bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational Regulation and RNA Localization in Drosophila Oocytes and Embryos
Authors: Johnstone Oona , Lasko Paul
Published: July 2002

▪ Abstract  Translational control is a prevalent means of gene regulation during Drosophila oogenesis and embryogenesis. Multiple maternal mRNAs are localized within the oocyte, and this localization is often coupled to their translational regulation. Subsequently, translational control allows maternally deposited mRNAs to direct the early stages of embryonic development. In this review we outline some general mechanisms of translational regulation and mRNA localization that have been uncovered in various model systems. Then we focus on the posttranscriptional regulation of four maternal transcripts in Drosophila that are localized during oogenesis and are critical for embryonic patterning: bicoid (bcd), nanos (nos), oskar (osk), and gurken (grk). Cis- and trans-acting factors required for the localization and translational control of these mRNAs are discussed along with potential mechanisms for their regulation.
The Biology of Chemokines and their Receptors
Authors: Rossi Devora , Zlotnik Albert
Published: July 2002

During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors. The chemokine field has also received considerable attention since chemokine receptors were found to act as co-receptors for HIV infection ( 1 ). In addition, chemokines, along with adhesion molecules, are crucial during inflammatory responses for a timely recruitment of specific leukocyte subpopulations to sites of tissue damage. However, chemokines and their receptors are also important in dendritic cell maturation ( 2 ), B ( 3 ), and T ( 4 ) cell development, Th1 and Th2 responses, infections, angiogenesis, and tumor growth as well as metastasis ( 5 ). Furthermore, an increase in the number of chemokine/receptor transgenic and knock-out mice has helped to define the functions of chemokines in vivo. In this review we discuss some of the chemokines’ biological effects in vivo and in vitro, described in the last few years, and the implications of these findings when considering chemokine receptors as therapeutic targets.
Reservoirs for HIV-1: Mechanisms for Viral Persistence in the Presence of Antiviral Immune Responses and Antiretroviral Therapy
Authors: Pierson Theodore , McArthur Justin , Siliciano Robert F.
Published: July 2002

The success of combination antiretroviral therapy for HIV-1 infection has generated interest in mechanisms by which the virus can persist in the body despite the presence of drugs that effectively inhibit key steps in the virus life cycle. It is becoming clear that viral reservoirs established early in the infection not only prevent sterilizing immunity but also represent a major obstacle to curing the infection with the potent antiretroviral drugs currently in use. Mechanisms of viral persistence are best considered in the context of the dynamics of viral replication in vivo. Virus production in infected individuals is largely the result of a dynamic process involving continuous rounds of de novo infection of and replication in activated CD4+T cells with rapid turnover of both free virus and virus-producing cells. This process is largely, but not completely, interrupted by effective antiretroviral therapy. After a few months of therapy, plasma virus levels become undetectable in many patients. Analysis of viral decay rates initially suggested that eradication of the infection might be possible. However, there are several potential cellular and anatomical reservoirs for HIV-1 that may contribute to long-term persistence of HIV-1. These include infected cell in the central nervous system and the male urogenital tract. However, the most worrisome reservoir consists of latently infected resting memory CD4+T cells carrying integrated HIV-1 DNA. Definitive demonstration of the presence of this form of latency required development of methods for isolating extremely pure populations of resting CD4+T cells and for demonstrating that a small fraction of these cells contain integrated HIV-1 DNA that is competent for replication if the cells undergo antigen-driven activation. Most of the latent virus in resting CD4+T cells is found in cells of the memory phenotype. The half-life of this latent reservoir is extremely long (44 months). At this rate, eradication of this reservoir would require over 60 years of treatment. Thus, latently infected resting CD4+T cells provide a mechanism for life-long persistence of replication-competent forms of HIV-1, rendering unrealistic hopes of virus eradication with current antiretroviral regimens. The extraordinary stability of the reservoir may reflect gradual reseeding by a very low level of ongoing viral replication and/or mechanisms that contribute to the intrinsic stability of the memory T cell compartment. Given the substantial long-term toxicities of current combination therapy regimens, novel approaches to eradicating this latent reservoir are urgently needed.
GP120: Biologic Aspects of Structural Features
Authors: Poignard Pascal , Saphire Erica Ollmann , Parren Paul WHI , Burton Dennis R.
Published: July 2002

▪ Abstract  HIV-1 particles are decorated with a network of densely arranged envelope spikes on their surface. Each spike is formed of a trimer of heterodimers of the gp120 surface and the gp41 transmembrane glycoproteins. These molecules mediate HIV-1 entry into target cells, initiating the HIV-1 replication cycle. They are a target for entry-blocking drugs and for neutralizing Abs that could contribute to vaccine protection. The crystal structure of the core of gp120 has been recently solved. It reveals the structure of the conserved HIV-1 receptor binding sites and some of the mechanisms evolved by HIV-1 to escape Ab responses. The gp120 consists of three faces. One is largely inaccessible on the native trimer, and two faces are exposed but apparently have low immunogenicity, particularly on primary viruses. We have modeled HIV-1 neutralization by a CD4 binding site monoclonal Ab, and we propose that neutralization takes place by inhibition of the interaction between gp120 and the target cell membrane receptors as a result of steric hindrance. Knowledge of gp120 structure and function should assist in the design of new drugs as well as of an effective vaccine. In the latter case, circumventing the low immunogenicity of the HIV-1 envelope spike is a major challenge.
B Cell Development Pathways
Authors: Hardy Richard R. , Hayakawa Kyoko
Published: July 2002

