bluuebunny/crossref_metadata_2025 huggingface dataset:
SIGNAL-MEDIATED SORTING OF MEMBRANE PROTEINS BETWEEN THE ENDOPLASMIC RETICULUM AND THE GOLGI APPARATUS
Authors: Teasdale Rohan D. , Jackson Michael R.
Published: July 2002

Each organelle of the secretory pathway is required to selectively allow transit of newly synthesized secretory and plasma membrane proteins and also to maintain a unique set of resident proteins that define its structural and functional properties. In the case of the endoplasmic reticulum (ER), residency is achieved in two ways: (a) prevention of residents from entering newly forming transport vesicles and (b) retrieval of those residents that escape. The latter mechanism is directed by discrete retrieval motifs: Soluble proteins have a H/KDEL sequence at their carboxy-terminus; membrane proteins have a dibasic motif, either di-lysine or di-arginine, located close to the terminus of their cytoplasmic domain. Recently it was found that di-lysine motifs bind the complex of cytosolic coat proteins, COP I, and that this interaction functions in the retrieval of proteins from the Golgi to the ER. Also discussed are the potential roles this interaction may have in vesicular trafficking.
MOLECULAR AND FUNCTIONAL ANALYSIS OF CADHERIN-BASED ADHERENS JUNCTIONS
Authors: Yap Alpha S. , Brieher William M. , Gumbiner Barry M.
Published: July 2002

▪ Abstract  Adherens junctions are specialized forms of cadherin-based adhesive contacts important for tissue organization in developing and adult organisms. Cadherins form protein complexes with cytoplasmic proteins (catenins) that convert the specific, homophilic-binding capacity of the extracellular domain into stable cell adhesion. The extracellular domains of cadherins form parallel dimers that possess intrinsic homophilic-binding activity. Cytoplasmic interactions can influence the function of the ectodomain by a number of potential mechanisms, including redistribution of binding sites into clusters, providing cytoskeletal anchorage, and mediating physiological regulation of cadherin function. Adherens junctions are likely to serve specific, specialized functions beyond the basic adhesive process. These functions include coupling cytoskeletal force generation to strongly adherent sites on the cell surface and the regulation of intracellular signaling events.
ERM-Merlin and EBP50 Protein Families in Plasma Membrane Organization and Function
Authors: Bretscher Anthony , Chambers David , Nguyen Rachel , Reczek David
Published: July 2002

▪ Abstract  The ezrin-radixin-moesin (ERM) family of proteins have emerged as key regulatory molecules in linking F-actin to specific membrane proteins, especially in cell surface structures. Merlin, the product of the NF2 tumor suppressor gene, has sequence similarity to ERM proteins and binds to some of the same membrane proteins, but lacks a C-terminal F-actin binding site. In this review we discuss how ERM proteins and merlin are negatively regulated by an intramolecular association between their N- and C-terminal domains. Activation of at least ERM proteins can be accomplished by C-terminal phosphorylation in the presence of PIP2. We also discuss membrane proteins to which ERM and merlin bind, including those making an indirect linkage through the PDZ-containing adaptor molecules EBP50 and E3KARP. Finally, the function of these proteins in cortical structure, endocytic traffic, signal transduction, and growth control is discussed.
Identification of Self Through Two-Dimensional Chemistry and Synapses
Authors: Dustin Michael L. , Bromley Shannon K. , Davis Mark M. , Zhu Cheng
Published: July 2002

▪ Abstract  Cells in the immune and nervous systems communicate through informational synapses. The two-dimensional chemistry underlying the process of synapse formation is beginning to be explored using fluorescence imaging and mechanical techniques. Early analysis of two-dimensional kinetic rates (konand koff) and equilibrium constants (Kd) provides a number of biological insights. First, there are two regimes for adhesion—one disordered with slow konand the other self-ordered with 104-fold faster kon. Despite huge variation in two-dimensional kon, the two-dimensional koffis like koffin solution, and two-dimensional koffis more closely related to intrinsic properties of the interaction than the two-dimensional kon. Thus difference in koffcan be used to set signaling thresholds. Early signaling complexes are compartmentalized to generate synergistic signaling domains. Immune antigen receptor components have a role in neural synapse editing. This suggests significant parallels in informational synapse formation based on common two-dimensional chemistry and signaling strategies.
BETA PICTORIS: An Early Solar System?
Authors: Artymowicz Pawel
Published: July 2002

