summarizes recent studies of these enzymes, their regulation under varying physiological conditions, their purported roles in synthesis of triacylglycerol and related glycerolipids, the possible functions of different isoenzymes, and the evidence for specialized cellular pools of triacylglycerol and glycerolipid intermediates.
MUSCLE TRIGLYCERIDE AND INSULIN RESISTANCE
Authors: Kelley David E. , Goodpaster Bret H. , Storlien Len
Published: July 2002

▪ Abstract  Skeletal muscle contains the majority of the body's glycogen stores and a similar amount of readily accessible energy as intramyocellular triglyceride (imTG). While a number of factors have been considered to contribute to the pathogenesis of insulin resistance (IR) in obesity and type 2 diabetes mellitus (DM), this review will focus on the potential role of skeletal muscle triglyceride content. In obesity and type 2 DM, there is an increased content of lipid within and around muscle fibers. Changes in muscle in fuel partitioning of lipid, between oxidation and storage of fat calories, almost certainly contribute to accumulation of imTG and to the pathogenesis of both obesity and type 2 DM. In metabolic health, skeletal muscle physiology is characterized by the capacity to utilize either lipid or carbohydrate fuels, and to effectively transition between these fuels. We will review recent findings that indicate that in type 2 DM and obesity, skeletal muscle manifests inflexibility in the transition between lipid and carbohydrate fuels. This inflexibility in fuel selection by skeletal muscle appears to be related to the accumulation of imTG and is an important aspect of IR of skeletal muscle in obesity and type 2 DM.
PREDICTIVE VALUE OF IN VITRO MODEL SYSTEMS IN TOXICOLOGY
Authors: Davila Julio C. , Rodriguez Rosita J. , Melchert Russell B. , Acosta Daniel
Published: July 2002

▪ Abstract  The application of in vitro model systems to evaluate the toxicity of xenobiotics has significantly enhanced our understanding of drug- and chemical-induced target toxicity. From a scientific perspective, there are several reasons for the popularity of in vitro model systems. From the public perspective, in vitro model systems enjoy increasing popularity because their application may allow a reduction in the number of live animals employed in toxicity testing. In this review, we present an overview of the use of in vitro model systems to investigate target organ toxicity of drugs and chemicals, and provide selective examples of these model systems to better understand cutaneous and ocular toxicity and the role of drug metabolism in the hepatotoxicity of selected agents. We conclude by examining the value and use of in vitro model systems in industrial development of new pharmaceutical agents.
GLIAL CELLS IN NEUROTOXICITY DEVELOPMENT
Authors: Aschner M. , Allen J. W. , Kimelberg H. K. , LoPachin R. M. , Streit W. J.
Published: July 2002

▪ Abstract  Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in a layer of connective tissue. The term, or its shortened form—glia, has persisted as the preferred generic term for these cells. A reciprocal relationship exists between neurons and glia, and this association is vital for mutual differentiation, development, and functioning of these cell types. Therefore, perturbations in glial cell function, as well as glial metabolism of chemicals to active intermediates, can lead to neuronal dysfunction. The purpose of this review is to explore neuroglial sites of neurotoxicant actions, discuss potential mechanisms of glial-induced or glial-mediated central nervous system and peripheral nervous system damage, and review the role of glial cells in neurotoxicity development.
Sequencing the Entire Genomes of Free-Living Organisms: The Foundation of Pharmacology in the New Millennium
Authors: Broder Samuel , Venter J. Craig
Published: July 2002

The power and effectiveness of clinical pharmacology are about to be transformed with a speed that earlier in this decade could not have been foreseen even by the most astute visionaries. In the very near future, we will have at our disposal the reference DNA sequence for the entire human genome, estimated to contain approximately 3.5 billion bp. At the same time, the science of whole genome sequencing is fostering the computational science of bioinformatics needed to develop practical applications for pharmacology and toxicology. Indeed, it is likely that pharmacology, toxicology, bioinformatics, and genomics will merge into a new branch of medical science for studying and developing pharmaceuticals from molecule to bedside.
THE SPECTROSCOPY OF SOLVATION IN HYDROGEN-BONDED AROMATIC CLUSTERS
Authors: Zwier Timothy S.
Published: July 2002