B cell development is a highly regulated process whereby functional peripheral subsets are produced from hematopoietic stem cells, in the fetal liver before birth and in the bone marrow afterward. Here we review progress in understanding some aspects of this process in the mouse bone marrow, focusing on delineation of the earliest stages of commitment, on pre-B cell receptor selection, and B cell tolerance during the immature-to-mature B cell transition. Then we note some of the distinctions in hematopoiesis and pre-B selection between fetal liver and adult bone marrow, drawing a connection from fetal development to B-1/CD5+B cells. Finally, focusing on CD5+cells, we consider the forces that influence the generation and maintenance of this distinctive peripheral B cell population, enriched for natural autoreactive specificities that are encoded by particular germline VH-VLcombinations.
Lymphocyte-Mediated Cytotoxicity
Authors: Russell John H. , Ley Timothy J.
Published: July 2002

Virtually all of the measurable cell-mediated cytotoxicity delivered by cytotoxic T lymphocytes and natural killer cells comes from either the granule exocytosis pathway or the Fas pathway. The granule exocytosis pathway utilizes perforin to traffic the granzymes to appropriate locations in target cells, where they cleave critical substrates that initiate DNA fragmentation and apoptosis; granzymes A and B induce death via alternate, nonoverlapping pathways. The Fas/FasL system is responsible for activation-induced cell death but also plays an important role in lymphocyte-mediated killing under certain circumstances. The interplay between these two cytotoxic systems provides opportunities for therapeutic interventions to control autoimmune diseases and graft vs. host disease, but oversuppression of these pathways may also lead to increased viral susceptibility and/or decreased tumor cell killing.
SURFACE ROUGHENING OF HETEROEPITAXIAL THIN FILMS
Authors: Gao Huajian , Nix William D.
Published: July 2002

▪ Abstract  Heteroepitaxial structures with strained semiconductor thin films are widely used in electronic and optoelectronic devices. One of the more important defect creation processes in these films is related to a stress-induced morphological instability that tends to roughen the film surface by mass diffusion during film growth or annealing. Interestingly, the same mechanism of surface roughening can be utilized for fabrication of quantum dot devices. This article gives an overview of a series of theoretical and experimental studies on surface roughening in heteroepitaxial films. It is shown that the strain caused by lattice mismatch drives the diffusional atomic flux along the film surface in such a way that an initially flat film evolves into an undulating profile with cusp-like surface valleys with singular stress concentration near the cusp tip. The essential features of this evolution process are described by a family of mathematical curves called cycloids. The fundamental length and time scales associated with surface roughening can be obtained from thermodynamic and kinetic considerations. The stress concentration at cycloid-like surface valleys caused by roughening is found to create dislocations of various characters that participate in the overall strain relaxation of a heterostructure.
Proliferation and the Monoclonal Origins of Atherosclerotic Lesions
Authors: Schwartz S.M. , Murry C.E.
Published: July 2002

Benditt's observation of the monoclonal origin of the atherosclerotic lesion has been controversial because it appeared to conflict with conventional wisdom. A new method based on a polymerase chain reaction amplification of the DNA of an X-inactivated gene from microdissected tissue confirms that Benditt was correct. However, this monoclonal expansion can also be found in nonatherosclerotic intima and media. These new data suggest that plaque clonality may represent expansion of preexisting patches of cells arising during development of the media. This developmental view does not conflict with other recent evidence that plaque expansion is associated with mutation or viral events. However, if plaques arise from patches, then early developmental mechanisms may be critical to the later evolution of the lesions.
Heparin-Induced Thrombocytopenia: A Ten-Year Retrospective
Authors: Warkentin, MD Theodore E.
Published: July 2002

The past decade has seen many important advances in the pathogenesis, clinical and laboratory diagnosis, and management of heparin-induced thrombocytopenia (HIT), one of the most common immune-mediated adverse drug reactions. HIT is caused by IgG antibodies that recognize complexes of heparin and platelet factor 4, leading to platelet activation via platelet FcγIIa receptors. Formation of procoagulant, platelet-derived microparticles, and, possibly, activation of endothelium generate thrombin in vivo. Thrombin generation helps to explain the strong association between HIT and thrombosis, including the newly recognized syndrome of warfarin-induced venous limb gangrene. This syndrome occurs when acquired protein C deficiency during warfarin treatment of HIT and deep venous thrombosis leads to the inability to regulate thrombin generation in the microvasculature. The central role of HIT antibodies in causing HIT, as well as refinements in laboratory assays to detect these antibodies, means that HIT should be considered a clinicopathologic syndrome. The diagnosis can be made confidently when one or more typical clinical events (most frequently, thrombocytopenia with or withoutt thrombosis) occur in a patient with detectable HIT antibodies. The central role of thrombin generation in this syndrome provides a rationale for the use of anticoagulants that reduce thrombin generation (danaparoid) or inhibit thrombin (lepirudin).
Coronary Artery Disease in the Transplanted Heart
Authors: Weis M. , von Scheidt W.
Published: July 2002

