bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship Between Productivity and Species Richness
Authors: Waide R. B. , Willig M. R. , Steiner C. F. , Mittelbach G. , Gough L. , Dodson S. I. , Juday G. P. , Parmenter R.
Published: July 2002

▪ Abstract  Recent overviews have suggested that the relationship between species richness and productivity (rate of conversion of resources to biomass per unit area per unit time) is unimodal (hump-shaped). Most agree that productivity affects species richness at large scales, but unanimity is less regarding underlying mechanisms. Recent studies have examined the possibility that variation in species richness within communities may influence productivity, leading to an exploration of the relative effect of alterations in species number per se as contrasted to the addition of productive species. Reviews of the literature concerning deserts, boreal forests, tropical forests, lakes, and wetlands lead to the conclusion that extant data are insufficient to conclusively resolve the relationship between diversity and productivity, or that patterns are variable with mechanisms equally varied and complex. A more comprehensive survey of the ecological literature uncovered approximately 200 relationships, of which 30% were unimodal, 26% were positive linear, 12% were negative linear, and 32% were not significant. Categorization of studies with respect to geographic extent, ecological extent, taxonomic hierarchy, or energetic basis of productivity similarly yielded a heterogeneous distribution of relationships. Theoretical and empirical approaches increasingly suggest scale-dependence in the relationship between species richness and productivity; consequently, synthetic understanding may be contingent on explicit considerations of scale in analytical studies of productivity and diversity.
Male-Killing, Nematode Infections, Bacteriophage Infection, and Virulence of Cytoplasmic Bacteria in the GenusWolbachia
Authors: Stevens Lori , Giordano Rosanna , Fialho Roberto F.
Published: July 2002

▪ Abstract  Wolbachia bacteria are cytoplasmic endosymbionts with a wide range of effects on their hosts and are known to infect two major invertebrate groups, arthropods and nematodes. In arthropods Wolbachia alter host reproduction, causing unidirectional and bidirectional cytoplasmic incompatibility, parthenogenesis, feminization, and embryonic male killing. Wolbachia variation in reproductive effects is indicative of a high degree of evolutionary plasticity. As many as 75% of arthropods may be infected with Wolbachia, which in addition to affecting reproduction, can also directly affect host fitness by either increasing or decreasing survival and fecundity. We review the dynamics of embryonic male-killing, including effects on insect mating behavior, as well as the distribution and implication of Wolbachia infections in filarial nematodes.

Arthropod host–Wolbachia phylogenies are not congruent, which is suggestive of horizontal transmission. The opposite has been shown in nematode-Wolbachia phylogenies, indicative of long-term association and vertical transmission. Multiple levels of parasitism within arthropods may promote horizontal transmission. Bacteriophage WO has recently been identified and is found in all Wolbachia-infected insect hosts so far examined. Extensive horizontal transmission of the phage occurs between different Wolbachia strains within a host as well as between Wolbachia in different hosts. The phage genome may carry genes important in determining both the effect of Wolbachia on arthropod host reproduction and host fitness and fecundity. The extensive horizontal transmission of the phage may explain the plasticity of Wolbachia's effect on arthropod hosts.
MITES IN FOREST CANOPIES: Filling the Size Distribution Shortfall?
Authors: Walter David Evans , Behan-Pelletier Valerie
Published: July 2002

▪ Abstract  Although often unobserved or ignored, mites usually exceed all other arthropods in abundance in forest canopies. Second in species richness only to canopy insects, the arboreal acarofauna is composed of multiple lineages of predators, scavengers, grazers, animal associates, and plant parasites that each have radiated extensively in canopy habitats. The canopy fauna is largely complementary to the mite fauna of the forest floor, suggesting that estimates of more than one million living species of mites are not extreme. Most mites are less than a millimeter in length as adults, and canopy mites tend to be smaller than species from other habitats. Even among mites, however, very small species are relatively rare, and diversity increases with decreasing size only to the penultimate size class (0.316–1 mm). This pattern may be explained by declines in microhabitat diversity or host specificity as the limit of body size in a group of organisms is approached.
HYPERPARASITISM: Multitrophic Ecology and Behavior
Authors: Sullivan Daniel J. , Völkl Wolfgang
Published: July 2002

▪ Abstract  Hyperparasitoids are secondary insect parasitoids that develop at the expense of a primary parasitoid, thereby representing a highly evolved fourth trophic level. This review evaluates multitrophic relationships and hyperparasitoid ecology. First, hyperparasitoid communities of various taxa of phytophagous and predacious insects are described. Second, specific patterns of hyperparasitoid community organization and hyperparasitoid ecology are described in detail, using the aphid-parasitoid–hyperparasitoid food web as a model system. Aphid hyperparasitoid communities consist of ecto- and endohyperparasitoids, with ectohyperparasitoids being less host specific than endohyperparasitoids. Lifetime fecundity and intrinsic rate of increase of hyperparasitoids are generally lower than those of their primary hosts. Aphid ectohyperparasitoids search randomly for hosts and do not use specific cues, whereas endohyperparasitoids gain information that originates from host plants or hosts for long-range search. Interactions with adult primary parasitoids do not influence hyperparasitoid searches, but aphid-attending ants typically prevent successful hyperparasitoid foraging. Impact of hyperparasitism on biological control is reviewed.
PREDICTINGST. LOUISENCEPHALITISVIRUSEPIDEMICS: Lessons from Recent, and Not So Recent, Outbreaks
Authors: Day Jonathan F.
Published: July 2002