▪ Abstract  Beta Pictoris (βPic) is the best studied of the normal main-sequence stars surrounded by circumstellar dust disks. We review the status of βPic and its disk, and compare it with both the early and the present Solar System. The disk has very little gas and therefore is more evolved and older than the primordial solar nebulae, which persist for 1–10 Myr. We concentrate on the observed optical properties, spatial and size distribution, mineralogy, and physics of the dust component, all of which are similar, if not identical, to those of the interplanetary and cometary dust in the Solar System. The most important process in the disk is collisional fragmentation of orbiting solid bodies, leading to the eventual removal of micron-sized and smaller debris from the system by radiation pressure. Silicate dust and sand, as well as planetesimals (perhaps comets) are observed around the star in quantities that are orders of magnitude larger than those in the present Solar System, but are consistent with a young solar system in the clearing stage. Theory of the βPic disk indicates that its age must be <100 Myr, and its mass comparable with that of all solid bodies in our system. Several indirect arguments support the hypothetical existence of planet(s) in orbit around the star. Our current knowledge strongly suggests a positive answer to the title question.
HYDROCHEMISTRY OF FORESTED CATCHMENTS
Authors: Church M. Robbins
Published: July 2002

“The song of a river ordinarily means the tune that waters play on rock, root, and rapid. …This song of the waters is audible to every ear, but there is other music in these hills, by no means audible to all. To hear even a few notes of it you must first live here for a long time, and you must know the speech of hills and rivers. Then on a still night, when the campfire is low and the Pleiades have climbed over rimrocks, sit quietly and listen for a wolf to howl, and think hard of everything you have seen and tried to understand. Then you may hear it—a vast pulsing harmony—its score inscribed on a thousand hills, its notes the lives and deaths of plants and animals, its rhythms spanning the seconds and the centuries.” Aldo Leopold, Song of the Gavilan [Reprinted in part from ( Leopold (1940) , by permission of The Wildlife Society.]

▪ Abstract  The pathways that water may take through a catchment and its reactions with organisms and soils are myriad and ever varying. A promising means to unraveling the mystery of watershed hydrochemistry is the study of “small” catchments, yet the hydrochemical function of even the smallest of catchments involves an amazingly intricate web of flowpaths and biogeochemical processes. Monitoring of catchments and comparison of their inputs to their outputs yields clues to their workings. Manipulation of catchments offers some means of “controlled” experimentation as to their nature. Modeling of catchment hydrochemical response attempts to put it all together. Every forested catchment is individual in its structure and hydrochemical response, yet a select, carefully studied few often are drafted to serve as representatives in assessments of responses to environmental influences or perturbations (e.g. acid rain). Many factors must be considered in such extrapolations. Studies of forested catchments often are driven by environmental concerns and thus fluctuate accordingly as to their location and intensity. Despite such fluctuations, the future of the field is clear and bright. Much has been learned as a result of recent studies, not only of what to think about catchment function but, more importantly, how to think about it.
The Late Ordovician Mass Extinction
Authors: Sheehan Peter M
Published: July 2002

▪ Abstract  Near the end of the Late Ordovician, in the first of five mass extinctions in the Phanerozoic, about 85% of marine species died. The cause was a brief glacial interval that produced two pulses of extinction. The first pulse was at the beginning of the glaciation, when sea-level decline drained epicontinental seaways, produced a harsh climate in low and mid-latitudes, and initiated active, deep-oceanic currents that aerated the deep oceans and brought nutrients and possibly toxic material up from oceanic depths. Following that initial pulse of extinction, surviving faunas adapted to the new ecologic setting. The glaciation ended suddenly, and as sea level rose, the climate moderated, and oceanic circulation stagnated, another pulse of extinction occurred. The second extinction marked the end of a long interval of ecologic stasis (an Ecologic-Evolutionary Unit). Recovery from the event took several million years, but the resulting fauna had ecologic patterns similar to the fauna that had become extinct. Other extinction events that eliminated similar or even smaller percentages of species had greater long-term ecologic effects.
Geologic Structure of the Uppermost Oceanic Crust Created at Fast- to Intermediate-Rate Spreading Centers
Authors: Karson Jeffrey A.
Published: July 2002