Coronary artery disease in the transplanted heart limits the long-term success of cardiac transplantation. Intravascular ultrasound studies reveal a dual morphology with donor-transmitted and de novo plaques. Coronary vasomotor dysfunction may occur independently of morphological alterations. The disease is characterized by the interaction of activated T lymphocytes with cytokines and donor epicardial and microvascular endothelium. Various noxious stimuli contribute to the continuing inflammatory response. Consequently, adhesion molecule expression is upregulated, leukocytes migrate into the allograft, thrombocytes accumulate, and growth factors are expressed, finally resulting in functional and morphological chronic allograft lesions. Blocking the activation of T cells, CD4+ cytokines, and adhesion molecules may prevent endothelial injury and subsequent intimal thickening. Strategies to decrease the formation of antiendothelial and anti-HLA-DR antibodies may also be protective, as may antiproliferative drugs, augmentation of endogenous nitric oxide bioactivity, and new immunosuppressive regimens. Revascularization procedures have a limited role in treating significant focal lesions. Retransplantation, the only definitive treatment, remains ethically controversial.
TOWARDS A UNIFIED EVOLUTIONARY GENETICS OF MICROORGANISMS
Authors: Tibayrenc M.
Published: July 2002

I propose here that evolutionary genetics, apart from improving our basic knowledge of the taxonomy and evolution of microbes (either eukaryotes or prokaryotes), can also greatly contribute to applied research in microbiology. Evolutionary genetics provides convenient guidelines for better interpreting genetic and molecular data dealing with microorganisms. The three main potential applications of evolutionary genetics in microbiology are (a) epidemiological follow-up (with the necessity of evaluating the stability off microbial genotypes over space and time); (b) taxonomy in the broad sense (better definition and sharper delimitation of preesently described taxa, research of hidden genetic subdivisions); and ( c) evaluation of the impact of the genetic diversity of microbes on their relevant properties (pathogenicity, resistance to drugs, etc). At present, two main kinds of population structure can be distinguished in natural microbial populations: (a) species that are not subdivided into discrete phylogenetic lineages (panmictic species or basically sexual species witth occasional bouts of short-term clonality fall into this category); (b) species that are strongly subdivided by either cryptic speciation or clonal evolution.

Improvements in available statistical methods are required to refine these distinctions and to better quantify the actual impact of gene exchange in natural microbial populations. Moreover, a codified selection of markers with appropriate molecular clocks (in other words: adapted levels of resolution) is sorely needed to answer distinct questions that address different scales of time and space: experimental, epidemic, and evolutionary. The problems raised by natural genetic diversity are very similar for all microbial species, in terms of both basic and applied science. Despite this fact, a regrettable compartmentalization among specialists has hampered progress in this field. I propose a synthetic approach, relying on the statistical improvements and technical standardizations called for above, to settle a unified evolutionary genetics of microorganisms, valid whatever the species studied, whether eukaryotic (parasitic protozoa and fungi) or prokaryotic (bacteria). Apart from benefits for basic evolutionary research, the anticipated payoff from this synthetic approach is to render routine and commonplace the use of microbial evolutionary genetics in the fields of epidemiology, medicine, and agronomy.
TRANSCRIPTIONAL CONTROL OF THE PSEUDOMONAS TOL PLASMID CATABOLIC OPERONS IS ACHIEVED THROUGH AN INTERPLAY OF HOST FACTORS AND PLASMID-ENCODED REGULATORS
Authors: Ramos Juan L. , Marqués Silvia , Timmis Kenneth N.
Published: July 2002

▪ Abstract  The xyl genes of Pseudomonas putida TOL plasmid that specify catabolism of toluene and xylenes are organized in four transcriptional units: the upper-operon xylUWCAMBN for conversion of toluene/xylenes into benzoate/alkylbenzoates; the meta-operon xylXYZLTEGFJQKIH, which encodes the enzymes for further conversion of these compounds into Krebs cycle intermediates; and xylS and xylR, which are involved in transcriptional control. The XylS and XylR proteins are members of the XylS/AraC and NtrC families, respectively, of transcriptional regulators. The xylS gene is constitutively expressed at a low level from the Ps2 promoter. The XylS protein is activated by interaction with alkylbenzoates, and this active form stimulates transcription from Pm by σ70- or σS-containing RNA polymerase (the meta loop). The xylR gene is also expressed constitutively. The XylR protein, which in the absence of effectors binds in a nonactive form to target DNA sequences, is activated by aromatic hydrocarbons and ATP; it subsequently undergoes multimerization and structural changes that result in stimulation of transcription from Pu of the upper operon. This latter process is assisted by the IHF protein and mediated by σ54-containing RNA polymerase. Once activated, the XylR protein also stimulates transcription from the Ps1 promoter of xylS without interfering with expression from Ps2. This process is assisted by the HU protein and is mediated by σ54-containing RNA polymerase. As a consequence of hyperexpression of the xylS gene, the XylS protein is hyperproduced and stimulates transcription from Pm even in the absence of effectors (the cascade loop). The two σ54-dependent promoters are additionally subject to global (catabolite repression) control.
CORTICAL PLASTICITY: From Synapses to Maps
Authors: Buonomano Dean V. , Merzenich Michael M.
Published: July 2002