▪ Abstract  St. Louis encephalitis virus was first identified as the cause of human disease in North America after a large urban epidemic in St. Louis, Missouri, during the summer of 1933. Since then, numerous outbreaks of St. Louis encephalitis have occurred throughout the continent. In south Florida, a 1990 epidemic lasted from August 1990 through January 1991 and resulted in 226 clinical cases and 11 deaths in 28 counties. This epidemic severely disrupted normal activities throughout the southern half of the state for 5 months and adversely impacted tourism in the affected region. The accurate forecasting of mosquito-borne arboviral epidemics will help minimize their impact on urban and rural population centers. Epidemic predictability would help focus control efforts and public education about epidemic risks, transmision patterns, and elements of personal protection that reduce the probability of arboviral infection. Research associated with arboviral outbreaks has provided an understanding of the strengths and weaknesses associated with epidemic prediction. The purpose of this paper is to review lessons from past arboviral epidemics and determine how these observations might aid our ability to predict and respond to future outbreaks.
The Ecology and Evolution of Ant Association in the Lycaenidae (Lepidoptera)
Authors: Pierce Naomi E. , Braby Michael F. , Heath Alan , Lohman David J. , Mathew John , Rand Douglas B. , Travassos Mark A.
Published: July 2002

▪ Abstract  The estimated 6000 species of Lycaenidae account for about one third of all Papilionoidea. The majority of lycaenids have associations with ants that can be facultative or obligate and range from mutualism to parasitism. Lycaenid larvae and pupae employ complex chemical and acoustical signals to manipulate ants. Cost/benefit analyses have demonstrated multiple trade-offs involved in myrmecophily. Both demographic and phylogenetic evidence indicate that ant association has shaped the evolution of obligately associated groups. Parasitism typically arises from mutualism with ants, and entomophagous species are disproportionately common in the Lycaenidae compared with other Lepidoptera. Obligate associations are more common in the Southern Hemisphere, in part because highly ant-associated lineages make up a larger proportion of the fauna in these regions. Further research on phylogeny and natural history, particularly of the Neotropical fauna, will be necessary to understand the role ant association has played in the evolution of the Lycaenidae.
CONTROL OF TURBULENCE
Authors: Lumley John , Blossey Peter
Published: July 2002

▪ Abstract  We discuss a few applications of active control of turbulent fluid flow and their implications for the economy and the environment. We outline a conceptual basis for control, sketching sensors, actuators, and the algorithm. The control of turbulence requires an understanding of turbulent flows beyond our present capabilities, but we describe the physical basis for control of the boundary layer: coherent structures and bursts, the connection between burst frequency and friction velocity, the change of burst frequency and drag reduction possible with polymers or active control, and other effects on burst frequency (e.g. streamline curvature, pressure gradients, and extra rates of strain). Given that the state of the flow must be sensed from the surface, and that this information is necessarily incomplete and aliased, sophisticated techniques may be required to interpret the signals. A control strategy, an algorithm, is necessary, and we express the need for a model of the flow as an interpretor and a predictor. Although surface actuators are necessary, the question of their precise effect on the fluid must be considered. We present surprising results of direct numerical simulation (DNS) of a type of actuator. Before controlling the fluid, we tried to control a model. As background, we present results of attempts to control several different models.
INTERNAL GRAVITY WAVES: From Instabilities to Turbulence
Authors: Staquet C. , Sommeria J.
Published: July 2002

▪ Abstract  We review the mechanisms of steepening and breaking for internal gravity waves in a continuous density stratification. After discussing the instability of a plane wave of arbitrary amplitude in an infinite medium at rest, we consider the steepening effects of wave reflection on a sloping boundary and propagation in a shear flow. The final process of breaking into small-scale turbulence is then presented. The influence of those processes upon the fluid medium by mean flow changes is discussed. The specific properties of wave turbulence, induced by wave-wave interactions and breaking, are illustrated by comparative studies of oceanic and atmospheric observations, as well as laboratory and numerical experiments. We then review the different attempts at a statistical description of internal gravity wave fields, whether weakly or strongly interacting.
USE OF ARABIDOPSIS FOR GENETIC DISSECTION OF PLANT DEFENSE RESPONSES
Authors: Glazebrook J. , Rogers E. E. , Ausubel F. M.
Published: July 2002