▪ Abstract  Geological investigations of major fault scarps (“tectonic windows”) and DSDP/ODP Drill Holes provide direct views of the uppermost oceanic crust generated at fast- to intermediate-rate spreading centers. These areas reveal a consistent upper crustal structural geometry with basaltic lava flows defining a pattern of downward increasing (“inward”) dip toward the spreading center at which they formed and dikes in the lavas and underlying sheeted dike complex showing a similar degree of “outward” dip. Widespread fracturing, faulting, and hydrothermal metamorphism accompanied magmatic construction. These geological relationships can be interpreted in terms of dramatic, asymmetrical, subaxial subsidence of upper crustal rock units that diminishes across the very narrow (few kilometers wide) zone of lava accumulation and dike intrusion at the ridge axis. This type of crustal structure is in accord with some existing models of spreading but augments these idealized views with more realistic geological complexity.
Ecological Resilience—In Theory and Application
Authors: Gunderson Lance H.
Published: July 2002

▪ Abstract  In 1973, C. S. Holling introduced the word resilience into the ecological literature as a way of helping to understand the non-linear dynamics observed in ecosystems. Ecological resilience was defined as the amount of disturbance that an ecosystem could withstand without changing self-organized processes and structures (defined as alternative stable states). Other authors consider resilience as a return time to a stable state following a perturbation. A new term, adaptive capacity, is introduced to describe the processes that modify ecological resilience. Two definitions recognize the presence of multiple stable states (or stability domains), and hence resilience is the property that mediates transition among these states. Transitions among stable states have been described for many ecosystems, including semi-arid rangelands, lakes, coral reefs, and forests. In these systems, ecological resilience is maintained by keystone structuring processes across a number of scales, sources of renewal and reformation, and functional biodiversity. In practice, maintaining a capacity for renewal in a dynamic environment provides an ecological buffer that protects the system from the failure of management actions that are taken based upon incomplete understanding, and it allows managers to affordably learn and change.
Invasion of Coastal Marine Communities in North America: Apparent Patterns, Processes, and Biases
Authors: Ruiz Gregory M. , Fofonoff Paul W. , Carlton James T. , Wonham Marjorie J. , Hines Anson H.
Published: July 2002

▪ Abstract  Biological invasions of marine habitats have been common, and many patterns emerge from the existing literature. In North America, we identify 298 nonindigenous species (NIS) of invertebrates and algae that are established in marine and estuarine waters, generating many “apparent patterns” of invasion: (a) The rate of reported invasions has increased exponentially over the past 200 years; (b) Most NIS are crustaceans and molluscs, while NIS in taxonomic groups dominated by small organisms are rare; (c) Most invasions have resulted from shipping; (d) More NIS are present along the Pacific coast than the Atlantic and Gulf coasts; (e) Native and source regions of NIS differ among coasts, corresponding to trade patterns. The validity of these apparent patterns remains to be tested, because strong bias exists in the data. Overall, the emergent patterns reflect interactive effects of propagule supply, invasion resistance, and sampling bias. Understanding the relative contribution of each component remains a major challenge for invasion ecology and requires standardized, quantitative measures in space and time that we now lack.
ANTHROPOGENIC MOBILIZATION OF SULPHUR AND NITROGEN: Immediate and Delayed Consequences
Authors: Galloway James N.
Published: July 2002

▪ Abstract  Global mobilization and dispersal of sulphur (S) and nitrogen (N) have been significantly increased by human activities. They are projected to increase even more in the future owing to growth in population and per-capita consumption of food and energy in the developing world, primarily Asia. Increased mobilization and distribution result in changes in precipitation acidity, ecosystem alkalinity and nutrient status, tropospheric and stratospheric ozone concentrations, and energy balance of the troposphere. Although increases in S and N mobilization cause increased environmental impacts, a leveling or decrease in mobilization does not result in a lessening of environmental impacts because of the accumulation of reactive S and N in environmental reservoirs. As S and N accumulate, ecosystems become saturated and S and N dispersal increases. Environmental impacts will only begin to lessen if mobilization rates decrease and as accumulated reactive S and N are converted to nonreactive forms or stored in long-term reservoirs.
AN ASSESSMENT OF WORLD HYDROCARBON RESOURCES
Authors: Rogner H-H.
Published: July 2002