▪ Abstract  Various aspects of molecular solvation are reviewed from the perspective provided by gas-phase aromatic solute-(solvent)nclusters. Particular emphasis is placed on hydrogen-bonded clusters, varying from 1:1 aromatic-H2O complexes up to clusters containing several water or methanol molecules. Recent advances in experimental methods for obtaining accurate structures, binding energies, and intermolecular and intramolecular vibrational spectra are highlighted. Many of these methods provide size and conformation selectivity and can be readily extended to both ground and electronically excited neutral states. The π hydrogen bond, hydrogen bonding to aromatic alcohols, water complexation to indole and its derivatives, and the hydrogen-bonded networks of benzene-(H2O)nand benzene-(CH3OH)nclusters are reviewed in special detail.
REGULATION OF OVARIAN FOLLICLE ATRESIA
Authors: Kaipia Antti , Hsueh Aaron J. W.
Published: July 2002

▪ Abstract  The majority of ovarian follicles undergo atresia, a hormonally controlled apoptotic process. Monitoring apoptotic DNA fragmentation provides a quantitative and sensitive endpoint to study the hormonal regulation of atresia in ovarian follicles. During follicle development, gonadotropins, together with local ovarian growth factors (IGF-I, EGF/TGF-α, basic FGF) and cytokine (interleukin-1β), as well as estrogens, activate different intracellular pathways to rescue follicles from apoptotic demise. In contrast, TNF-α, Fas ligand, presumably acting through receptors with a death domain, and androgens are atretogenic factors. These diverse hormonal signals probably converge on selective intracellular pathways (including genes of the bcl-2 and ICE families) to regulate apoptosis. With a constant loss of follicles from the original stockpile, the ovary provides a unique model for studying the hormonal regulation of apoptosis.
THE PULMONARY LIPOFIBROBLAST (LIPID INTERSTITIAL CELL) AND ITS CONTRIBUTIONS TO ALVEOLAR DEVELOPMENT
Authors: McGowan Stephen E. , Torday John S.
Published: July 2002

▪ Abstract  The pulmonary lipofibroblast is located in the alveolar interstitium and is recognizable by its characteristic lipid droplets. During alveolar development it participates in the synthesis of extracellular matrix structural proteins, such as collagen and elastin, and as an accessory cell to the type II pneumocyte, in the synthesis of surfactant. The lipofibroblast contains cortical contractile filaments and is thereby related to the contractile interstitial cells that are normally found at the alveolar septal tips and after lung injury. The morphologic, immunologic, and biochemical characteristics of the lipofibroblast and its probable physiologic functions are reviewed. The retinoid and lipid metabolism of the lipofibroblast is compared with that of the hepatic lipocyte and the adipocyte. Although the functions of the lipofibroblast remain incompletely characterized, this cell type is emerging as an important contributor to pulmonary alveolar septal development.
REGULATION OF GENE EXPRESSION BY HYPERTONICITY
Authors: Burg Maurice B. , Kwon Eugene D. , KÜltz Dietmar
Published: July 2002

▪ Abstract  Adaptation of cells to hypertonicity often involves changes in gene expression. Since the concentration of salt in the interstitial fluid surrounding renal inner medullary cells varies with operation of the renal concentrating mechanism and generally is very high, the adaptive mechanisms of these cells are of special interest. Renal medullary cells compensate for hypertonicity by accumulating variable amounts of compatible organic osmolytes, including sorbitol, myo-inositol, glycine betaine, and taurine. In this review we consider how these solutes help relieve the stress of hypertonicity and the nature of transporters and enzymes responsible for their variable accumulation. We emphasize recent developments concerning the molecular basis for osmotic regulation of these genes, including identification and characterization of osmotic response elements. Although osmotic stresses are much smaller in other parts of the body than in the renal medulla, similar mechanisms operate throughout, yielding important physiological and pathophysiological consequences.
THE ROLE OF TIMING IN THE BRAIN STEM AUDITORY NUCLEI OF VERTEBRATES
Authors: Oertel D.
Published: July 2002