▪ Abstract  Arabidopsis thaliana (Arabidopsis) is proving to be an ideal model system for studies of host defense responses to pathogen attack. The Arabidopsis genetic system is significantly more tractable than those of other plant species, and Arabidopsis exhibits all of the major kinds of defense responses described in other plants. A large number of virulent and avirulent bacterial, fungal, and viral pathogens of Arabidopsis have been collected. In the last few years, a large number of mutations have been identified in Arabidopsis that cause a wide variety of specific defense-related phenotypes. Analysis of these mutant phenotypes is beginning to give glimpses into the complex signal transduction pathways leading to the induction of the defense responses involved in protecting plants from pathogen infection.
ALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models
Authors: Price Donald L. , Tanzi Rudolph E. , Borchelt David R. , Sisodia Sangram S.
Published: July 2002

▪ Abstract  Recent advances in a variety of areas of research, particularly in genetics and in transgenic (Tg)/gene targeting approaches, have had a substantial impact on our understanding of Alzheimer's disease (AD) and related disorders. After briefly reviewing the progress that has been made in diagnostic assessments of patients with senile dementia and in investigations of the neuropathology of AD, we discuss some of the genes/proteins that are causative or risk factors for this disease, including those encoding amyloid precursor protein, presenilin 1 and 2, and apolipoprotein E. In addition, we comment on several potential new candidate loci/genes. Subsequently, we review selected recent reports of analyses of a variety of lines of Tg mice that show several neuropathological features of AD, including Aβ-amyloid deposits and dystrophic neurites. Finally, we discuss the several important issues in future investigations of Tg mice, with particular emphasis on the influences of genetic strains on phenotype, especially behavior, and strategies for making new models of neurodegenerative disorders. We believe that investigations of these Tg models will (a) enhance understanding of the relationships between impaired performance on memory tasks and the pathological/biochemical abnormalities in brain, (b) help to clarify pathogenic mechanisms in vivo, (c) lead to identification of new therapeutic targets, and (d) allow testing of new treatment strategies first in mice and then, if successful, in humans with AD.
Hypoviruses and Chestnut Blight: Exploiting Viruses to Understand and Modulate Fungal Pathogenesis
Authors: Dawe Angus L. , Nuss Donald L.
Published: July 2002

▪ Abstract  Fungal viruses are considered unconventional because they lack an extracellular route of infection and persistently infect their hosts, often in the absence of apparent symptoms. Because mycoviruses are limited to intracellular modes of transmission, they can be considered as intrinsic fungal genetic elements. Such long-term genetic interactions, even involving apparently asymptomatic mycoviruses, are likely to have an impact on fungal ecology and evolution. One of the clearest examples supporting this view is the phenomenon of hypovirulence (virulence attenuation) observed for strains of the chestnut blight fungus, Cryphonectria parasitica, harboring members of the virus family Hypoviridae. The goal of this chapter is to document recent advances in hypovirus molecular genetics and to provide examples of how that progress is leading to the identification of virus-encoded determinants responsible for altering fungal host phenotype, insights into essential and dispensable elements of hypovirus replication, revelations concerning the role of G-protein signaling in fungal pathogenesis, and new avenues for enhancing biological control potential.
Informed Consent and Other Ethical Issues in Human Population Genetics
Authors: Greely Henry T.
Published: July 2002

▪ Abstract  Human population genetics has entered a new era of public interest, of controversy, and of ethical problems. Population genetics raises novel ethical problems because both the individuals and the populations being studied are, in effect, “subjects” of the research. Those populations are collectively subject to possible benefits and harms from the research and have interests, somewhat different from those of the individuals, that must be considered from both ethical and practical standpoints. The chapter first describes the new setting for research in human population genetics. It then examines the most controversial ethical issue in population genetics—whether researchers must obtain the informed consent of both the individual subjects and the group as a collectivity. Other vexing issues, including special problems caused by researchers' commercial interests, confidentiality, control over research uses and materials, and return of information to the population are also considered.
DNA Helicases, Genomic Instability, and Human Genetic Disease
Authors: van Brabant Anja J. , Stan Rodica , Ellis Nathan A.
Published: July 2002

DNA helicases are a highly conserved group of enzymes that unwind DNA. They function in all processes in which access to single-stranded DNA is required, including DNA replication, DNA repair and recombination, and transcription of RNA. Defects in helicases functioning in one or more of these processes can result in characteristic human genetic disorders in which genomic instability and predisposition to cancer are common features. So far, different helicase genes have been found mutated in six such disorders. Mutations in XPB and XPD can result in xeroderma pigmentosum, Cockayne syndrome, or trichothiodystrophy. Mutations in the RecQ-like genes BLM, WRN, and RECQL4 can result in Bloom syndrome, Werner syndrome, and Rothmund-Thomson syndrome, respectively. Because XPB and XPD function in both nucleotide excision repair and transcription initiation, the cellular phenotypes associated with a deficiency of each one of them include failure to repair mutagenic DNA lesions and defects in the recovery of RNA transcription after UV irradiation. The functions of the RecQ-like genes are unknown; however, a growing body of evidence points to a function in restarting DNA replication after the replication fork has become stalled. The genomic instability associated with mutations in the RecQ-like genes includes spontaneous chromosome instability and elevated mutation rates. Mouse models for nearly all of these entities have been developed, and these should help explain the widely different clinical features that are associated with helicase mutations.
Receptor Selection in B and T Lymphocytes
Authors: Nemazee David
Published: July 2002

