bluuebunny/crossref_metadata_2025 huggingface dataset:
BARRIERS TO IMPLEMENTATION OF CUMULATIVE EFFECTS ASSESSMENT
Authors: PIPER JAKE M.
Published: April 2003

Evidence is sought to identify barriers which may exist in the implementation of cumulative effects assessment (CEA). Cumulative effects may result from plans for the construction of clusters of large projects, or from gradual, piecemeal environmental change caused by numbers of individually small projects. Six CEA case studies are examined; the cases include windfarms, industrial developments, flood defence works and forestry projects. The study is based on documentary evidence plus interviews and survey involving all groups of interested stakeholders.

The study shows that barriers to CEA include lack of information and guidance, resource and skill shortages and uncertainty about where the responsibilities for such work may lie. There is a gap between the developer's legislated responsibility for information provision and the breadth of information on cumulative effects that may be useful to the competent authority. Measures to overcome these barriers are suggested, including guidance studies (by sector or type of environment) and a re-consideration of funding and responsibility. Factors motivating CEA work are also noted.
THE COMPASS INDEX OF SUSTAINABILITY: PROTOTYPE FOR A COMPREHENSIVE SUSTAINABILITY INFORMATION SYSTEM
Authors: ATKISSON ALAN , HATCHER R. LEE
Published: April 2003

Comprehensive indicators of sustainability need to be accessible, useful, and attractive to decision makers and the general public. To this end, we introduce a new aggregation, scaling, and presentation methodology. Called the "The Compass Index of Sustainability", it clusters indicators and assessment scores into four quadrants, based on the metaphor of the compass: N = Nature, E = Economy, S = Society, W = Well-being. The clusters are adapted from the theoretical work of Herman Daly ("Daly's Pyramid") as modified by Donella H. Meadows. In application, the Compass turns a complex indicator set into a series of four performance indices, one for each Compass Point, on a 0–100 scale. Normative decisions based on both scientific and social values determine the conversion formula for each indicator. The four indices can be superaggregated to produce an "Overall Sustainability Index". Once established, the scales provide clear signals about sustainability performance over time compared to an absolute or "ideal" target end-state, rather than the performance of other actors. First applied and publicly released in Orlando, Florida, USA, in July 2000, the compass proved a powerful media communications vehicle in that context, resulting in extensive regional news coverage; and it made a significant strategic impact on regional decision makers, specifically in philanthropy. Versions of the methodology are now being applied in several other US regions, cities, and communities, and other applications are being developed to assess and aggregate corporate sustainability performance as well. The authors believe the Compass Index can also be used as an interface or "add-on" to other indicator systems, such as the emerging Global Reporting Initiative; and as a management tool for comparing performance among variables, identifying priorities, and setting clear improvement targets.

This paper describes the theoretical foundations of the Compass Index; the implementation of the first prototype in Orlando, Florida; and the impact of that report on local media and decision makers. It also provides a discussion on problems and challenges associated with the model.

Note: The Compass Index of Sustainability, in format and methodology, is the intellectual property of AtKisson, Inc. All rights are reserved. Academic research is encouraged, but commercial use is restricted. Please contact the firm for licensing information.
TOWARDS A STRUCTURED APPROACH TO STRATEGIC ENVIRONMENTAL ASSESSMENT
Authors: NOBLE BRAM F. , STOREY KEITH
Published: April 2003

Considerable attention has been given to the role of strategic environmental assessment (SEA) in policy, plan and program assessment; however, there is very little consensus on an appropriate methodology for SEA. Two basic perspectives on SEA methodology emerge from the literature: first, that appropriate SEA methodologies are readily available based on the application of project-level EIA approaches to strategic assessment questions and second, that SEA requires a different, more broad-brush approach than project-level EIA. If SEA is to advance in application and effectiveness, then appropriate SEA methodologies need to be established. Despite calls for SEA to develop more independently of project-level assessment, existing SEA methodologies tend to be based on project-level EIA principles. It is argued here that while SEA can perhaps utilise many of the existing methods from project-level EIA, it requires a different, more broad-brush, but structured methodological approach. This paper reviews the current state-of-the-art of SEA methodology, and presents a generic SEA methodological framework and example based on the notion of the "best practicable environmental option".
CHOICES FOR EIA PROCESS DESIGN AND MANAGEMENT
Authors: LAWRENCE DAVID P.
Published: April 2003

The EIA process provides the framework for structuring EIA activities, events, documents and methods. An overview of examples of design and management choices available to EIA process participants is presented. The choices pertain to (1) general EIA process design and management; (2) EIA process inputs, outputs and linkages; and (3) EIA process adaptations. The available choices are more extensive than are generally recognised in EIA process characterisations. EIA process participants can select the mix of choices that best suit proposal characteristics, environmental conditions, contextual factors and their interests and priorities. An awareness of the available choices is a good first step. EIA quality and effectiveness analyses could, with appropriate adaptations and refinements, help distinguish among blends of choices that are recurrently more and less effective.
Genetics of Human Laterality Disorders: Insights from Vertebrate Model Systems
Authors: Bisgrove Brent W. , Morelli Susan H. , Yost H. Joseph
Published: April 2003