▪ Abstract  Vertebrate animals gain biologically important information from environmental sounds. Localization of sound sources enables animals to detect and respond appropriately to danger, and it allows predators to detect and localize prey. In many species, rapidly fluctuating sounds are also the basis of communication between conspecifics. This information is not provided directly by the output of the ear but requires processing of the temporal pattern of firing in the tonotopic array of auditory nerve fibers. The auditory nerve feeds information through several parallel ascending pathways. Anatomical and electrophysiological specializations for conveying precise timing, including calyceal synaptic terminals and matching axonal conduction times, are evident in several of the major ascending auditory pathways through the ventral cochlear nucleus and its nonmammalian homologues. One pathway that is shared by all higher vertebrates makes an ongoing comparison of interaural phase for the localization of sound in the azimuth. Another pathway is specifically associated with higher frequency hearing in mammals and is thought to make use of interaural intensity differences for localizing high-frequency sounds. Balancing excitation from one ear with inhibition from the other in rapidly fluctuating signals requires that the timing of these synaptic inputs be matched and constant for widely varying sound stimuli in this pathway. The monaural nuclei of the lateral lemniscus, whose roles are not understood (although they are ubiquitous in higher vertebrates), receive input from multiple pathways that encode timing with precision, some through calyceal endings.
13C NMR of Intermediary Metabolism: Implications for Systemic Physiology
Authors: Shulman Robert G , Rothman Douglas L
Published: July 2002

▪ Abstract  The study of intermediary metabolism in biomolecules has been given new directions by recent experiments in human muscle and brain by 13C NMR. Labeled substrates, generally glucose, have enabled the fluxes to be determined in vivo, whereas the naturally abundant 13C has enabled concentrations to be measured. In muscle the glycogen synthesis pathway has been measured and the flux control determined by metabolic control analysis of data, which shows that this pathway is mainly responsible for insulin-stimulated glucose disposal and that a deficiency in the glucose transporter in the pathway is responsible for hyperglycemia in non-insulin-dependent diabetics. From a physiological point of view the most surprising result was that the heavily regulated allosteric enzyme, glycogen synthase, does not control flux but is needed to maintain homeostasis during flux changes. This novel role for a phosphorylated allosteric enzyme is proposed to be a general phenomenon in metabolic and signaling pathways, which physiologically link different cellular activities.

In human and rat brains 13C NMR measurements of the flow of labeled glucose into glutamate and glutamine simultaneously determine the rate of glucose oxidation and glutamate neurotransmitter cycling and reveal a 1:1 stoichiometry between the two fluxes. Implications for the interpretation of functional imaging studies and for psychology are discussed.

These results demonstrate how intermediary metabolism serves to connect biochemistry with systemic physiology when measured and analyzed by in vivo NMR methods.
β-Defensins in Lung Host Defense
Authors: Schutte Brian C. , McCray Paul B.
Published: July 2002

▪ Abstract  Host defenses at the mucosal surface of the airways evolved to present many layers of protection against inhaled microbes. Normally, the intrapulmonary airways are sterile. Airway secretions contain numerous factors with antimicrobial activity that contribute to innate defenses. Many protein and peptide components exert bacteriostatic or bacteriocidal effects against a wide variety of organisms and may act in synergistic or additive combinations. The β-defensins are a relatively recently described family of peptide antimicrobials that are widely expressed at mucosal surfaces, including airway and submucosal gland epithelia. These small cationic peptides are products of individual genes that exhibit broad-spectrum activity against bacteria, fungi, and some enveloped viruses. Their expression in airway epithelia may be constitutive or inducible by bacterial products or pro-inflammatory cytokines. β-defensins also act as chemokines for adaptive immune cells, including immature dendritic cells and T cells via the CCR6 receptor, and provide a link between innate and adaptive immunity. Alterations in the function of the β-defensins may contribute to disease states. Here we review much of the biology of the β-defensins, including gene discovery, genomic organization, molecular structure, regulation of expression, and function.
FASTIDIOUS XYLEM-LIMITED BACTERIAL PLANT PATHOGENS
Authors: Purcell Alexander H. , Hopkins Donald L.
Published: July 2002