▪ Abstract  Assessments of global coal, oil, and natural gas occurrences usually focus on conventional hydrocarbon reserves, i.e. those occurrences that can be exploited with current technology and present market conditions. The focus on reserves seriously underestimates long-term global hydrocarbon availability. Greenhouse gas emissions based on these estimates may convey the message that the world is running out of fossil fuels, and as a result, emissions would be reduced automatically. If the vast unconventional hydrocarbon occurrences are included in the resource estimates and historically observed rates of technology change are applied to their mobilization, the potential accessibility of fossil sources increases dramatically with long-term production costs that are not significantly higher than present market prices. Although the geographical hydrocarbon resource distribution varies significantly, a regional breakdown for 11 world regions indicates that neither hydrocarbon resource availability nor costs are likely to become forces that automatically would help wean the global energy system from the use of fossil fuel during the next century.
PHOSPHORUS IN THEENVIRONMENT: Natural Flows and Human Interferences
Authors: Smil Vaclav
Published: July 2002

▪ Abstract  Phosphorus has a number of indispensable biochemical roles, but it does not have a rapid global cycle akin to the circulations of C or N. Natural mobilization of the element, a part of the grand geotectonic denudation-uplift cycle, is slow, and low solubility of phosphates and their rapid transformation to insoluble forms make the element commonly the growth-limiting nutrient, particularly in aquatic ecosystems. Human activities have intensified releases of P. By the year 2000 the global mobilization of the nutrient has roughly tripled compared to its natural flows: Increased soil erosion and runoff from fields, recycling of crop residues and manures, discharges of urban and industrial wastes, and above all, applications of inorganic fertilizers (15 million tonnes P/year) are the major causes of this increase. Global food production is now highly dependent on the continuing use of phosphates, which account for 50–60% of all P supply; although crops use the nutrient with relatively high efficiency, lost P that reaches water is commonly the main cause of eutrophication. This undesirable process affects fresh and ocean waters in many parts of the world. More efficient fertilization can lower nonpoint P losses. Although P in sewage can be effectively controlled, such measures are often not taken, and elevated P is common in treated wastewater whose N was lowered by denitrification. Long-term prospects of inorganic P supply and its environmental consequences remain a matter of concern.
HISTORICAL AND FUTURE TRENDS IN AIRCRAFT PERFORMANCE, COST, AND EMISSIONS
Authors: Lee Joosung J. , Lukachko Stephen P. , Waitz Ian A. , Schafer Andreas
Published: July 2002

▪ Abstract  The interdependency of aircraft technological systems, the global reach of the aviation transport industry, and the uncertainty surrounding potential atmospheric effects have made defining the relationship between aviation and environmental impact an arduous task. Air travel continues to experience the fastest growth of all modes of transport, and although the energy intensity of the aviation transport system continues to decline, fuel use and total emissions have steadily risen. This trend, which represents a conflict between growth and environmental impact, has motivated the aircraft manufacturing and airline industries, the scientific community, and governmental bodies to consider what pace of emissions reduction is acceptable. This paper analyzes the historical influence of aircraft performance on cost to examine the potential pace of future efficiency improvements and emissions reduction. Technological and operational influences on aircraft energy intensity are quantified and correlated with direct operating cost and aircraft price using analytical and statistical models built upon historical data for US airlines. The energy intensity reduction potential and economic characteristics of future aircraft are also projected, through extrapolations of historical trends in aircraft technology and operations.
INTERACTIONS AMONG SCOLYTID BARK BEETLES, THEIR ASSOCIATED FUNGI, AND LIVE HOST CONIFERS
Authors: Paine T. D. , Raffa K. F. , Harrington T. C.
Published: July 2002

▪ Abstract  Scolytid bark beetles that colonize living conifers are frequently associated with specific fungi that are carried in specialized structures or on the body surface. These fungi are introduced into the tree during the attack process. The continuing association suggests that there is mutual benefit to the fitness of both beetles and fungi. The fungal species may benefit from the association with the beetles by transport to new host trees. Beetle species may benefit from the association with fungi by feeding on the fungi, or by the fungi contributing to the death of the host trees through mycelial penetration of host tissue, toxin release, interactions with preformed and induced conifer defenses, or the combined action of both beetles and fungi during colonization. Extensive research has been directed towards characterizing the interactions of beetle-fungal complexes with live host conifers and determining the ecological advantages for maintaining the associations. However, differences among systems and how species interact under different population and environmental conditions make it difficult to generalize about the importance of the separate biological components in successful host colonization.
Life Systems of Polyphagous Arthropod Pests in Temporally Unstable Cropping Systems
Authors: Kennedy George G. , Storer Nicholas P.
Published: July 2002