The process of clonal selection is a central feature of the immune system, but immune specificity is also regulated by receptor selection, in which the fate of a lymphocyte’s antigen receptor is uncoupled from that of the cell itself. Whereas clonal selection controls cell death or survival in response to antigen receptor signaling, receptor selection regulates the process of V(D)J recombination, which can alter or fix antigen receptor specificity. Receptor selection is carried out in both T and B cells and can occur at different stages of lymphocyte differentiation, in which it plays a key role in allelic exclusion, positive selection, receptor editing, and the diversification of the antigen receptor repertoire. Thus, the immune system takes advantage of its control of V(D)J recombination to modify antigen receptors in such a way that self/non-self discrimination is enhanced. New information about receptor editing in T cells and B-1 B cells is also discussed.
Genomic Views of the Immune System
Authors: Staudt Louis M. , Brown Patrick O.
Published: July 2002

Genomic-scale experimentation aims to view biological processes as a whole, yet with molecular precision. Using massively parallel DNA microarray technology, the mRNA expression of tens of thousands of genes can be measured simultaneously. Mathematical distillation of this flood of gene expression data reveals a deep molecular and biological logic underlying gene expression programs during cellular differentiation and activation. Genes that encode components of the same multi-subunit protein complex are often coordinately regulated. Coordinate regulation is also observed among genes whose products function in a common differentiation program or in the same physiological response pathway. Recent application of gene expression profiling to the immune system has shown that lymphocyte differentiation and activation are accompanied by changes of hundreds of genes in parallel. The databases of gene expression emerging from these studies of normal immune responses will be used to interpret the pathological changes in gene expression that accompany autoimmunity, immune deficiencies, and cancers of immune cells.
High-Tc Superconductivity in Electron-Doped Layer Structured Nitrides
Authors: Yamanaka Shoji
Published: July 2002

▪ Abstract  A new series of superconductors based on layer structured nitrides has been developed. The general compositions of the nitrides are MNX (M = Zr, Hf; X = Cl, Br, I). The β-type polymorph consists of MN double layers sandwiched between close-packed halogen layers, which are characterized as semiconductors with a band gap of 3–4 eV. Electrons can be doped to the nitride layers by intercalation of alkali metals between the layers. Upon the intercalation, the compounds become superconductors with the transition temperatures (Tc s) as high as 13 and 25.5 K for β-ZrNCl and β-HfNCl systems, respectively. The Tc of the electron doped β-HfNCl is higher than that observed in any intermetallic compound and suggests that layered nitrides may exhibit Tc s comparable to those observed in layer structured complex copper oxide superconductors. The layer structured nitrides can be variously modified by the amounts of doping, the types of alkali metals, and the interlayer separation, which can be controlled by co-intercalation of organic molecules with alkali metals. This article dicusses topics including the synthesis and structure of the transition metal nitride halides, intercalation, superconductivity, and band structures.
FACTORS AFFECTING OUTCOME AFTER RECOVERY FROM MYOCARDIAL INFARCTION
Authors: Woo, M.D Kam S. , White, M.B Harvey D.
Published: July 2002

▪ Abstract  Patients surviving acute myocardial infarction are susceptible to heart failure, recurrence of angina, reinfarction, arrhythmias, and sudden cardiac death. Most deaths occur in the first six months after infarction. Advancing age is the most important nonmodifiable prognostic factor for long-term prognosis, whereas left ventricular function assessed clinically or measured as either ejection fraction or end-systolic volume is the most important modifiable factor. Other significant long-term prognostic factors include: postinfarction angina at rest, inducible ischemia during exercise testing with or without radioisotope imaging, severity and extent of coronary artery disease, patency of the infarct-related artery, late ventricular arrhythmias, decreased heart rate variability, cigarette smoking, hypercholesterolemia, and diabetes mellitus. Identification of these adverse prognostic factors permits risk stratification and enables physicians to determine the most appropriate and cost-effective treatment.

Most patients should have a stress test for inducible ischemia and a noninvasive (echo or radionuclide) assessment of left ventricular function. For high-risk patients such as those with prior infarction, heart failure, early postinfarction angina, or frequent late ventricular arrhythmias, coronary angiography and ventriculography prior to discharge are recommended. Assessment of late potentials and heart rate variability will help identify a subgroup of patients at risk for ventricular arrhythmias and cardiac death. However, a more accurate prediction of reinfarction is not possible at present, and no reliable test for atherosclerotic plaque instability has been developed.
GENE TRANSFER TO HEMATOPOIETIC STEM CELLS: Implications for Gene Therapy of Human Disease
Authors: Dunbar, M.D Cynthia E.
Published: July 2002

▪ Abstract  Transfer of new genetic material to hematopoietic stem cells and expression of the gene product in daughter cells of various lineages is an exciting approach to the treatment of congenital and acquired human diseases. This review summarizes the current status of retroviral and adeno-associated viral vectors for gene transfer to human hematopoietic cells, including extensive preclinical data as well as preliminary results from ongoing clinical trials.
BARTONELLA (ROCHALIMAEA) INFECTIONS: Beyond Cat Scratch
Authors: Schwartzman, M.D W.
Published: July 2002