▪ Abstract  Numerous bacteria have been isolated from within plants, and many reported from xylem, but only three species of xylem-limited bacteria (XLB) that are fastidious in cultural requirements, are plant pathogens, and exclusively occupy xylem, have been well characterized. Two XLB, Xylella fastidiosa and Pseudomonas syzygii, are transmitted by sucking insects that feed on xylem sap but are not transmitted mechanically from plant to plant. In contrast, Clavibacter xyli is mechanically transmitted to plants by cutting tools. All of these XLB occupy a highly specialized yet diverse ecological niche: the water-conducting systems of an extremely wide range of plant hosts. A variety of detection methods are available as diagnostic aids; each method has advantages and disadvantages; no single method is best for all uses. Molecular and genetic comparisons of strains of XLB lag behind progress being made for many other plant-pathogenic bacteria, but such studies are needed to answer important questions: (a) How do XLB move from cell to cell within plants? (b) What are the physiological and genetic bases of plant host specificity for XLB? (c) Why are only xylem-feeding specialists vectors of X. fastidiosa (and probably P. syzygii), when many leafhoppers feed regularly (but not continuously) on xylem?
ORGANIZATION OFGENESCONTROLLINGDISEASERESISTANCE IN THEPOTATOGENOME
Authors: Gebhardt Christiane , Valkonen Jari P.T.
Published: July 2002

▪ Abstract  Nineteen single dominant genes (R genes) for resistance to viruses, nematodes, and fungi have been positioned on the molecular map of potato using DNA markers. Fourteen of those genes are located in five “hotspots” for resistance in the potato genome. Quantitative trait loci (QTL) for resistance to late blight caused by the oomycete Phytophthora infestans, to tuber rot caused by the bacterium Erwinia carotovora ssp. atroseptica, and to root cyst nematodes have been identified on all 12 potato chromosomes. Some QTL for resistance to different pathogens are linked to each other and/or to resistance hotspots. Based on the genetic clustering with R genes, we propose that some QTL for resistance have a molecular basis similar to single R genes. Mapping potato genes with sequence similarity to cloned R genes of other plants and other defense-related genes reveals linkage between candidate genes, R genes, and resistance QTL. To explain the molecular basis of polygenic resistance in potato we propose (a) genes having structural similarity with cloned R genes and (b) genes involved in the defense response. The “candidate gene approach” enables the identification of markers highly useful for marker-assisted selection in potato breeding.
THE ORIGINS AND WAR PRONENESS OF INTERSTATE RIVALRIES
Authors: Vasquez John , Leskiw Christopher S.
Published: July 2002

▪ Abstract  The study of interstate rivalry, which has made major contributions to theory and research on war, is reviewed, and new research on the role of territory in the origin and war proneness of rivalries is presented. Recent research has shown that states that are rivals are much more likely to go to war than are other states, and that about half the wars fought since 1815 have involved states that are rivals. This review describes the origins of interstate rivalries in terms of whether they begin over territorial disputes, policy disputes, or disputes over the nature of a state's regime. It finds that states that dispute territory have a greater probability of becoming rivals than expected by chance, compared with states that dispute other issues. It also investigates the extent to which territorial disputes and the recurring of disputes, despite their content, are related to the onset of war.
THEPOLITICALECONOMY OFINTERNATIONALMONETARYRELATIONS
Authors: Broz J. Lawrence , Frieden Jeffry A.
Published: July 2002

▪ Abstract  The structure of international monetary relations has gained increasing prominence over the past two decades. Both national exchange rate policy and the character of the international monetary system require explanation. At the national level, the choice of exchange rate regime and the desired level of the exchange rate involve distributionally relevant tradeoffs. Interest group and partisan pressures, the structure of political institutions, and the electoral incentives of politicians therefore influence exchange rate regime and level decisions. At the international level, the character of the international monetary system depends on strategic interaction among governments, driven by their national concerns and constrained by the international environment. A global or regional fixed-rate currency regime, in particular, requires at least coordination and often explicit cooperation among national governments.
DECLARATIVE MEMORY: Insights from Cognitive Neurobiology
Authors: Eichenbaum Howard
Published: July 2002

▪ Abstract  The discovery of declarative memory as distinct from other forms of memory is a major recent acheivement in cognitive science. Basic issues about the nature of declarative memory are considered in this review from the perspective of studies on its underlying brain mechanisms. These studies have shown that declarative memory is mediated by a specific brain system including areas of the cerebral cortex and hippocampal region that make distinct functional contributions to memory processing. These processing mechanisms mediate the organization of memories in ways that can support the special properties of declarative or explicit memory expression. Furthermore, the basic properties of declarative memory in human beings can be viewed as evolving from a capacity for organized memory representation and flexible memory expression in animals.
GIFTEDNESS: An Exceptionality Examined
Authors: Robinson Ann , Clinkenbeard Pamela R.
Published: July 2002