▪ Abstract  Annual cropping systems consist of a shifting mosaic of habitats that vary through time in their availability and suitability to insect pests. Agroecosystem instability results from changes that occur within a season with crop planting, development, and harvest. Further instability results from continuous alterations in biotic and abiotic insect life system components and from agricultural inputs. Changes to agroecosystems occur across seasons with changing agricultural practices, changing cropping patterns, and technological innovations. Much of this instability is a result of events unconnected with pest management.

The abilities of polyphagous pest species to move among and utilize different habitat patches in response to changes in suitability enable the pests to exploit unstable cropping systems. These pest characteristics determine the location and timing of damaging populations. Habitat suitability is influenced by plant species and cultivar, crop phenology, and agricultural inputs. Pest movement is affected by a suite of intrinsic factors, such as population age structure and mobility, and extrinsic factors, including weather systems and habitat distribution.

The life systems of three selected polyphagous pests are presented to demonstrate how an understanding of such systems in agricultural ecosystems improves our ability to predict and hence manage these populations.
BIOLOGICAL CONTROL OF LOCUSTS AND GRASSHOPPERS
Authors: Lomer C. J. , Bateman R. P. , Johnson D. L. , Langewald J. , Thomas M.
Published: July 2002

▪ Abstract  Control of grasshoppers and locusts has traditionally relied on synthetic insecticides, and for emergency situations this is unlikely to change. However, a growing awareness of the environmental issues associated with acridid control as well as the high costs of emergency control are expanding the demand for biological control. In particular, preventive, integrated control strategies with early interventions will reduce the financial and environmental costs associated with large-scale plague treatments. The recent development of effective oil formulations of Metarhizium anisopliae spores in Africa, Australia, and Brazil opens new possibilities for environmentally safe control operations. Metarhizium biopesticide kills 70%–90% of treated locusts within 14–20 days, with no measurable impact on nontarget organisms. An integrated pest management strategy, with an emphasis on the use of Metarhizium, that incorporates rational use of chemical pesticides with biological options such as the microsporidian Nosema locustae and the hymenopteran egg parasitoids Scelio spp., has become a realistic option.
CONVECTION INTO DOMAINS WITH OPEN BOUNDARIES
Authors: Maxworthy T.
Published: July 2002

▪ Abstract  Convection into regions with open, or partially-open, lateral boundaries is considered. The products of convectively-driven mixing can flow out from under the source generating a compensating inflow as they do so. The effects of rotation, ambient stratification and the geometry of the region on these flow quantities are considered, since all affect the density and velocity distributions that result. Three typical geometries are considered: convection into a channel or sea with an exit constriction; convection from a patch or strip into stratified and/or rotating surroundings and, finally, into a rotating coastal environment. In each case the simplest possible models are considered in the hope that they can offer some insight into the dynamical processes that affect the overall behaviour of each system. These are supplemented by reference to numerical and laboratory experiments as well as field observations. Finally suggestions for future work in the former two cases are presented in the hope that they will stimulate the reader's interest.
AIRPLANE TRAILING VORTICES
Authors: Spalart Philippe R.
Published: July 2002

▪ Abstract  This review surveys the formation, motion, and persistence of trailing vortices as relevant to the safety and productivity of air travel. It highlights findings or shifts made since Widnall's (1975) review in this series. This review also examines the predictability of the vortices (particularly in terms of lifespan), the durability of multiple vortex pairs, the controversy between expectations of vortex decay and of vortex collapse, the many types of turbulence that may influence the flow, the rich interplay between the rotational and the axial velocity fields in the vortex, the various atmospheric and ground-related factors that dominate the late behavior, a few instances of wakes rising back, and the still unexplained bursting of the vortices. The article also briefly covers prospects for detection and control.
LATTICE BOLTZMANN METHOD FOR FLUID FLOWS
Authors: Chen Shiyi , Doolen Gary D.
Published: July 2002