Many internal organs in the vertebrate body are asymmetrically oriented along the left-right (L-R) body axis. Organ asymmetry and some components of the molecular signaling pathways that direct L-R development are highly conserved among vertebrate species. Although individuals with full reversal of organ L-R asymmetry (situs inversus totalis) are healthy, significant morbidity and mortality is associated with perturbations in laterality that result in discordant orientation of organ systems and complex congenital heart defects. In humans and other vertebrates, genetic alterations of L-R signaling pathways can result in a wide spectrum of laterality defects. In this review we categorize laterality defects in humans, mice, and zebrafish into specific classes based on altered patterns of asymmetric gene expression, organ situs defects, and midline phenotypes. We suggest that this classification system provides a conceptual framework to help consolidate the disparate laterality phenotypes reported in humans and vertebrate model organisms, thereby refining our understanding of the genetics of L-R development. This approach helps suggest candidate genes and genetic pathways that might be perturbed in human laterality disorders and improves diagnostic criteria.
NOTCH ANDPRESENILIN: Regulated Intramembrane Proteolysis Links Development and Degeneration
Authors: Selkoe Dennis , Kopan Raphael
Published: April 2003

▪ Abstract  Intensive studies of three proteins—Presenilin, Notch, and the amyloid precursor protein (APP)—have led to the recognition of a direct intersection between early development and late-life neurodegeneration. Notch signaling mediates many different intercellular communication events that are essential for determining the fates of neural and nonneural cells during development and in the adult. The Notch receptor acts in a core pathway as a membrane-bound transcription factor that is released to the nucleus by a two-step cleavage mechanism called regulated intramembrane proteolysis (RIP). The second cleavage is effected by Presenilin, an unusual polytopic aspartyl protease that apparently cleaves Notch and numerous other single-transmembrane substrates within the lipid bilayer. Another Presenilin substrate, APP, releases the amyloid ß-protein that can accumulate over time in limbic and association cortices and help initiate Alzheimer's disease. Elucidating the detailed mechanism of Presenilin processing of membrane proteins is important for understanding diverse signal transduction pathways and potentially for treating and preventing Alzheimer's disease.
INVIVOMEASUREMENT OFFLUXES THROUGHMETABOLICPATHWAYS: The Missing Link in Functional Genomics and Pharmaceutical Research
Authors: Hellerstein Marc K.
Published: April 2003

▪ Abstract  In the postgenomic era of biology, much attention has been given to functional genomics, or the relation between genes and higher levels of organization in the cell. The latter are typically represented as mRNA, protein, or organic metabolite complements. The theme of this review is that the operational unit of function in complex biological systems is more properly seen as the fully assembled metabolic pathway in the whole organism. Due to the connectivity, interactions, and complexity of metabolic pathways, the measurement of components is an inadequate method for predicting phenotype. Measurement of the outputs of pathways (molecular fluxes) involves different tools than static measures of components, however. Here, we review recently developed stable isotope-mass spectrometric tools for measuring fluxes through metabolic pathways in vivo, focusing on the response to dietary macronutrients (carbohydrates and fats). Methods discussed include measurement of lipid dynamics, DNA replication, hepatic assembly of lipoproteins, and long-lived protein synthesis. Measuring fluxes through multiple pathways concurrently allows regulatory themes to emerge. Use of2H2O-labeling is emerging as a particularly powerful approach for multiple concurrent biosynthetic flux measurements. Several examples demonstrate that pathway flux results are often unexpected and not predicted by classic biochemistry or the expression of genes and proteins.
COMMON ENDOCRINE CONTROL OF BODY WEIGHT, REPRODUCTION, AND BONE MASS
Authors: Takeda Shu , Elefteriou Florent , Karsenty Gerard
Published: April 2003

▪ Abstract  Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, β-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.
Long-Range Resonance Energy Transfer in Molecular Systems
Authors: Scholes Gregory D.
Published: April 2003

▪ Abstract  The current state of understanding of molecular resonance energy transfer (RET) and recent developments in the field are reviewed. The development of more general theoretical approaches has uncovered some new principles underlying RET processes. This review brings many of these important new concepts together into a generalization of Förster's original theory. The conclusions of studies investigating the various approximations in Förster theory are summarized. Areas of present and future activity are discussed. The review covers Förster theory for donor-acceptor pairs and electronic coupling for singlet-singlet, triplet-triplet, and superexchange-mediated energy transfer. This includes the transition density picture of Coulombic coupling as well as electronic coupling between molecular aggregates (excitons). Spectral overlaps and ensemble energy transfer rates in disordered aggregates, the role of dielectric properties of the medium, weak versus strong coupling, and new models for energy transfer in complex molecular assemblies are also described.
Quantum Scattering Calculations on Chemical Reactions
Authors: Althorpe Stuart C. , Clary David C.
Published: April 2003