▪ Abstract  The study of giftedness has practical origins. High-level performance intrigues people. Theoretically, the study of giftedness is related to the psychology of individual differences and has focused on the constructs of intelligence, creativity, and motivation. At a practical level, the research is largely related to school and family contexts, which develop gifts and talents in children and youth. Although broadened definitions of giftedness have emerged, the most extensive body of research available for review concentrates on intellectual giftedness. The varying definitions of giftedness and the impact of social context and diversity on the development of talent pose significant challenges for the field. Finally, the study of exceptionally advanced performance provides insight into basic psychological processes and the school contexts that develop talents in children and youth.
INFLUENCES ON INFANT SPEECH PROCESSING: Toward a New Synthesis
Authors: Werker Janet F. , Tees Richard C.
Published: July 2002

▪ Abstract  To comprehend and produce language, we must be able to recognize the sound patterns of our language and the rules for how these sounds “map on” to meaning. Human infants are born with a remarkable array of perceptual sensitivities that allow them to detect the basic properties that are common to the world's languages. During the first year of life, these sensitivities undergo modification reflecting an exquisite tuning to just that phonological information that is needed to map sound to meaning in the native language. We review this transition from language-general to language-specific perceptual sensitivity that occurs during the first year of life and consider whether the changes propel the child into word learning. To account for the broad-based initial sensitivities and subsequent reorganizations, we offer an integrated transactional framework based on the notion of a specialized perceptual- motor system that has evolved to serve human speech, but which functions in concert with other developing abilities. In so doing, we highlight the links between infant speech perception, babbling, and word learning.
The Interface of Genetics and Public Health: Research and Educational Challenges
Authors: Austin Melissa A. , Peyser Patricia A. , Khoury Muin J.
Published: July 2002

▪ Abstract  As the target date for the sequencing of the human genome approaches, there is growing recognition that public health practice, research, and education will be impacted by new genetic technologies and information and that a multidisciplinary approach is required. Research in the emerging field of public health genetics encompasses a broad range of disciplines and will increasingly involve the interactions among the investigators in these fields. An overview of these areas of research is provided, with illustrative examples. Education in public health genetics needs to address a variety of audiences, including public health graduate students and practitioners, students from related disciplines, and health care professionals. Two new graduate programs at the Universities of Michigan and Washington and training opportunities for public health professionals are described. These educational efforts must be ongoing so that the potential of genetic technology and information can be appropriately used to benefit the health of all.
APHORISMS AND CLICHÉS: The Generation and Dissipation of Conceptual Charisma
Authors: Davis Murray S.
Published: July 2002

▪ Abstract  The motivating engines of intellectual life are not true ideas but interesting ones. This article investigates the aphorism, the purest form of an interesting idea that draws the mind onward. It begins by examining the linguistic style of aphorisms, their reconceptions of experience from deceptive surfaces to more fundamental truths, their psychological and social effects on the vanity and status of their creators and conveyers, and the decline of their conceptual charisma into cliché until a surprising modification restarts the aphorism-cliché cycle. The investigation of aphorisms broadens to their intellectual and cultural contexts by examining their expansion into articles and collection into books, the different aspects of a topic revealed by aphoristic perspectives and scientific sequences, and the similarities (and differences) between aphoristic and postmodern ways of knowing. This article ends with a series of aphorisms on the cognitive substance of alluring knowledge, which distinguish some of the components of interesting ideas.
Early Traditions of African-American Sociological Thought
Authors: Young Alford A. , Deskins Donald R.
Published: July 2002