▪ Abstract  It has been clear for almost two decades that cortical representations in adult animals are not fixed entities, but rather, are dynamic and are continuously modified by experience. The cortex can preferentially allocate area to represent the particular peripheral input sources that are proportionally most used. Alterations in cortical representations appear to underlie learning tasks dependent on the use of the behaviorally important peripheral inputs that they represent. The rules governing this cortical representational plasticity following manipulations of inputs, including learning, are increasingly well understood.

In parallel with developments in the field of cortical map plasticity, studies of synaptic plasticity have characterized specific elementary forms of plasticity, including associative long-term potentiation and long-term depression of excitatory postsynaptic potentials. Investigators have made many important strides toward understanding the molecular underpinnings of these fundamental plasticity processes and toward defining the learning rules that govern their induction. The fields of cortical synaptic plasticity and cortical map plasticity have been implicitly linked by the hypothesis that synaptic plasticity underlies cortical map reorganization. Recent experimental and theoretical work has provided increasingly stronger support for this hypothesis. The goal of the current paper is to review the fields of both synaptic and cortical map plasticity with an emphasis on the work that attempts to unite both fields. A second objective is to highlight the gaps in our understanding of synaptic and cellular mechanisms underlying cortical representational plasticity.
FROM BIOPHYSICS TO MODELS OF NETWORK FUNCTION
Authors: Marder Eve
Published: July 2002

▪ Abstract  Neurons and synapses display a rich range of time-dependent processes. Which of these are critical to understanding specific integrative functions in the brain? Computational methods of various kinds are used to understand how systems of neurons interact to produce behavior. However, these models often assume that neuronal dynamics and synaptic strengths are fixed. This review presents some recent models that illustrate that short-term synaptic plasticity mechanisms such as facilitation and depression can have important implications for network function. Other features of synaptic transmission such as multi-component synaptic potentials, cotransmission, and neuromodulation with obvious potential computational implications are presented. These examples illustrate that synaptic strength and intrinsic properties in networks are continuously varying on numerous time scales as a function of the temporal patterns of activity in the network. Thus, both firing frequency of the neurons in a circuit, and the modulatory environment determine the intrinsic and synaptic properties that produce behavior.
Touch and Go: Decision-Making Mechanisms in Somatosensation
Authors: Romo Ranulfo , Salinas Emilio
Published: July 2002

▪ Abstract  A complex sequence of neural events unfolds between sensory receptor activation and motor activity. To understand the underlying decision-making mechanisms linking somatic sensation and action, we ask what components of the neural activity evoked by a stimulus are directly related to psychophysical performance, and how are they related. We find that single-neuron responses in primary and secondary somatosensory cortices account for the observed performance of monkeys in vibrotactile discrimination tasks, and that neuronal and behavioral responses covary in single trials. This sensory activity, which provides input to memory and decision-making mechanisms, is modulated by attention and behavioral context, and microstimulation experiments indicate that it may trigger normal perceptual experiences. Responses recorded in motor areas seem to reflect the output of decision-making operations, which suggests that the ability to make decisions occurs at the sensory-motor interface.
ATOMIC PARITY NONCONSERVATION AND NUCLEAR ANAPOLE MOMENTS
Authors: Haxton W. C. , Wieman C. E.
Published: July 2002

▪ Abstract  Anapole moments are parity-odd, time-reversal-even moments of the E1 projection of the electromagnetic current. Although it was recognized, soon after the discovery of parity violation in the weak interaction, that elementary particles and composite systems such as nuclei must have anapole moments, it proved difficult to isolate this weak radiative correction. The first successful measurement, an extraction of the nuclear anapole moment of 133Cs from the hyperfine dependence of the atomic parity violation, was obtained only recently. An important anapole moment bound in thallium also exists. We discuss these measurements and their significance as tests of the hadronic weak interaction, focusing on the mechanisms that operate within the nucleus to generate the anapole moment. The atomic results place new constraints on weak meson-nucleon couplings, constraints we compare to existing bounds from a variety of [Formula: see text] and nuclear tests of parity nonconservation.
VITAMIN B12 DEFICIENCY IN THE ELDERLY
Authors: Baik H.W. , Russell R.M.
Published: July 2002