▪ Abstract  This review discusses recent quantum scattering calculations on bimolecular chemical reactions in the gas phase. This theory provides detailed and accurate predictions on the dynamics and kinetics of reactions containing three atoms. In addition, the method can now be applied to reactions involving polyatomic molecules. Results obtained with both time-independent and time-dependent quantum dynamical methods are described. The review emphasises the recent development in time-dependent wave packet theories and the applications of reduced dimensionality approaches for treating polyatomic reactions. Calculations on over 40 different reactions are described.
Organic Atmospheric Particulate Material
Authors: Seinfeld John H. , Pankow James F.
Published: April 2003

▪ Abstract  Carbonaceous compounds comprise a substantial fraction of atmospheric particulate matter (PM). Particulate organic material can be emitted directly into the atmosphere or formed in the atmosphere when the oxidation products of certain volatile organic compounds condense. Such products have lower volatilities than their parent molecules as a result of the fact that adding oxygen and/or nitrogen to organic molecules reduces volatility. Formation of secondary organic PM is often described in terms of a fractional mass yield, which relates how much PM is produced when a certain amount of a parent gaseous organic is oxidized. The theory of secondary organic PM formation is outlined, including the role of water, which is ubiquitous in the atmosphere. Available experimental studies on secondary organic PM formation and molecular products are summarized.
Optical Properties and Ultrafast Dynamics of Metallic Nanocrystals
Authors: Link Stephan , El-Sayed Mostafa A.
Published: April 2003

▪ Abstract  Noble metal particles have long fascinated scientists because of their intense color, which led to their application in stained glass windows as early as the Middle Ages. The recent resurrection of colloidal and cluster chemistry has brought about the strive for new materials that allow a bottoms-up approach of building improved and new devices with nanoparticles or artificial atoms. In this review, we discuss some of the properties of individual and some assembled metallic nanoparticles with a focus on their interaction with cw and pulsed laser light of different energies. The potential application of the plasmon resonance as sensors is discussed.
Molecular Aspects of Halide Ion Hydration: The Cluster Approach
Authors: Robertson William H. , Johnson Mark A.
Published: April 2003

▪ Abstract  This review provides a historical context for our understanding of the hydration shell surrounding halide ions and illustrates how the cluster systems can be used, in combination with theory, to elucidate the behavior of water molecules in direct contact with the anion. We discuss how vibrational predissociation spectroscopy, carried out with weakly bound argon atoms, has been employed to deduce the morphology of the small water networks attached to anions in the primary steps of hydration. We emphasize the importance of charge-transfer in the binary interaction, and discuss how this process affects the structures of the larger networks. Finally, we survey how the negatively charged water clusters (H2O)n− are providing a molecular-level perspective on how diffuse excess electrons interact with the water networks.
State-Resolved Dynamics of Photofragmentation
Authors: Lee Yuan-Pern
Published: April 2003

▪ Abstract  We discuss experiments on the dynamics of photodissociation that employ methods to select the energy, sometimes quantum states, of the reactant and to determine the quantum states and energy, sometimes also the orientation and alignment, of products. A summary of new advances of experimental methods is followed by applications to photodissociation of various types. Representative examples of simple bond fission, molecular elimination, and three-body dissociation with determined electronic states—sometimes the orientation of their angular momentum—of product atoms or distributions of electronic and internal states of product molecules illustrate the detailed information and insight that one can derive from such experiments. Photodissociation of van der Waals complexes, ions, species adsorbed on surfaces, and species in solution is excluded from this review.
Femtosecond Time-Resolved Photoelectron Spectroscopy of Polyatomic Molecules
Authors: Stolow Albert
Published: April 2003

▪ Abstract  Femtosecond time-resolved photoelectron spectroscopy is emerging as a useful technique for investigating excited state dynamics in isolated polyatomic molecules. The sensitivity of photoelectron spectroscopy to both electronic configurations and vibrational dynamics makes it well suited to the study of ultrafast nonadiabatic processes. We review the conceptual interpretation of wavepacket dynamics experiments, emphasizing the role of the final state. We discuss the advantages of the molecular ionization continuum as the final state in polyatomic wavepacket experiments and show how the electronic structure of the continuum can be used to disentangle electronic from vibrational dynamics. We illustrate these methods with examples from diatomic wavepacket dynamics, internal conversion in polyenes and polyaromatic hydrocarbons, excited state intramolecular proton transfer, and azobenzene photoiosomerization dynamics.
Conjugated Polymers as Molecular Materials: How Chain Conformation and Film Morphology Influence Energy Transfer and Interchain Interactions
Authors: Schwartz Benjamin J.
Published: April 2003

▪ Abstract  The electronic structure of conjugated polymers is of current interest because of the wide range of potential applications for such materials in optoelectronic devices. It is increasingly clear that the electronic properties of conjugated polymers depend sensitively on the physical conformation of the polymer chains and the way the chains pack together in films. This article reviews the evidence that interchain electronic species do form in conjugated polymer films, and that their number and chemical nature depend on processing conditions; the chain conformation, degree of interchain contact, and rate of energy transfer can be controlled by factors such as choice of solvent, polymer concentration, thermal annealing, presence of electrically charged side groups, and encapsulation of the polymer chains in mesoporous silica. Taken together, the results reconcile many contradictions in the literature and provide a prescription for the optimization of conjugated polymer film morphology for device applications.
Photoelectron Angular Distributions
Authors: Reid Katharine L.
Published: April 2003