▪ Abstract  Five species of Bartonella have been found to infect humans, henselae, quintana, elizabethae, bacilliformis, and vinsonii. The most common of these in North America are Bartonella quintana and Bartonella henselae, the agents of trench fever, bacillary angiomatosis, and parenchymal peliosis, and in the case of B. henselae cat-scratch disease. B. bacilliformisis endemic in Peru and Ecuador, where it causes oroya fever or Carrion's disease. New methods of diagnosing Bartonella infections have resulted in increased recognition of the many manifestations of these infections. Early recognition is crucial, as these are potentially fatal opportunistic infections that usually respond rapidly to appropriate antimicrobial therapy.
VON WILLEBRAND'S DISEASE
Authors: Ewenstein, MD, PhD Bruce M.
Published: July 2002

▪ Abstract  von Willebrand's disease (vWD) arises from abnormalities in von Willebrand factor (vWF), an adhesive glycoprotein uniquely involved in key aspects of both primary and secondary hemostasis. The current classification distinguishes disorders arising from partial (type 1) or complete (type 3) deficiencies and from qualitative defects (type 2). Type 2 vWD is further divided into four subtypes (A, B, N, and M), reflecting distinct classes of functional abnormalities. Missense mutations account for most of type 2 vWD, whereas major disruptions in the vWF gene produce type 3 variants. The molecular basis of type 1 vWD is largely undefined. The laboratory diagnosis of vWD and its several variants is made on the basis of immunologic and functional studies of vWF, factor VIII levels, and specialized electrophoretic analyses (multimer gels). The mainstay of therapy for most patients with vWD is desmopressin, a pharmacologic agent that stimulates the release of endogenous pools of vWF. Cryoprecipitate and selected factor VIII concentrates are useful sources of exogenous vWF for the treatment of patients unresponsive to this desmopressin.
Current Concepts in Cobalamin Deficiency
Authors: Carmel Ralph
Published: July 2002

The application of sensitive metabolic tests, such as the deoxyuridine suppression test and measurement of homocysteine and methylmalonic acid, to cobalamin status has identified the entity of mild, preclinical cobalamin deficiency. This state, common in the elderly, responds to cobalamin therapy. Preclinical deficiency may exist within the nervous system as well, although this requires further study. Nevertheless, it is well to remember that not all low cobalamin levels and not all abnormal metabolite results reflect cobalamin deficiency. Interpretation of metabolic results still requires caution, as do proposals to raise the cut-off point for low cobalamin levels to capture some normal levels that are associated with metabolic abnormality. The recognition of mild, preclinical deficiency has opened up many important issues. These include identifying its causes, what should be done about it, and what the clinical impact of the hyperhomocysteinemia itself is. Although malabsorptive disorders, especially food-cobalamin malabsorption, underlie about half of all cases of preclinical deficiency, no cause can be found in the remainder of these cases; poor dietary intake appears to be uncommon. In addition, unusual states of neurologically symptomatic cobalamin deficiency are being recognized, such as nitrous oxide exposure in patients with unrecognized deficiency and severe deficiency in children of mildly deficient mothers. All of these have broadened and complicated the picture of cobalamin deficiency while providing greater opportunities for prevention.
Genetic Testing for Cancer Predisposition
Authors: Eng Charis , Hampel Heather , Chapelle Albert de la
Published: July 2002

▪ Abstract  Clinical cancer genetics is becoming an integral part of the care of cancer patients. This review describes the clinical aspects, genetics, and clinical genetic management of most of the major hereditary cancer susceptibility syndromes. Multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and familial adenomatous polyposis are examples of syndromes for which genetic testing to identify at-risk family members is considered the standard of care. Genetic testing for these syndromes is sensitive and affordable, and it will change medical management. Cancer genetic counseling and testing is probably beneficial in other syndromes, such as the hereditary breast cancer syndromes, hereditary nonpolyposis colorectal cancer syndrome, Peutz-Jeghers syndrome, and juvenile polyposis. There are also hereditary cancer syndromes for which testing is not yet available and/or is unlikely to change medical management, including Li-Fraumeni syndrome and hereditary malignant melanoma. Thorough medical care requires the identification of families likely to have a hereditary cancer susceptibility syndrome for referral to cancer genetics professionals.
Surgical Management of Heart Failure: An Overview
Authors: Zeltsman David , Acker Michael A.
Published: July 2002

▪ Abstract  Cardiac transplantation remains the gold standard of surgical therapies for advanced and end-stage heart failure. However, this very limited option trades one disease for another and can benefit only a small minority of patients. Heart failure is currently considered secondary to a structural increase in ventricular chamber volume or remodeling. Surgical therapies formerly contraindicated for the failing heart, as well as new therapies, can successfully affect ventricular remodeling and improve cardiac function. Surgical revascularization for patients with ejection fractions <20% is becoming common. Mitral valve repair is being explored, with surprisingly low operative mortality and encouraging intermediate results. Direct surgical approaches to restoring normal geometry and size to failing hearts, such as left ventricular reduction (Batista procedure), endoventricular patch plasty (Dor procedure), cardiomyoplasty, and prosthetic external constraints are under clinical investigation. Developments in mechanical assist therapy and a new generation of implantable intracorporeal assist devices are also discussed.
GENETICS OF EUBACTERIAL CAROTENOID BIOSYNTHESIS: A Colorful Tale
Authors: Armstrong Gregory A.
Published: July 2002