▪ Abstract  Vitamin B12 deficiency is estimated to affect 10%–15% of people over the age of 60, and the laboratory diagnosis is usually based on low serum vitamin B12 levels or elevated serum methylmalonic acid and homocysteine levels. Although elderly people with low vitamin B12 status frequently lack the classical signs and symptoms of vitamin B12 deficiency, e.g. megaloblastic anemia, precise evaluation and treatment in this population is important. Absorption of crystalline vitamin B12 does not decline with advancing age. However, compared with the younger population, absorption of protein-bound vitamin B12 is decreased in the elderly, owing to a high prevalence of atrophic gastritis in this age group. Atrophic gastritis results in a low acid-pepsin secretion by the gastric mucosa, which in turn results in a reduced release of free vitamin B12 from food proteins. Furthermore, hypochlorhydria in atrophic gastritis results in bacterial overgrowth of the stomach and small intestine, and these bacteria may bind vitamin B12 for their own use. The ability to absorb crystalline vitamin B12 remains intact in older people with atrophic gastritis. The 1998 recommended daily allowance for vitamin B12 is 2.4 μg, but elderly people should try to obtain their vitamin B12 from either supplements or fortified foods (e.g. fortified ready-to-eat breakfast cereals) to ensure adequate absorption from the gastrointestinal tract. Because the American food supply is now being fortified with folic acid, concern is increasing about neurologic exacerbation in individuals with marginal vitamin B12 status and high-dose folate intake.
THE GENETICS OF FATTY ACID METABOLISM IN SACCHAROMYCES CEREVISIAE
Authors: Trotter Pamela J
Published: July 2002

▪ Abstract  Long-chain fatty acids are a vital metabolic energy source and are building blocks of membrane lipids. The yeast Saccharomyces cerevisiae is a valuable model system for elucidation of gene-function relationships in such eukaryotic processes as fatty acid metabolism. Yeast degrades fatty acids only in the peroxisome, and recently, genes encoding core and auxiliary enzymes of peroxisomal β-oxidation have been identified. Mechanisms involved in fatty acid induction of gene expression have been described, and novel fatty acid–responsive genes have been discovered via yeast genome analysis. In addition, a number of genes essential for synthesis of the variety of fatty acids in yeast have been cloned. Advances in understanding such processes in S. cerevisiae will provide helpful insights to functional genomics approaches in more complex organisms.
THE TOXICOLOGY OF ENVIRONMENTAL TOBACCO SMOKE
Authors: Witschi Hanspeter , Joad Jesse P. , Pinkerton Kent E.
Published: July 2002

▪ Abstract  It has by now become obvious that environmental tobacco smoke (ETS) may pose a health risk to nonsmokers. Epidemiological data suggest that exposure to ETS may increase the risk of developing lung cancer, cardiovascular disease, intrauterine growth retardation, predisposition to chronic lung disease, and sudden infant death syndrome. The human populations most at risk from ETS exposure appear to be neonates, young children, and possibly the fetus while in utero. Experimental studies with cigarette sidestream smoke (SS) have successfully duplicated several of these disease conditions in laboratory animals, particularly the effects of SS on fetal growth, lung maturation, and altered airway reactivity. The availability of animal models may open the way to fruitful experimental studies on mechanisms that help us to better understand disease.
THEORY AND PRACTICE OF NUCLEAR SPIN RELAXATION IN PROTEINS
Authors: Dayie Kwaku T. , Wagner Gerhard , Lefèvre Jean-François
Published: July 2002

▪ Abstract  NMR relaxation experiments can provide information on overall and internal motions in proteins. This review consists of a concise report on the evolution of the theories for nuclear relaxation followed by an overview of mathematical models for internal motions in proteins. Next, the method of spectral density mapping with recent developments is reviewed. This is followed by a discussion of pulse sequences for relaxation experiments. Finally, we review recent studies correlating relaxation parameters, in particular spectral density functions, with structural features of proteins and with results of molecular dynamics simulations.
IONIC EFFECTS BEYOND POISSON-BOLTZMANN THEORY
Authors: Vlachy Vojko
Published: July 2002

▪ Abstract  Polyelectrolytes are electrolytes asymmetric both in charge and size. Their properties in solution are dominated by Coulombic forces, and without a detailed understanding of these interactions, no interpretation of experimental data is possible. This paper is a review of recent developments in the theory of highly asymmetric electrolytes of spherical shape resembling surfactant micelles. Three different models are discussed: (a) the cell model, which is focused on the small ion-macroion interaction; (b) the model that treats the solution as an effective one-component fluid of macroions; and (c) the isotropic model, where the solution is represented as a mixture of charged spheres. Traditionally, the electrostatic interactions are accounted for via the solution of the Poisson-Boltzmann equation. This theory, however, ignores the fluctuations around the most probable distribution and may yield poor results for systems with multivalent ions. This paper focuses on developments beyond the Poisson-Boltzmann theory; the results of computer simulations and integral equation theories represent the major part of the review.
APPLICATIONS OF IMPULSIVE STIMULATED SCATTERING IN THE EARTH AND PLANETARY SCIENCES
Authors: Abramson E. H. , Brown J. M. , Slutsky L. J.
Published: July 2002

▪ Abstract  The elastic, thermodynamic, and transport properties of crystals and fluids at high temperature and pressure play a central role in the earth and planetary sciences as well as in a variety of technologies. These properties also constitute a principal experimental constraint on the description of intermolecular interactions at short distances. Aspects of “impulsive stimulated scattering,” when adapted to measurements in the diamond-anvil high-pressure cell, provide an approach to the determination of a subset of equilibrium and dynamic properties at high density.
New Technologies in Electron Spin Resonance
Authors: Freed Jack H.
Published: July 2002