▪ Abstract  We present an overview of the lattice Boltzmann method (LBM), a parallel and efficient algorithm for simulating single-phase and multiphase fluid flows and for incorporating additional physical complexities. The LBM is especially useful for modeling complicated boundary conditions and multiphase interfaces. Recent extensions of this method are described, including simulations of fluid turbulence, suspension flows, and reaction diffusion systems.
BOILING HEAT TRANSFER
Authors: Dhir V. K.
Published: July 2002

▪ Abstract  This review examines recent advances made in predicting boiling heat fluxes, including some key results from the past. The topics covered are nucleate boiling, maximum heat flux, transition boiling, and film boiling. The review focuses on pool boiling of pure liquids, but flow boiling is also discussed briefly.
DIRECT NUMERICAL SIMULATION: A Tool in Turbulence Research
Authors: Moin Parviz , Mahesh Krishnan
Published: July 2002

▪ Abstract  We review the direct numerical simulation (DNS) of turbulent flows. We stress that DNS is a research tool, and not a brute-force solution to the Navier-Stokes equations for engineering problems. The wide range of scales in turbulent flows requires that care be taken in their numerical solution. We discuss related numerical issues such as boundary conditions and spatial and temporal discretization. Significant insight into turbulence physics has been gained from DNS of certain idealized flows that cannot be easily attained in the laboratory. We discuss some examples. Further, we illustrate the complementary nature of experiments and computations in turbulence research. Examples are provided where DNS data has been used to evaluate measurement accuracy. Finally, we consider how DNS has impacted turbulence modeling and provided further insight into the structure of turbulent boundary layers.
INERTIAL EFFECTS IN SUSPENSION AND POROUS-MEDIA FLOWS
Authors: Koch Donald L , Hill Reghan J
Published: July 2002

▪ Abstract  The current understanding of the average flow properties of packed beds and particle suspensions, in which inertia plays a significant role on the particle length scale, is examined. The features of inertial suspensions posing challenges to theoriticians include the nonlinear and unsteady nature of the governing equations, the inability to superimpose solutions, the prevalence of hydrodynamic instabilities, and the existence of particle-particle collisions. We discuss two special cases of inertial suspensions, for which detailed kinetic theories have been developed: (a) particles in a gas, and (b) spherical, high-Reynolds number bubbles in liquid. Subsequently, we review recent applications of computational fluid dynamics to simulate the motion in particle suspensions with both inertia and vorticity in the continueous phase. The synthesis of these analytical and numerical techniques is a promising approach to address the many challenges of modelling inertial suspensions.
MOLECULAR GENETICS OF SPORULATION IN BACILLUS SUBTILIS
Authors: Stragier Patrick , Losick Richard
Published: July 2002

▪ Abstract  The process of sporulation in the bacterium Bacillus subtilis proceeds through a well-defined series of morphological stages that involve the conversion of a growing cell into a two-cell-chamber sporangium within which a spore is produced. Over 125 genes are involved in this process, the transcription of which is temporally and spatially controlled by four DNA-binding proteins and five RNA polymerase sigma factors. Through a combination of genetic, biochemical, and cell biological approaches, regulatory networks have been elucidated that explicitly link the activation of these sigma factors to landmark events in the course of morphogenesis and to each other through pathways of intercellular communication. Signals targeting proteins to specific subcellular localizations and governing the assembly of macromolecular structures have been uncovered but their nature remains to be determined.
Plant Retrotransposons
Authors: Kumar Amar , Bennetzen Jeffrey L.
Published: July 2002

▪ Abstract  Retrotransposons are mobile genetic elements that transpose through reverse transcription of an RNA intermediate. Retrotransposons are ubiquitous in plants and play a major role in plant gene and genome evolution. In many cases, retrotransposons comprise over 50% of nuclear DNA content, a situation that can arise in just a few million years. Plant retrotransposons are structurally and functionally similar to the retrotransposons and retroviruses that are found in other eukaryotic organisms. However, there are important differences in the genomic organization of retrotransposons in plants compared to some other eukaryotes, including their often-high copy numbers, their extensively heterogeneous populations, and their chromosomal dispersion patterns. Recent studies are providing valuable insights into the mechanisms involved in regulating the expression and transposition of retrotransposons. This review describes the structure, genomic organization, expression, regulation, and evolution of retrotransposons, and discusses both their contributions to plant genome evolution and their use as genetic tools in plant biology.
TELOMERES AND THEIR CONTROL
Authors: McEachern Michael J , Krauskopf Anat , Blackburn Elizabeth H
Published: July 2002