▪ Abstract  Angle-resolved photoelectron spectroscopy has been performed for more than 70 years in various guises, but recently its potential to help solve in detail problems in the photoionization dynamics and intramolecular dynamics of gas-phase molecules has been recognized. One key development has been the design of experiments in appropriate geometries to extract information that pertains to the molecular frame, another has been the development of imaging spectrometers, and a third is the use of ultrafast lasers to cause photoionization. In this review, which is aimed at experimentalists, simple expressions for photoelectron angular distributions (PADs) in various experimental geometries are given and their applications explained.
Master Equation Models for Chemical Reactions of Importance in Combustion
Authors: Pilling Michael J. , Robertson Struan H.
Published: April 2003

▪ Abstract  The master equation provides a quantitative description of the interaction between collisional energy transfer and chemical reaction for dissociation, isomerization, and association processes. The approach is outlined for both irreversible and reversible dissociation, isomerization, and association reactions. There is increasing interest, especially in combustion, in association reactions that involve several linked potential wells, with the possibility of isomerization, collisional stabilization, and dissociation along several product channels. A major aim of the application of the master equation to such systems is the linking of the eigenvalues obtained by its solution to the rate coefficients for the phenomenological chemical reactions that describe the system and that are used in combustion models. The approach is illustrated by reference to the reactions C2H5 + O2, H + SO2, and the dissociation and isomerization of alkyl radicals.
Tunneling and Optical Spectroscopy of Semiconductor Nanocrystals
Authors: Banin Uri , Millo Oded
Published: April 2003

▪ Abstract  The use of a combination of tunneling and optical spectroscopy to investigate the size and shape-dependent level structure and single-electron charging phenomena in semiconductor nanocrystals is reviewed. The artificial atom character of semiconductor nanocrystal quantum dots is manifested in both the discrete level structure and in the charging multiplicity of the single-electron tunneling data, revealing s and p atomic-like states. Such states can be directly imaged using scanning tunneling microscopy, providing the extent and symmetry of the envelope wavefunctions. A detailed description of the effect of the tunneling geometry on the single-electron tunneling spectra is presented. Correlation of the optical and tunneling data allows for the assignment of the level spectrum. The generality of this powerful combination is further demonstrated in the study of quantum rods that manifest the transition from zero-dimensional quantum dots to one-dimensional quantum wires.
In Search of Perfection: Understanding the Highly Defect-Selective Chemistry of Anisotropic Etching
Authors: Hines Melissa A.
Published: April 2003

▪ Abstract  Anisotropic etchants selectively reveal a specific crystallographic plane. Although prized industrially, these etchants are poorly understood because they target specific defect sites on a surface. New methods, which rely on a combination of scanning tunneling microscopy, kinetic Monte Carlo simulations, and infrared spectroscopy, have been developed to quantify these reactions. By correlating the measured reaction rates with the structure of the defects, information about reaction mechanisms can be obtained. These techniques have also been extended to allow for the quantification of impurity reactions such as the reaction of dissolved O2, and of nonetching additives, such as alcohols. A complementary macroscopic technique, which utilizes microfabricated arrays of miscut surfaces to measure orientation-dependent kinetics, is also described.
Theory of Dipole-Bound Anions
Authors: Jordan Kenneth D. , Wang Feng
Published: April 2003

▪ Abstract  The problem of the binding of an excess electron to polar molecules and their clusters has long fascinated researchers. Although excess electrons bound to such species tend to be very extended spatially and to have little spatial overlap with the valence electrons of the neutral molecules, inclusion of electron correlation effects is essential for quantitatively describing the electron binding. The major electron correlation contribution may be viewed as a dispersion interaction between the excess electron and the electrons of the molecule or cluster. Recent work using a one-electron Drude model to describe excess electrons interacting with polar molecules is reviewed.
STM Control of Chemical Reactions: Single-Molecule Synthesis
Authors: Hla Saw-Wai , Rieder Karl-Heinz
Published: April 2003

▪ Abstract  The fascinating advances in single atom/molecule manipulation with a scanning tunneling microscope (STM) tip allow scientists to fabricate atomic-scale structures or to probe chemical and physical properties of matters at an atomic level. Owing to these advances, it has become possible for the basic chemical reaction steps, such as dissociation, diffusion, adsorption, readsorption, and bond-formation processes, to be performed by using the STM tip. Complete sequences of chemical reactions are able to induce at a single-molecule level. New molecules can be constructed from the basic molecular building blocks on a one-molecule-at-a-time basis by using a variety of STM manipulation schemes in a systematic step-by-step manner. These achievements open up entirely new opportunities in nanochemistry and nanochemical technology. In this review, various STM manipulation techniques useful in the single-molecule reaction process are reviewed, and their impact on the future of nanoscience and technology are discussed.
Structural Studies of Biomaterials Using Double-Quantum Solid-State NMR Spectroscopy
Authors: Drobny G.P. , Long J.R. , Karlsson T. , Shaw W. , Popham J. , Oyler N. , Bower P. , Stringer J. , Gregory D. , Mehta M. , Stayton P.S.
Published: April 2003