New electron spin resonance (ESR) technologies have been developed, which have led to new and improved applications. (a) The development of two-dimensional Fourier transform (FT) ESR required spectrometers providing intense π/2 microwave pulses of very short (3–5 ns) duration, wide bandwidths, and very short dead times. It has enabled studies that resolve sophisticated details of molecular dynamics in complex fluids. (b) Methods that produce multiple quantum coherences by pulsed ESR now enable accurate measurements of large distances (>12Å). (c) One of the most important advances has been the extension of ESR to high magnetic fields and high frequencies. This has benefited from the utilization of quasi-optical methods, especially above 150 GHz. The greatly improved orientational resolution and the faster “snapshot” of motions that are provided by ESR at high frequencies enhance studies of molecular dynamics. The use of both high and lower frequencies enables one to unravel faster and slower modes from the complex dynamics of fluids and macromolecules. (d) The development of FT-ESR imaging required substantial pulsed field gradients lasting only 50–100 ns. ESR imaging is effective in studying diffusion in fluids. Areas for further development are also described.
INDUCED MEMBRANE HYPO/HYPER-MECHANOSENSITIVITY:A Limitation of Patch-Clamp Recording
Authors: Hamill Owen P. , McBride Don W.
Published: July 2002

▪ Abstract  Practical limitations of the patch-clamp technique when recording mechanogated membrane ion channels are considered. Mechanical overstimulation of the patch or the cell from excessive suction/pressure protocols induces morphological and functional changes. In particular, the plasma membrane becomes decoupled from the underlying cytoskeleton to form either membrane blebs (cell-attached) or ghosts (whole cell). As a consequence, a membrane ion channel may show either a decrease or an increase in its native mechanosensitivity or even acquire mechanosensitivity. The effect varies with ion channel and cell type and presumably arises because of a disruption of membrane-cytoskeleton interactions. We consider that such disruptions are a pathological consequence of excessive mechanical stress, either during or after seal formation, rather than an immutable consequence of patch-clamp recording. By careful attention to the suction/pressure protocols during sealing and throughout recording, such artifacts can be avoided.
EXCITATION-CONTRACTION COUPLING IN GASTROINTESTINAL AND OTHER SMOOTH MUSCLES
Authors: Bolton T. B. , Prestwich S. A. , Zholos A. V. , Gordienko D. V.
Published: July 2002

▪ Abstract  The main contributors to increases in [Ca2+]iand tension are the entry of Ca2+through voltage-dependent channels opened by depolarization or during action potential (AP) or slow-wave discharge, and Ca2+release from store sites in the cell by the action of IP3or by Ca2+-induced Ca2+-release (CICR). The entry of Ca2+during an AP triggers CICR from up to 20 or more subplasmalemmal store sites (seen as hot spots, using fluorescent indicators); Ca2+waves then spread from these hot spots, which results in a rise in [Ca2+]ithroughout the cell. Spontaneous transient releases of store Ca2+, previously detected as spontaneous transient outward currents (STOCs), are seen as sparks when fluorescent indicators are used. Sparks occur at certain preferred locations—frequent discharge sites (FDSs)—and these and hot spots may represent aggregations of sarcoplasmic reticulum scattered throughout the cytoplasm. Activation of receptors for excitatory signal molecules generally depolarizes the cell while it increases the production of IP3(causing calcium store release) and diacylglycerols (which activate protein kinases). Activation of receptors for inhibitory signal molecules increases the activity of protein kinases through increases in cAMP or cGMP and often hyperpolarizes the cell. Other receptors link to tyrosine kinases, which trigger signal cascades interacting with trimeric G-protein systems.
Structure and Regulation of Amiloride-Sensitive Sodium Channels
Authors: de la Rosa Diego Alvarez , Canessa Cecilia M. , Fyfe Gregor K. , Zhang Ping
Published: July 2002

▪ Abstract  Amiloride-sensitive Na+ channels constitute a new class of proteins known as the ENaC-Deg family of ion channels. All members in this family share a common protein structure but differ in their ion selectivity, their affinity for the blocker amiloride, and in their gating mechanisms. These channels are expressed in many tissues of invertebrate and vertebrate organisms where they serve diverse functions varying from Na+ absorption across epithelia to being the receptors for neurotransmitters in the nervous system. Here, we review progress made during the last years in the characterization, regulation, and cloning of new amiloride-sensitive Na+ channels.
Chloride Channels and Hepatocellular Function: Prospects for Molecular Identification
Authors: Li Xinhua , Weinman Steven A.
Published: July 2002

▪ Abstract  Hepatocytes possess chloride channels at the plasma membrane and in multiple intracellular compartments. These channels are required for cell volume regulation and acidification of intracellular organelles. Evidence also supports a role of chloride channels in modulation of apoptosis and cell growth. Swelling- and Ca2+-activated chloride channels have been identified in hepatocyte plasma membranes, and chloride channels have been observed in the membranes of lysosomes, endosomes, Golgi, endoplasmic reticulum, mitochondria, and the nucleus. This review summarizes the functions of these channels and discusses the specific channel molecules they may represent. Chloride channel molecules shown to be expressed in hepatocytes include members of the ClC channel family (ClC-2, ClC-3, ClC-5, and ClC-7), members of the newly identified CLIC family of intracellular chloride channels (CLIC-1 and CLIC-4), the mitochondrial voltage-dependent anion channel, and a newly identified intracellular channel, MCLC (Mid-1 related chloride channel). Current understanding does not include a molecular identification of most of the observed channel functions, but details of the molecular properties of these channel molecules should allow future identification and further understanding of chloride channel function in hepatocytes.
MOLECULAR BIOLOGY OF RICE TUNGRO VIRUSES
Authors: Hull Roger
Published: July 2002