This article documents the empirical, methodological, and theoretical contributions of African-American sociologists from the late 1800s until 1945, an era that constitutes the early tradition of African-American sociological thought. African-American sociologists came to the discipline with the desire to assess the stake of African Americans in modernity, which centered on their transition to the urban sphere and the industrial socio-economic order in American society. Despite the connections between the sociological project writ-large and the quest of African-American sociologists in particular, the latter remained little regarded in the profession for years to come. While providing an overview of the contributions of African-American sociologists and the assessments made by other scholars about those contributions, this essay focuses upon the ways by which African-American sociologists have depicted the social character of black Americans. This essay also accounts for the ways that such scholars have introduced or enriched the standard paradigms and methodologies employed in American sociology, and documents the legacy that these efforts had on later sociological depictions of African Americans.
Losartan Reduces Central and Peripheral Sympathetic Nerve Activity in a Rat Model of Neurogenic Hypertension
Authors: Ye Shaohua , Zhong Huiquin , Duong Vu Ngoc , Campese Vito M.
Published: July 2002

We have developed a new model of neurogenic hypertension in the rat, in which hypertension is caused by injecting 50 μL of 10% phenol in the lower pole of one kidney. Administration of phenol in the kidney causes an immediate and persistent rise in blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity (RSNA). Because angiotensin II (Ang II) is known to stimulate central and peripheral sympathetic nervous system (SNS) activity, we have tested the hypothesis that losartan, a specific Ang II AT
1
receptor antagonist, may lower BP, at least in part, by SNS inhibition. To this end, we studied the effects of losartan on BP and SNS activity following intrarenal phenol injection. Central SNS activity was measured by NE secretion from the PH using a microdialysis technique, and peripheral SNS activity was measured by direct recording of renal nerve activity. At the end of the experiments, brains were isolated and interleukin (IL)-1β and nitric oxide synthase (NOS) mRNA gene expression was measured by RT-PCR in the PH, paraventricular nuclei (PVN), and locus ceruleus (LC). The intrarenal injection of phenol raised BP, as well as central and renal SNS activity, but reduced the abundance of IL-1β and neuronal NOS (nNOS) mRNA in the PH, PVN, and LC. Whether injected intravenously or in the lateral ventricle, losartan caused a significant (
P
<0.01) and dose-dependent inhibition of the effects of phenol on BP, NE secretion from the PH, and RSNA. Losartan also caused a significant (
P
<0.01) and dose-dependent rise in IL-1β and nNOS-mRNA gene expression in the PH, PVN, and LC of phenol-injected rats. In conclusion, these studies have shown that the intrarenal injection of phenol causes a rise in central and renal SNS activity and a decrease in IL-1β and nNOS-mRNA in the PH, PVN, and LC. Losartan prevented the rise in BP and SNS activity, as well as the decrease in IL-1β and nNOS mRNA abundance caused by phenol. These studies have demonstrated that the antihypertensive action of losartan in the phenol renal injury model is largely mediated by inhibition of central and peripheral SNS activity and suggest that activation of IL-1β and nNOS, 2 important modulators of central SNS activity, mediates the inhibitory action of losartan on SNS activity.
Mature Vascular Endothelium Can Give Rise to Smooth Muscle Cells via Endothelial-Mesenchymal Transdifferentiation
Authors: Frid Maria G. , Kale Vishakha A. , Stenmark Kurt R.
Published: July 2002

Though in the past believed to be a rare phenomenon, endothelial-mesenchymal transdifferentiation has been described with increasing frequency in recent years. It is believed to be important in embryonic vascular development, yet less is known regarding its role in the adult vasculature. Using FACS and immunomagnetic (Dynabeads) purification techniques (based on uptake of DiI-acetylated low-density lipoproteins and/or PECAM-1 expression) and double-label indirect immunostaining (for endothelial and smooth muscle [SM] markers), we demonstrate that mature bovine vascular endothelium contains cells of an endothelial phenotype (defined by VE-cadherin, von Willebrand factor, PECAM-1, and elevated uptake of acetylated low-density lipoproteins) that can undergo endothelial-mesenchymal transdifferentiation and further differentiate into SM cells (as defined by expression of α-SM-actin, SM22α, calponin, and SM-myosin). “Transitional” cells, coexpressing both endothelial markers and α-SM-actin, were consistently observed. The percentage of cells capable of endothelial-mesenchymal transdifferentiation within primary endothelial cultures was estimated as 0.01% to 0.03%. Acquisition of a SM phenotype occurred even in the absence of proliferation, in γ-irradiated (30 Gy) and/or mitomycin C–treated primary cell cultures. Initiation of transdifferentiation correlated with disruption of cell-cell contacts (marked by loss of VE-cadherin expression) within endothelial monolayers, as well as with the action of transforming growth factor-β
1
. In conclusion, our in vitro data show that mature bovine systemic and pulmonary endothelium contains cells that can acquire a SM phenotype via a transdifferentiation process that is transforming growth factor-β
1
– and cell-cell contact–dependent, but proliferation-independent.
Retinal Microvascular Abnormalities and Cognitive Impairment in Middle-Aged Persons
Authors: Wong Tien Yin , Klein Ronald , Sharrett A. Richey , Nieto F. Javier , Boland Lori L. , Couper David J. , Mosley Thomas H. , Klein Barbara E.K. , Hubbard Larry D. , Szklo Moyses
Published: July 2002