▪ Abstract  Carotenoids represent one of the most widely distributed and structurally diverse classes of natural pigments, with important functions in photosynthesis, nutrition, and protection against photooxidative damage. In the eubacterial community, yellow, orange, and red carotenoids are produced by anoxygenic photosynthetic bacteria, cyanobacteria, and certain species of nonphotosynthetic bacteria. Many eukaryotes, including all algae and plants, as well as some fungi, also synthesize these pigments. In noncarotenogenic organisms, such as mammals, birds, amphibians, fish, crustaceans, and insects, dietary carotenoids and their metabolites also serve important biological roles. Within the last decade, major advances have been made in the elucidation of the molecular genetics, the biochemistry, and the regulation of eubacterial carotenoid biosynthesis. These developments have important implications for eukaryotes, and they make increasingly attractive the genetic manipulation of carotenoid content for biotechnological purposes.
THE ROLE OF VESICULAR TRANSPORT PROTEINS IN SYNAPTIC TRANSMISSION AND NEURAL DEGENERATION
Authors: Liu Yongjian , Edwards Robert H.
Published: July 2002

▪ Abstract  Classical neurotransmitters are synthesized in the cytoplasm, so they require transport into secretory vesicles for regulated exocytotic release. Previous work has identified distinct vesicular transport activities for the different classical transmitters, and all depend on the H+-electrochemical gradient across the vesicle membrane but differ in the extent to which they rely on the chemical and electrical components of this gradient. Drugs that interfere with vesicular amine transport have implicated this activity in psychiatric disease. Selection for a cDNA encoding vesicular amine transport in the neurotoxin MPP+ also implicates the activity in Parkinson's disease. Molecular cloning of vesicular monoamine transporters shows sequence similarity to bacterial antibiotic resistance proteins, supporting a role for transport in detoxification and defining a novel mammalian gene family that now also includes a transporter for acetylcholine. Current work focuses on the mechanism of transport and the role that regulation of activity and its subcellular localization have in transmitter release, behavior, and neural degeneration.
Control of Cell Divisions in the Nervous System: Symmetry and Asymmetry
Authors: Lu Bingwei , Jan Lily , Jan Yuh-Nung
Published: July 2002

The diverse cell types in the nervous system are derived from neural progenitor cells. Neural progenitors can undergo symmetric divisions to expand cell population or asymmetric divisions to generate diverse cell types. Furthermore, neural progenitors must exit the cell cycle in a developmentally regulated manner to allow for terminal differentiation. The patterns of neural progenitor divisions have been characterized in vertebrates and invertebrates. During the course of nervous system development, extrinsic and intrinsic cues dictate the division patterns of neural progenitors by influencing their cell cycle behavior and cellular polarity. The identification in Drosophila of asymmetrically distributed fate determinants, adapter molecules, and polarity organizing molecules that participate in asymmetric neural progenitor divisions should provide points of entry for studying similar asymmetric divisions in vertebrates.
PARITY-VIOLATING ELECTRON SCATTERING AND NUCLEON STRUCTURE
Authors: Beck D. H. , McKeown R. D.
Published: July 2002

▪ Abstract  The measurement of parity violation in the helicity dependence of electron-nucleon scattering provides unique information about the basic quark structure of the nucleons. This review presents the general formalism of parity-violating electron scattering, with emphasis on elastic electron-nucleon scattering. The physics issues addressed by such experiments are discussed, and the major goals of the presently envisioned experimental program are identified. Results from a recent series of experiments are summarized and the future prospects of this program are discussed.
ROLE OF NUTRITION IN PREVENTION OF THE PROGRESSION OF RENAL DISEASE
Authors: Maroni Bradley J. , Mitch William E.
Published: July 2002

▪ Abstract  In rats with renal disease, low-protein diets slow the decline in renal function, histologic damage, and mortality. Low-protein (and phosphorus) diets can also ameliorate uremic symptoms, secondary hyperparathyroidism, and metabolic acidosis in patients with chronic renal failure. Albeit controversial, evidence also suggests that dietary protein restriction can slow the rate of progression of renal failure and the time until end-stage renal failure. These dietary regimens appear to be safe and patients with chronic renal failure are able to activate normal compensatory mechanisms designed to conserve lean body mass when dietary protein intake is restricted. When low-protein diets are prescribed, patients should be closely monitored to assess dietary compliance and to ensure nutritional adequacy. Evidence that the spontaneous intake of dietary protein decreases in patients with progressive chronic renal failure who consume unrestricted diets should not be construed as an argument against the use of low-protein diets. Rather, it is a persuasive argument to restrict dietary protein intake in order to minimize complications of renal failure while preserving nutritional status.
MECHANISMS OF ACTION OF BISPHOSPHONATES
Authors: Rodan Gideon A.
Published: July 2002