▪ Abstract  Rice tungro, the most important virus disease of rice in South and Southeast Asia, is caused by a complex of two viruses, rice tungro bacilliform virus (RTBV) and rice tungro spherical virus (RTSV). RTBV is a plant pararetrovirus with bacilliform particles, the structure of which is based on T = 3 icosahedral symmetry cut across the threefold axis.The particles encapsidate a circular double-stranded DNA of 8 kbp that encodes four proteins. The current information on the properties, functions, and expression of these proteins is discussed, as is the evidence for replication by reverse transcription. Two major strains of RTBV have been recognized, one from the Indian subcontinent and the other from Southeast Asia. RTSV particles contain a single-stranded RNA genome of 12 kb that encodes a large polyprotein and possibly one or two smaller proteins. The properties and processing of the polyprotein are described and the resemblance to picornaviruses noted.
BIOLOGY AND MOLECULAR BIOLOGY OF VIRUSES IN THE GENUS TENUIVIRUS
Authors: Falk Bryce W. , Tsai James H.
Published: July 2002

▪ Abstract  Viruses in the genus Tenuivirus (Tenuiviruses) cause a number of important diseases in economically important crop plants including rice and maize. Tenuiviruses are transmitted from plant to plant by specific planthopper vectors, and their transmission relationship is circulative-propagative. Thus, Tenuiviruses have host ranges including plants and animals (planthoppers). Four or five characteristic, circular ribonucleoprotein particles (RNPs), each containing a single Tenuivirus genomic RNA, can be isolated from Tenuivirus-infected plants. The genomic RNAs range in size from ca 9.0 kb to 1.3 kb and together give a total genome size of ca 18–19 kb. The genomic RNAs are either negative-sense or ambisense, and expression of the ambisense RNAs utilizes cap-snatching during mRNA transcription. The combination of characteristics exhibited by Tenuiviruses are quite different than those found for most plant viruses and are more similar to vertebrate-infecting viruses in the genus Phlebovirus of the Bunyaviridae.
DIVERSITY AMONG XANTHOMONADS PATHOGENIC ON PEPPER AND TOMATO
Authors: Jones J. B. , Stall R. E. , Bouzar H.
Published: July 2002

▪ Abstract  Xanthomonas campestris pv. vesicatoria, causal agent of bacterial spot of tomato and pepper, had been considered for nearly 70 years to be a relatively homogeneous organism. However, in the past decade this bacterium was determined to be composed of two genetically and phenotypically distinct groups. The two groups, designated A and B, were distinguished based on amylolytic activity, expression of unique protein bands, reaction on differential hosts (tomato races T1 and T2), reaction patterns with monoclonal antibodies, DNA restriction profiles, and DNA:DNA hybridization. The A and B groups were placed into X. axonopodis pv. vesicatoria and X. vesicatoria, respectively. A third group, designated C, was pathogenically (race T3) and serologically distinct from A and B strains, and formed unique DNA restriction profiles. DNA:DNA hybridization data suggest that C is distinct but related to A strains and may represent a subspecies of A. A final group, designated D, consisted of X. gardneri, an organism identified in Yugoslavia in 1957, and also found in Costa Rica. Group D was determined to be genetically distinct from strains within the other two groups; it represents a third Xanthomonas species pathogenic on tomato and pepper.
DOMESTIC POLITICS, FOREIGN POLICY, AND THEORIES OF INTERNATIONAL RELATIONS
Authors: Fearon James D.
Published: July 2002

▪ Abstract  A significant and growing literature on international relations (IR) argues that domestic politics is typically an important part of the explanation for states' foreign policies, and seeks to understand its influence more precisely. I argue that what constitutes a “domestic-political” explanation of a state's foreign policy choices has not been clearly elaborated. What counts as a domestic-political explanation is defined by opposition to systemic or structural explanations. But these may be specified in several different ways—I spell out two—each of which implies a different concept of domestic-political explanations. If a systemic IR theory pictures states as unitary, rational actors, then a domestic-political explanation is one in which domestic-political interactions in at least one state yield a suboptimal foreign policy relative to some normative standard. Or, if a systemic IR theory pictures states as unitary, rational actors and also requires that attributes of particular states not enter the explanation, then a domestic-political explanation is any one that involves state characteristics other than relative power. Implications of each approach are developed, and examples from the literature are provided. I also address the question of whether there is a sharp distinction between a “systemic theory of international politics” and a “theory of foreign policy,” arguing that there is an important and natural sense in which they are the same.
Memory Systems in the Brain
Authors: Rolls Edmund T.
Published: July 2002