▪ Abstract  Proteins directly control the nucleation and growth of biominerals, but the details of molecular recognition at the protein-biomineral interface remain poorly understood. The elucidation of recognition mechanisms at this interface may provide design principles for advanced materials development in medical and ceramic composites technologies. Here, we describe both the theory and practice of double-quantum solid-state NMR (ssNMR) structure-determination techniques, as they are used to determine the secondary structures of surface-adsorbed peptides and proteins. In particular, we have used ssNMR dipolar techniques to provide the first high-resolution structural and dynamic characterization of a hydrated biomineralization protein, salivary statherin, adsorbed to its biologically relevant hydroxyapatite (HAP) surface. Here, we also review NMR data on peptides designed to adsorb from aqueous solutions onto highly porous hydrophobic surfaces with specific helical secondary structures. The adsorption or covalent attachment of biological macromolecules onto polymer materials to improve their biocompatibility has been pursued using a variety of approaches, but key to understanding their efficacy is the verification of the structure and dynamics of the immobilized biomolecules using double-quantum ssNMR spectroscopy.
Two-Dimensional Femtosecond Spectroscopy
Authors: Jonas David M.
Published: April 2003

▪ Abstract  The simplest two-dimensional (2D) spectra show how excitation with one (variable) frequency affects the spectrum at all other frequencies, thus revealing the molecular connections between transitions. Femtosecond 2D Fourier transform (2D FT) spectra are more flexible and share some of the remarkable properties of their conceptual parent, 2D FT nuclear magnetic resonance. When 2D FT spectra are experimentally separated into real absorptive and imaginary refractive parts, the time resolution and frequency resolution can both reach the uncertainty limit set for each resonance by the sample itself. Coherent four-level contributions to the signal provide new molecular phase information, such as relative signs of transition dipoles. The nonlinear response can be picked apart by selecting a single coherence pathway (e.g., specifying the relative signs of energy level difference frequencies during different time intervals as in the photon echo). Because molecules are frozen on the femtosecond timescale, femtosecond 2D FT experiments can separate a distribution of instantaneous molecular environments and intramolecular geometries as inhomogeneous broadening. This review provides an introduction to two-dimensional Fourier transform experiments exploiting second- and third-order vibrational and electronic nonlinearities.
CARL FREIHERR VON TUBEUF: Pioneer in Biological Control of Plant Diseases
Authors: Maloy Otis C. , Lang Klaus J.
Published: April 2003

▪ Abstract  Carl von Tubeuf, a founder of plant pathology in Europe, pioneered biological control of a major plant disease and introduced the term “biological control” to plant pathology. His book on plant diseases was one of the first to be published in English. He was proficient in many areas, and his interests included plant diseases, mycology, forest insects, white pine blister rust, the mistletoes, plant protection laws, and nature conservation.
JAMES GORDON HORSFALL: Nonconformist and Founding Father
Authors: Waggoner Paul E.
Published: April 2003

▪ Abstract  James Gordon Horsfall led the creation of the Annual Review of Phytopathology. Preeminent in the invention of organic fungicides, he also starred in epidemiology. He employed his gift with words to encourage theory and practice to march together.
SPIROPLASMA CITRI, A PLANTPATHOGENICMOLLICUTE: Relationships with Its Two Hosts, the Plant and the Leafhopper Vector
Authors: Bové Joseph M. , Renaudin Joël , Saillard Colette , Foissac Xavier , Garnier Monique
Published: April 2003

▪ Abstract  Spiroplasma citri, the type species of the genus Spiroplasma (Spiroplasmataceae, Mollicutes), is restricted to the phloem sieve tubes and transmitted by phloem sap-feeding insects, as is characteristic of the phytopathogenic mollicutes. The spiroplasmas are the only mollicutes showing motility and helical morphology, apparently mediated by a contractile fibrillar cytoskeleton bound to the inner surface of the spiroplasmal membrane. MreB genes, which are involved in cell-shape determination, have been identified in S. citri. Identified genes of other functional groups are those involved in the transmission of S. citri by the leafhoppers and genes coding for lipoproteins, including spiralin, bound to the outer surface of the spiroplasma membrane. S. citri mutants that are unable to use fructose induce only mild and delayed symptoms. Fructose utilization by the sieve tube-restricted wild-type spiroplasmas is postulated to deprive the companion cells of fructose, thereby impairing sucrose loading into the sieve tubes.
Cross-Reactive B-Cell Epitopes of Microbial and Human Heat Shock Protein 60/65 in Atherosclerosis
Authors: Perschinka Hannes , Mayr Manuel , Millonig Gunda , Mayerl Christina , van der Zee Ruurd , Morrison Sandra G. , Morrison Richard P. , Xu Qingbo , Wick Georg
Published: April 2003

Objective—Growing evidence suggests that immune reactions to heat shock protein 60 (HSP60) are involved in atherogenesis. Because of the high phylogenetic conservation between microbial and human HSP60, bacterial infections might be responsible for breaking the tolerance to self-HSP60, which is expressed on the surface of stressed arterial endothelial cells.