▪ Abstract  Telomeres are DNA and protein structures that form complexes protecting the ends of chromosomes. Understanding of the mechanisms maintaining telomeres and insights into their function have advanced considerably in recent years. This review summarizes the currently known components of the telomere/telomerase functional complex, and focuses on how they act in the control of processes occurring at telomeres. These include processes acting on the telomeric DNA and on telomeric proteins. Key among them are DNA replication and elongation of one telomeric DNA strand by telomerase. In some situations, homologous recombination of telomeric and subtelomeric DNA is induced. All these processes act to replenish or restore telomeres. Conversely, degradative processes that shorten telomeric DNA, and nonhomologous end-joining of telomeric DNA, can lead to loss of telomere function and genomic instability. Hence they too must normally be tightly controlled.
THE SOS RESPONSE: Recent Insights into umuDC-Dependent Mutagenesis and DNA Damage Tolerance
Authors: Sutton Mark D , Smith Bradley T , Godoy Veronica G , Walker Graham C
Published: July 2002

▪ Abstract  Be they prokaryotic or eukaryotic, organisms are exposed to a multitude of deoxyribonucleic acid (DNA) damaging agents ranging from ultraviolet (UV) light to fungal metabolites, like Aflatoxin B1. Furthermore, DNA damaging agents, such as reactive oxygen species, can be produced by cells themselves as metabolic byproducts and intermediates. Together, these agents pose a constant threat to an organism's genome. As a result, organisms have evolved a number of vitally important mechanisms to repair DNA damage in a high fidelity manner. They have also evolved systems (cell cycle checkpoints) that delay the resumption of the cell cycle after DNA damage to allow more time for these accurate processes to occur. If a cell cannot repair DNA damage accurately, a mutagenic event may occur.

Most bacteria, including Escherichia coli, have evolved a coordinated response to these challenges to the integrity of their genomes. In E. coli, this inducible system is termed the SOS response, and it controls both accurate and potentially mutagenic DNA repair functions [reviewed comprehensively in ( 25 ) and also in ( 78 , 94 )]. Recent advances have focused attention on the umuD+C+-dependent, translesion DNA synthesis (TLS) process that is responsible for SOS mutagenesis ( 70 , 86 ). Here we discuss the SOS response of E. coli and concentrate in particular on the roles of the umuD+C+ gene products in promoting cell survival after DNA damage via TLS and a primitive DNA damage checkpoint.
POLYGENIC AND MULTIFACTORIAL DISEASE GENE ASSOCIATION IN MAN: Lessons from AIDS
Authors: O'Brien Stephen J. , Nelson George W. , Winkler Cheryl A. , Smith Michael W.
Published: July 2002

▪ Abstract  In an age when the majority of monogenic human disease genes have been identified, a particular challenge for the coming generation of human geneticists will be resolving complex polygenic and multifactorial diseases. The tools of molecular and population genetic association have much potential as well as peril in uncovering small cryptic genetic effects in disease. We have used a candidate gene approach to identify eight distinct human loci with alleles that in different ways influence the outcome of exposure to HIV-1, the AIDS virus. The successes in these gene hunts have validated the approach and illustrate the strengths and limitations of association analysis in an actual case history. The integration of genetic associations, well-described clinical cohorts, extensive basic research on AIDS pathogenesis, and functional interpretation of gene connections to disease offers a formula for detecting such genes in complex human genetic phenotypes.
Hundred-Year Search for the Human Genome
Authors: Ruddle Frank
Published: July 2002

The human genome has been an article of interest since the rediscovery of Mendel's laws at the turn of the century (1900–1901). Much progress was made during the first decade (1900–1910) with respect to our understanding of fundamental aspects of human genetics, such as the chromosomal basis of heredity, biochemical genetics, and population genetics. The development of these fields of inquiry languished for several decades but then advanced rapidly. However, human gene mapping stalled until 1970 when somatic cell genetic methods were introduced. The contributions of hybrid cell mapping to physical methods of genome analysis are described, and its legacy as an antecedent to the human genome initiative is discussed. Lastly, some properties of the 2000–2001 version of the human genome are briefly outlined.
ACCESSIBILITY CONTROL OF ANTIGEN-RECEPTOR VARIABLE-REGION GENE ASSEMBLY: Role ofcis-Acting Elements
Authors: Sleckman Barry P. , Gorman James R. , Alt Frederick W.
Published: July 2002