The operation of different brain systems involved in different types of memory is described. One is a system in the primate orbitofrontal cortex and amygdala involved in representing rewards and punishers, and in learning stimulus-reinforcer associations. This system is involved in emotion and motivation. A second system in the temporal cortical visual areas is involved in learning invariant representations of objects. A third system in the hippocampus is implicated in episodic memory and in spatial function. Fourth, brain systems in the frontal and temporal cortices involved in short term memory are described. The approach taken provides insight into the neuronal operations that take place in each of these brain systems, and has the aim of leading to quantitative biologically plausible neuronal network models of how each of these memory systems actually operates.
Telemedicine: A New Health Care Delivery System
Authors: Bashshur Rashid L. , Reardon Timothy G. , Shannon Gary W.
Published: July 2002

▪ Abstract  The resurgence of telemedicine can be attributed to its potential for addressing intransigent problems in health care, including limited accessibility, cost inflation, and uneven quality. After discussing definitions and the genesis of telemedicine, this review focuses on conceptual issues and an assessment of past research. The scope and methodological rigor necessary for sustained development and policy making have been limited in this area of research, owing to the nature of extant telemedicine projects and the lack of a comprehensive research strategy that specifies the objectives of telemedicine research regarding accessibility, cost, and quality. Research strategies and a framework for analysis are discussed. Without a commitment to the types of research objectives, framework, and strategy presented here, the considerable promise of telemedicine, as an innovative system of care, may not be fully realized.
Institutional Assets and Adaptability: NATO After the Cold War
Authors: Wallander Celeste A.
Published: July 2002

The puzzle of NATO's persistence is best addressed as part of a larger inquiry into institutional change. Institutions persist because they are costly to create and less costly to maintain, but this institutionalist argument is incomplete. Whether institutions adapt to change depends on whether their norms, rules, and procedures are specific or general assets and on whether the asset mix matches the kinds of security problems faced by their members. Assets specific to coping with external threats will not be useful for coping with problems of instability and mistrust, so alliances with only the former will disappear when threats disappear. Alliances that have specific institutional assets for dealing with instability and mistrust and general institutional assets will be adaptable to environments that lack threats. I assess these hypotheses in a test case of NATO's institutional assets during and after the Cold War.
Multiple Wh-Fronting
Authors: Grewendorf Günther
Published: July 2002

This article argues that overt multiple wh-fronting in languages like Bulgarian consists of moving a single wh-cluster to [Spec, CP]. The formation of wh-clusters is motivated by the assumption that wh-elements can act as landing sites for wh-movement due to morphological properties of wh-words. I further argue that languages such as Japanese constitute covert instances of this process of wh-cluster formation, accounting for intricate constraints on multiple wh-questions such as the so-called “additional-wh effect.” Another central claim of the article is that despite appearances, multiple wh-questions in German equally involve the formation of wh-clusters, which are shown to consist of one visible and one or more invisible wh-elements. This analysis provides a new account for the lack of “short” and the presence of “long” superiority effects in German.
Resumption, Movement, and Derivational Economy
Authors: Aoun Joseph , Choueiri Lina , Hornstein Norbert
Published: July 2002

This article investigates the interaction between resumption and movement. Lebanese Arabic distinguishes between true resumption, where a pronoun or an epithet phrase is related to an Ā -antecedent via Bind, and apparent resumption, where the pronoun or the epithet phrase is related to its Ā -antecedent via Move. Only apparent resumption displays reconstruction effects for scope and binding. As resumptives, strong pronouns and epithet phrases cannot be related to a quantificational antecedent unless they occur inside islands. We account for this Obviation Requirement as follows: (a) (true) resumption is a last resort device, (b) strong pronouns and epithet phrases in apparent resumption contexts are generated as appositive modifiers of a DP, which is fronted to an Ā -position, and (c) appositive modifiers are interpreted as independent clauses. Obviation is reduced to the inability of quantifiers to bind a pronominal element across sentential boundaries.
Multiple Verb Movement in ≠ Hoan
Authors: Collins Chris
Published: July 2002

I argue that verbal compounds in ≠ Hoan are derived from underlying structures similar to serial verb constructions. I show that the derivation crucially involves multiple verb movement, which is subject to the same kinds of locality constraints as other types of multiple movement. I show how the multiple verb movement analysis applies to a range of verbal compounds in ≠ Hoan.
Charting the Learning Path: Cues to Parameter Setting
Authors: Dresher Bezalel Elan
Published: July 2002

This article argues for an approach to grammar acquisition that builds on the cue-based parametric model of Dresher and Kaye (1990). On this view, acquisition proceeds by means of an ordered path, in which cues to parameters become progressively more abstract and grammar-internal. A learner does not attempt to match target forms (contra Gibson and Wexler 1994), but uses them as evidence for parameter setting. Cues are local, and there is no global fitness metric (contra Clark and Roberts 1993). Acquisition of representations and acquisition of grammar proceed together and cannot be decoupled in the manner of Tesar and Smolensky (1998).
Recognizing Guston (in four slips)
Authors: Cooper Harry
Published: July 2002

A thing is recognized only as it comes into existence. —Philip Guston, 1964