Methods and Results—We purified serum antibodies toEscherichia coliHSP60 (GroEL), the 60-kD chlamydial HSP, and HSP65 ofMycobacterium tuberculosisby affinity chromatography from clinically healthy subjects with sonographically proven carotid atherosclerosis. Reactivity of the purified antibodies with overlapping human HSP60 peptides was measured, and 8 shared common epitopes, recognized by all anti-bacterial HSP60/65 antibodies, were identified. Antisera specific for these cross-reactive epitopes were produced by immunizing rabbits with peptides derived from human HSP60. By immunohistochemistry, the epitopes were found to be present in the arterial wall of young subjects during the earliest stages of the disease.

Conclusions—Antibodies to microbial HSP60/65 recognize specific epitopes on human HSP60. These cross-reactive epitopes were shown to serve as autoimmune targets in incipient atherosclerosis and might provide further insights into the mechanisms of early atherogenesis.
Increased Atherosclerosis and Smooth Muscle Cell Hypertrophy in Natriuretic Peptide Receptor A

−/−

Apolipoprotein E

−/−

Mice
Authors: Alexander Matthew R. , Knowles Joshua W. , Nishikimi Toshio , Maeda Nobuyo
Published: April 2003

Objective—

Natriuretic peptide signaling is important in the regulation of blood pressure as well as in the growth of multiple cell types. To examine the role of natriuretic peptide signaling in atherosclerosis, we crossbred mice that lack natriuretic peptide receptor A (NPRA;

Npr1
−/−

) with atherosclerosis-prone mice that lack apolipoprotein E (apoE;

Apoe
−/−

).

Methods and Results—

Doubly deficient

Npr1
−/−

Apoe
−/−

mice have increased blood pressure relative to
Npr1
+/+

Apoe
−/−

mice (118±4 mm Hg compared with 108±2 mm Hg,
P
<0.05) that is coincident with a 64% greater atherosclerotic lesion size (
P
<0.005) and more advanced plaque morphology. Additionally, aortic medial thickness is increased by 52% in

Npr1
−/−

Apoe
−/−

mice relative to
Npr1
+/+

Apoe
−/−

mice (
P
<0.0001).

Npr1
−/−

Apoe
−/−

mice also have significantly greater cardiac mass (9.0±0.3 mg/g body weight) than either
Npr1
+/+

Apoe
−/−

mice (5.8±0.2 mg/g) or

Npr1
−/−

Apoe
+/+
mice (7.1±0.2 mg/g), suggesting that the lack of both NPRA and apoE synergistically enhances cardiac hypertrophy.

Conclusions—

These data provide evidence that
NPR1
is an atherosclerosis susceptibility locus and represents a potential link between atherosclerosis and cardiac hypertrophy. Our results also suggest roles for
Npr1
as well as
Apoe
in regulation of hypertrophic cell growth.
Diabetes and Progression of Carotid Atherosclerosis
Authors: Wagenknecht Lynne E. , Zaccaro Daniel , Espeland Mark A. , Karter Andrew J. , O’Leary Daniel H. , Haffner Steven M.
Published: April 2003

Objective—

We sought to determine the rate of progression of carotid atherosclerosis in persons with normal glucose tolerance, impaired glucose tolerance, and undiagnosed and diagnosed type 2 diabetes.

Methods and Results—

The Insulin Resistance Atherosclerosis Study (IRAS) is an observational cohort study in which 1192 men and women were examined at a 5-year interval. Participants of 3 ethnic groups (non-Hispanic white, African American, and Hispanic) were selected from the general population to represent a range of glucose tolerance. Baseline and follow-up ultrasound studies were obtained to estimate progression of common carotid artery (CCA) and internal carotid artery (ICA) intimal-medial thickness (IMT). Baseline glucose tolerance status was defined by an oral glucose tolerance test and World Health Organization criteria. In persons with normal glucose tolerance, progression of CCA IMT was 3.8 μm/y, and ICA IMT, 17.7 μm/y. In both CCA and ICA, progression of IMT, unadjusted for cardiovascular disease (CVD) risk factors, was approximately twice the rate in persons with diabetes than in those with normal or impaired glucose tolerance. Adjustment for CVD risk factors attenuated these differences somewhat in both sites of the carotid artery. Persons with undiagnosed diabetes had a greater ICA IMT progression rate than did persons with diagnosed diabetes (33.9 μm/y vs 26.6 μm/y,
P
=NS). Progression rates did not differ between persons with normal and impaired glucose tolerance.