Background and Purpose

—

Cerebral microvascular disease has been hypothesized to contribute to cognitive impairment, but few clinical data are available. Here, we examine the relation of retinal microvascular abnormalities with cognitive function in middle-aged persons free of stroke.

Methods

—

The Atherosclerosis Risk in Communities Study is a population-based study with examinations every 3 years from 1987 through 1998. At visit 3, when participants were 51 to 70 years of age, retinal photographs were obtained and evaluated for retinal microvascular abnormalities according to standardized protocols. Cognitive function was assessed with standardized tests (Delayed Word Recall Test, Digit Symbol Subtest, and Word Fluency Test) at visits 2 and 4 and averaged for analysis. Persons with stroke or taking central nervous system–relevant medications were excluded, leaving 8734 with data for this study.

Results

—

After education, diabetes mellitus, blood pressure, carotid intima-media thickness, and other risk factors were controlled for, retinopathy was associated with lower cognitive test scores. The adjusted odds ratios for persons with Delayed Word Recall scores 2 SD or lower than the mean were 2.60 [95% confidence interval (CI), 1.30 to 2.91] for any retinopathy, 3.00 (95% CI, 1.81 to 4.98) for microaneurysms, 3.39 (95% CI, 1.99 to 5.78) for retinal hemorrhage, and 3.07 (95% CI, 1.53 to 6.17) for soft exudates. Results were similar for the other 2 cognitive tests and in people with and without diabetes and hypertension.

Conclusions

—

Retinopathy is independently associated with poorer cognitive function in middle-aged persons without stroke, suggesting that cerebral microvascular disease may contribute to the development of cognitive impairment.
Paraoxonase 192 Gln→Arg Polymorphism
Authors: Voetsch Barbara , Benke Kelly S. , Damasceno Benito P. , Siqueira Lúcia H. , Loscalzo Joseph
Published: July 2002

Background and Purpose

—

The etiology of arterial ischemic stroke (AIS) in the young remains unknown in one third of patients. Serum paraoxonase (PON1) is an HDL-associated esterase that hydrolyzes products of lipid peroxidation and prevents the oxidation of LDL. Two common polymorphisms in the PON1 gene, the 192 Gln (Q) → Arg (R) and 55 Leu (L) → Met (M) substitutions, determine interindividual variation in PON1 activity. The association of these polymorphisms with the risk of AIS remains controversial.

Methods

—

We analyzed 118 patients (64 women) with a first nonfatal AIS occurring <45 years of age and 118 1:1 age (±2 years)- and sex-matched controls. The PON1 polymorphisms were determined by polymerase chain reaction amplification and restriction digestion.

Results

—

The prevalence of the PON1
192RR
genotype (
P
=0.006) and the frequency of the R allele (
P
=0.010) were significantly increased among young AIS patients compared with controls. After adjustment for conventional vascular and prothrombotic risk factors, the
192RR
genotype remained independently associated with a 4-fold increase in the risk of AIS (odds ratio=4.1; 95% CI, 1.14 to 14.73). Subanalyses stratified by the presence of vascular risk factors and ethnicity did not significantly modify the effect of the PON1 192 polymorphism on AIS risk. No significant differences were found between patients and controls regarding the PON1 55 polymorphism.

Conclusions

—

These findings suggest that the PON
192RR
genotype is independently associated with an increased risk of nonfatal AIS among young adults. Further studies are necessary to understand better the mechanistic implications of these observations in the development of AIS in the young.