▪ Abstract  Bisphosphonates (BPs) are pyrophosphate analogs in which the oxygen bridge has been replaced by carbon and diverse carbon side chains have generated a large family of compounds. Several are potent inhibitors of bone destruction (resorption) and are in clinical use for the treatment and prevention of osteoporosis, Paget's disease, hypercalcemia caused by malignancy, tumor metastases in bone, and other bone ailments. Selective action on bone is based on the binding of the BP moiety to the bone mineral. The molecular mode of action of BPs, which may differ from compound to compound, is unknown. However, at the tissue level, all BPs inhibit bone destruction and lead to an increase in bone mineral density by decreasing bone resorption and bone turnover. At the cellular level, the ultimate target of BP action is the osteoclast, the bone resorbing cell. In vitro evidence shows BP inhibition of osteoclast formation, via action on osteoblasts, and there is in vitro and in vivo evidence for BP inhibition of osteoclast activity. There is in vivo and in vitro evidence for increased apoptosis. The relative contribution of these various effects on the therapeutic action of BPs remains to be established. At the molecular level, it is not known if BPs act on a single or multiple targets. Enzymes in the cholesterol biosynthesis pathway and protein tyrosine phosphatases were shown to be inhibited by BPs.
GROWTH HORMONE AS THERAPY FOR OLDER MEN AND WOMEN
Authors: Marcus Robert , Hoffman Andrew R.
Published: July 2002

▪ Abstract  Progressive deficits in the growth hormone (GH)/insulin-like growth factor I axis may contribute to the acquired biochemical, body composition, and functional changes of normal human aging, but they do not offer a sole, or even a major explanation for these changes. The concept that GH “replacement” would materially benefit the daily function of older men and women finds little support in the results of the controlled clinical trials that have been reported. GH, either as monotherapy or in combination with antiresorptive medication, does not offer a clinically useful improvement in bone mass, and it is difficult to find a rationale for its use in the treatment of osteoporosis. GH may yet prove to be a useful agent for older men and women in the management of other clinical syndromes, such as visceral obesity, but conclusions in this area await compelling evidence. For the time being, potential benefits of GH in older men and women must be viewed with skepticism, and use of this agent outside the context of a clinical trial is not justified.
Antisense Oligonucleotides: Promise and Reality
Authors: Lebedeva Irina , Stein CA
Published: July 2002

Antisense oligonucleotides have been used for more than a decade to downregulate gene expression. Phosphodiester oligonucleotides are nuclease sensitive, and the more nuclease-resistant phosphorothioate oligonucleotides are now in common use in the laboratory and have entered clinical trials. However, these molecules are highly bioactive and may inhibit gene expression by more than one mechanism. Although some dramatic successes have been demonstrated, it can still be difficult to properly interpret experimental data derived from the use of this class of oligonucleotide. This review discusses some of these issues with particular reference to a major area of current interest—inhibition of bcl-2 expression in tumor cells.
Dimerization: An Emerging Concept for G Protein–Coupled Receptor Ontogeny and Function
Authors: Angers Stephane , Salahpour Ali , Bouvier Michel
Published: July 2002

In the last four to five years, the view that G protein–coupled receptors (GPCRs) function as monomeric proteins has been challenged by numerous studies, which suggests that GPCRs exist as dimers or even higher-structure oligomers. Recently, biophysical methods based on luminescence and fluorescence energy transfer have confirmed the existence of such oligomeric complexes in living cells. Although no consensus exists on the role of receptor dimerization, converging evidence suggests potential roles in various aspects of receptor biogenesis and function. In several cases, receptors appear to fold as constitutive dimers early after biosynthesis, whereas ligand-promoted dimerization at the cell surface has been proposed for others. The reports of heterodimerization between receptor subtypes suggest a potential level of receptor complexity that could account for previously unexpected pharmacological diversities. In addition to fundamentally changing our views on the structure and activation processes of GPCRs, the concept of homo- and heterodimerization could have dramatic impacts on drug development and screening.
DENSITYFUNCTIONALTHEORY OFBIOLOGICALLYRELEVANTMETALCENTERS
Authors: Siegbahn Per E. M. , Blomberg Margareta R. A.
Published: July 2002

▪ Abstract  Recent applications of density functional theory to biologically relevant metal centers are reviewed. The emphasis is on reaction mechanisms, structures, and modeling. The accuracy of different functionals is discussed for standard benchmark tests of first- and second-row molecules and for transition metal systems. Modeling aspects of the protein metal complexes are discussed regarding both the size of the model being treated quantum mechanically and the treatment of the protein surrounding it. To illustrate the effects, structures computed without the effects of the protein are compared with experimental structures from enzymes, and results from simple dielectric models of the protein for electron transfer processes are described. The choice of spin state is discussed for multimetal complexes. Examples of mechanisms studied recently by density functional theory are described, such as O2and methane activation in methane monooxygenase and O2formation in photosystem II.
Peptides and Proteins in the Vapor Phase
Authors: Jarrold Martin F.
Published: July 2002