Conclusions—

Progression of carotid atherosclerosis is accelerated in persons with diabetes. Progression of ICA IMT is most pronounced in persons with undiagnosed diabetes. Early identification of diabetes and CVD risk factor control might reduce its atherosclerotic complications.
Analysis of the Role of the SA Gene in Blood Pressure Regulation by Gene Targeting
Authors: Walsh Vanessa , Somody Laurence , Farrell Aldo , Zhang Beili , Brown Jane , Pritchard Catrin , Vincent Madeleine , Samani Nilesh J.
Published: April 2003

The SA gene is expressed in the proximal tubule of the kidney and may be involved in blood pressure (BP) regulation. However, direct evidence for this is lacking. We constructed and analyzed an SA-null mouse in which exons 2 and 3 of the SA gene (including the start codon) had been deleted by homologous recombination. Basal BP and BP changes in response to increased salt and to treatment with losartan were compared between mice homozygous for the targeted SA allele (
SA
−/−
mice) and littermates carrying the wild-type allele (
SA
+/+
mice). Molecular and biochemical analysis confirmed the lack of SA gene product in
SA
−/−
mice.
SA
−/−
mice grew normally, were fertile, and had no overt phenotype. With both indirect and direct techniques, basal BP was similar in
SA
−/−
and
SA
+/+
mice. A high salt diet for 4 weeks caused a significant increase in BP in
SA
−/−
and
SA
+/+
, mice but there was no difference between the 2 strains. Losartan caused a significant decrease in BP, but again the response was similar between
SA
−/−
and
SA
+/+
mice, as were their kidney renin mRNA levels. SA is not involved in the regulation of either basal or salt related BP, and the lack of differential effect in
SA
−/−
mice is not a consequence of compensatory activation of the renin-angiotensin system.
Reduced Growth Factor Responses in Vascular Smooth Muscle Cells Derived from 12/15-Lipoxygenase–Deficient Mice
Authors: Reddy Marpadga A. , Kim Young-Sook , Lanting Linda , Natarajan Rama
Published: April 2003

Biochemical and genetic evidence support the involvement of leukocyte-type 12/15-lipoxygenase enzyme and its products in the atherogenic process. We recently showed that products of the 12/15-lipoxygenase pathway play an important role in mediating hypertrophy, matrix protein production, and inflammatory gene expression in vascular smooth muscle cells (VSMC) through activation of mitogen activated protein kinases and key transcription factors. The current study is aimed at establishing the in vivo role of 12/15-lipoxygenase in VSMC by comparing growth factor–induced responses in VSMC derived from 12/15-lipoxygenase knockout mice versus genetic control wild-type mice. In the lipoxygenase knockout cells, 12/15-lipoxygenase protein was not expressed, and levels of its product, 12(S)-hydroxyeicosatetraenoic acid, were reduced (51% of wild type). Knockout cells exhibited significantly lower rates of growth factor–induced migration, fibronectin production, and incorporation of
3
H-thymidine and
3
H-leucine (54%, 55%, 61%, and 57% of wild type, respectively). Growth factor–induced superoxide production and p38 mitogen–activated protein kinase activation were also reduced in knockout cells. Serum-stimulated AP-1 transcription factor activation was markedly reduced (50% of wild type), whereas cAMP response element binding protein activation was abrogated in knockout cells. Furthermore, growth factor–induced mRNA expression of immediate early genes and fibronectin were also greatly reduced. These results suggest that the modulation of specific signaling pathways and growth-responsive genes may be responsible for the altered growth factor responses in the lipoxygenase knockout cells. They also demonstrate the important in vivo role of vascular 12/15-lipoxygenase in VSMC growth, migration, and matrix responses associated with hypertension, atherosclerosis, and restenosis.
Blood Pressure Predicts Risk of Developing End-Stage Renal Disease in Men and Women
Authors: Tozawa Masahiko , Iseki Kunitoshi , Iseki Chiho , Kinjo Kozen , Ikemiya Yoshiharu , Takishita Shuichi
Published: April 2003

Blood pressure as a risk factor for development of end-stage renal disease has not been fully studied, particularly in women. We studied the development of end-stage renal disease from 1983 through 2000 in 98 759 subjects, 46 881 men and 51 878 women, 20 to 98 years of age, who were screened in 1983 in Okinawa, Japan. Data for all dialysis patients registered from 1983 to 2000 in Okinawa were used to identify the screened subjects in whom end-stage renal disease developed. In follow-up, 400 subjects, 231 men and 169 women, had end-stage renal disease. Age, body mass index, and adjusted relative risk for systolic and diastolic blood pressure for both men and women were measured. When these results were compared with an optimal blood pressure, the relative risk of development of end-stage renal disease for those with high-normal blood pressure and hypertension were significant in both men and women. Hypertension is a significant risk factor for development of end-stage renal disease not only in men but also in women. Control of blood pressure within normal levels should be stressed as a strategy to prevent end-stage renal disease in both men and women.
Is There a Pathogenetic Role for Uric Acid in Hypertension and Cardiovascular and Renal Disease?
Authors: Johnson Richard J. , Kang Duk-Hee , Feig Daniel , Kivlighn Salah , Kanellis John , Watanabe Susumu , Tuttle Katherine R. , Rodriguez-Iturbe Bernardo , Herrera-Acosta Jaime , Mazzali Marilda
Published: April 2003

Hyperuricemia is associated with hypertension, vascular disease, renal disease, and cardiovascular events. In this report, we review the epidemiologic evidence and potential mechanisms for this association. We also summarize experimental studies that demonstrate that uric acid is not inert but may have both beneficial functions (acting as an antioxidant) as well as detrimental actions (to stimulate vascular smooth muscle cell proliferation and induce endothelial dysfunction). A recently developed experimental model of mild hyperuricemia also provides the first provocative evidence that uric acid may have a pathogenic role in the development of hypertension, vascular disease, and renal disease. Thus, it is time to reevaluate the role of uric acid as a risk factor for cardiovascular disease and hypertension and to design human studies to address this controversy.
l
-Arginine Transport in Humans With Cortisol-Induced Hypertension
Authors: Chin-Dusting Jaye P.F. , Ahlers Belinda A. , Kaye David M. , Kelly John J. , Whitworth Judith A.
Published: April 2003

A deficient
l
-arginine–nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in
l
-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period.
l
-Arginine uptake was assessed in mononuclear cells incubated with
l
-arginine (1 to 300 μmol/L), incorporating 100 nmol/L [
3
H]-
l
-arginine for a period of 5 minutes at 37°C. Forearm [
3
H]-
l
-arginine extraction was calculated after infusion of [
3
H]-
l
-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of
l
-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323±43 to 1082±245 mmol/L,
P
<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither
l
-arginine transport into mononuclear cells (placebo vs active, 26.3±3.6 vs 29.0±2.1 pmol/10 000 cells per 5 minutes, respectively, at an
l
-arginine concentration of 300 μmol/L) nor
l
-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904±434 962 vs 2 013 910±770 619 disintegrations per minute) was affected by cortisol treatment; ie, that
l
-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the
l
-arginine transport system.
Symptomatic Aortic Stenosis
Authors: Antonini-Canterin Francesco , Huang Guoqian , Cervesato Eugenio , Faggiano Pompilio , Pavan Daniela , Piazza Rita , Nicolosi Gian Luigi
Published: April 2003

Hypertension and aortic stenosis represent 2 different models of left ventricular systolic overload. Previous studies have observed different remodeling patterns in these conditions. There is, however, little information about patients with coexisting aortic stenosis and hypertension. Echocardiography was performed in 193 consecutive patients with symptomatic aortic stenosis (113 males, 80 females; mean age, 68±9 years). The prevalence of systemic hypertension was assessed. Left ventricular mass index and relative wall thickness were measured from M-mode echocardiography. Four different left ventricular remodeling patterns were identified: normal remodeling, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. A history of hypertension was present in 62 patients (32%), whereas 131 patients were normotensive. No significant differences were found between hypertensive and normotensive patients with respect to age, male/female ratio, mean New York Heart Association class, distribution of symptoms, left ventricular systolic and diastolic function, and remodeling patterns. In hypertensive patients, however, symptoms were present with larger aortic valve areas and lower stroke work loss. Systemic hypertension is not rare in patients with symptomatic aortic stenosis (32% in our series). Left ventricular remodeling patterns are quite similar in hypertensive and normotensive aortic stenosis. Our results suggest that symptoms of aortic stenosis develop with larger valve area and lower stroke work loss in hypertensive patients, probably because of the additional overload due to hypertension itself. It could suggest that in patients with coexisting hypertension and aortic stenosis, hypertension should be treated more aggressively to delay the occurrence of symptoms, and these patients should be followed-up more closely.
COX-2–Dependent Cardiac Failure in Gh/tTG Transgenic Mice
Authors: Zhang Zhibing , Vezza Roberta , Plappert Theodore , McNamara Peter , Lawson John A. , Austin Sandra , Praticò Domenico , Sutton Martin St-John , FitzGerald Garret A.
Published: April 2003

Gh is a GTP binding protein that couples to the thromboxane receptor (TP), but also functions as tissue transglutaminase II (tTG). A transgenic mouse model was generated in which Gh was overexpressed (GhOE) in ventricular myocytes under the control of the α-myosin heavy chain promoter. Heart rate was elevated and both blood pressure and left ventricular ejection fraction were depressed in GhOEs. Left ventricular mass was increased, consistent with genetic and ultrastructural evidence of hypertrophy. Fibrosis and apoptosis were also augmented. Survival declined disproportionately in older GhOEs. Cardiomyocyte expression of COX-2, thromboxane synthase (TxS), and the receptors for TxA
2
(the TP), PGF
2α
(the FP), and PGI
2
(the IP) were upregulated and urinary 8,12-
iso
-iPF
2α
-VI,2,3-dinor-6-keto-PGF
1α
and 2,3-dinor-thromboxane B
2
were increased in GhOEs, reflecting increased lipid peroxidation and cyclooxygenase (COX) activation. Selective COX-2 inhibition, TP antagonism, and suppression of lipid peroxidation each rescued the cardiac phenotype. Infusion of an FP agonist exacerbated the phenotype, whereas administration of an IP agonist improved cardiac function. Directed cardiac overexpression of Gh/tTG causes both TG activation and increased TP/Gh-dependent signaling. The COX-2–dependent increase in TxA
2
generation augments cardiac hypertrophy, whereas formation of PGI
2
by the same isozyme ameliorates the phenotype. Oxidant stress may contribute, via regulation of COX-2 expression and/or ligation of the TP and the FP by isoprostanes. Gh/tTG activation regulates expression of COX-2 and its products may differentially modulate cardiomyocyte commitment to cell death or survival.