This article provides a review of recent studies of the properties of unsolvated (and partially solvated) peptides and proteins. The methods used to produce vapor-phase peptide and protein ions are described along with some of the techniques used to study them, such as H/D exchange, blackbody infrared radiative dissociation, and ion mobility measurements. Studies of unsolvated peptides and proteins provide information about their intrinsic intramolecular interactions. The topics covered include the role of zwitterions and salt bridges in the vapor phase, Coulomb interactions in multiply charged ions, the unfolding and refolding of vapor-phase proteins, and the stability of unsolvated helices and sheets. Finally, dehydration and rehydration studies of proteins in the vapor phase are described. These can provide exquisitely detailed information about hydration interactions, such as the enthalpy and entropy changes associated with adsorbing individual water molecules.
Transient Laser Frequency Modulation Spectroscopy
Authors: Hall Gregory E. , North Simon W.
Published: July 2002

Explicitly time-dependent implementations of optical frequency modulation spectroscopy have been recently applied to a wide range of problems in chemical physics. We provide a brief description of the methodology, with an emphasis on its intrinsic advantages for interrogating transient species. Several examples highlight the application of the technique to high-resolution absorption spectra of free radicals, rate measurements for gas-phase reactions, and Doppler spectroscopy of the gas-phase products of photoinitiated reactions.
Basic Mechanisms of Atrial Fibrillation—Very New Insights into Very Old Ideas
Authors: Nattel S. , Li D. , Yue L.
Published: July 2002

▪ Abstract  Atrial fibrillation (AF) was recognized and studied extensively in the early twentieth century, but many fundamental aspects of the arrhythmia were poorly understood until quite recently. It is now recognized that AF can be initiated by a variety of mechanisms that share the ability to cause extremely rapid, irregular atrial electrical activity. Once initiated, AF causes alterations in atrial electrical properties (electrical remodeling), including both rapid functional changes and slower alterations in ion channel gene expression, which promote the maintenance of AF and facilitate reinitiation of the arrhythmia should it terminate. Electrical remodeling decreases the atrial refractory period in a heterogeneous way, thus decreasing the size and stability of potential functional atrial reentry waves and promoting multiple-circuit reentry. Whatever the initial cause of AF, electrical remodeling is likely to be a final common pathway that ultimately supervenes. Recent advances in understanding ion channel function, regulation, and remodeling at the molecular level have allowed for a much more detailed appreciation of the basic determinants of AF. Improvements in the clinical management of AF will inevitably follow the recent advances in our understanding of its detailed pathophysiology.
BREEDING DISEASE-RESISTANT WHEATS FOR TROPICAL HIGHLANDS AND LOWLANDS
Authors: Dubin H.J. , Rajaram S.
Published: July 2002

▪ Abstract  Wheat is grown on about 10 million ha in the tropical highlands and lowlands of the world, where it is an important food source. Many farmers in these areas work under subsistence conditions. Wheat diseases in tropical regions can be severe and require significant efforts to control. For economic and environmental reasons, host plant resistance is the most appropriate and sustainable disease control method. We describe highland and lowland tropical wheat regions and discuss CIMMYT's breeding strategies, philosophies, and progress in developing resistance to the major diseases such as rusts, foliar blights, fusarium scab, BYD, and spot blotch. Additionally, we review the role of national wheat research programs and beneficial spillovers of our combined breeding efforts to other wheat production areas of the world.
ORGANIZATIONAL DIVERSIFICATION IN THE AMERICAN HOSPITAL
Authors: Snail Timothy S. , Robinson James C.
Published: July 2002

▪ Abstract  This paper outlines a conceptual framework of organizational diversification and assesses the state of empirical research on hospital organizational change. The literature on economic organization of hospitals, one of the most developed branches of health services research, still has only weak ties to economic theory. Evolving physician-hospital organizations do not fit into existing frameworks based on horizontal integration, vertical integration, or diversification. Empirical research has primarily focused on horizontal integration, and cause-effect relationships are often obscured by models that depart from economic theory and lack controls for self-selection bias. Recent empirical studies indicate that hospital mergers had moderate, rather than dramatic, effects on the rate of change in operating costs, staffing, and scale. Mergers rarely resulted in hospital closure, but were as likely to result in acute care consolidation and restructuring as in conversion to non-acute inpatient uses. While administrative costs were higher in for-profit than non-profit system hospitals, total costs were similar. System hospitals had lower marginal and average costs per stay than independent hospitals. Hospital vertical integration into subacute care was largely an artifact of the governmental uniform pricing system, which encouraged vertical integration. Hospitals that shared governance or financial risks with physicians outperformed those with high levels of physician governance and financial integration (e.g. stock ownership). Formal physician-hospital organizational arrangements often served to coordinate managed care contracting or to forge links with primary care group practices. Hospital diversification into related services improved short-term financial performance over unrelated diversification, although long-term performance was similar.