▪ Abstract  Antigen receptor variable region genes are assembled from germline variable (V), diversity (D), and joining (J) gene segments. This process requires expression of V(D)J recombinase activity, and “accessibility” of variable gene segments to this recombinase. The exact mechanism by which variable gene segments become accessible during development is not known. However, several studies have shown that cis-acting elements that regulate transcription may also function to regulate accessibility. Here we review the evidence that transcriptional promoters, enhancers, and silencers are involved in regulation of accessibility. The manner in which these elements may combine to regulate accessibility is addressed. In addition, current and potential strategies for identifying and analyzing cis-acting elements that mediate locus accessibility are discussed.
NEUTRALIZING ANTIVIRAL B CELL RESPONSES
Authors: Bachmann Martin F. , Zinkernagel Rolf M.
Published: July 2002

▪ Abstract  Neutralizing antiviral B cell responses differ in various aspects from the many usually measured B cell responses specific for protein in adjuvants. In particular, such neutralizing antiviral B cell responses are more rapidly induced, reach higher titers, are longer lived, and are efficiently generated without adjuvants. Evidence is summarized here that the repetitiveness of many viral antigens is a key factor responsible for the efficiency of these B cell responses, amplifying B cells early and rapidly for potent IgM responses and also for efficient switching to IgG. The data reviewed indicate that B cells discriminate antigen patterns via the degree of surface Ig-cross-linking and use antigen repetitiveness as a self/nonself discriminator.
ESCAPE OF HUMAN IMMUNODEFICIENCY VIRUS FROM IMMUNE CONTROL
Authors: McMichael Andrew J. , Phillips Rodney E.
Published: July 2002

▪ Abstract  Cytotoxic T lymphocytes (CTL) play a crucial role in the attempt to control infection with human immunodeficiency virus (HIV). Variation in epitopes recognized by CTL is common and frequently offers potential escape routes for mutant virus. Proof of escape, however, requires demonstration of increased frequency of virus particles or provirus that carry the escape sequence. There are now several recorded examples of virus variants that escape from CTL and are then selected. Most dramatic are those in which the CTL response has been dominated by CTL recognizing a single epitope that has suddenly changed, resulting in escape to fixation. This has been seen both early and late in the infection, leaving no doubt that escape occurs. Such escape is likely to be favored when the antiviral CTL response is oligoclonal and focused on a small number of immunodominant epitopes. The heterogeneous CTL response seen in many HIV-infected patients may result from successive waves of virus escape followed by new CTL responses specific for subdominant epitopes. Mutant virus can escape by several different routes, including failure of the mutated peptide to bind to the presenting HLA molecule and altered interactions with T cell receptors (TCR), including antagonism.
THE MULTIFACETED REGULATION OF INTERLEUKIN-15 EXPRESSION AND THE ROLE OF THIS CYTOKINE IN NK CELL DIFFERENTIATION AND HOST RESPONSE TO INTRACELLULAR PATHOGENS
Authors: Waldmann T. A. , Tagaya Y.
Published: July 2002

▪ Abstract  Interleukin-15 (IL-15) is a 14- to 15-kDa member of the 4 α-helix bundle family of cytokines. IL-15 expression is controlled at the levels of transcription, translation, and intracellular trafficking. In particular, IL-15 protein is posttranscriptionally regulated by multiple controlling elements that impede translation, including 12 upstream AUGs of the 5′ UTR, 2 unusual signal peptides, and the C-terminus of the mature protein. IL-15 uses two distinct receptor and signaling pathways. In T and NK cells the IL-15 receptor includes IL-2/15Rβ and γc, subunits, which are shared with IL-2, and an IL-15-specific receptor subunit, IL-15Rα. Mast cells respond to IL-15 with a receptor system that does not share elements with the IL-2 receptor but uses a novel 60- to 65-kDa IL-15RX subunit. In mast cells IL-15 signaling involves Jak2/STAT5 activation rather than the Jak1/Jak3 and STAT5/STAT3 system used in activated T cells. In addition to its other functional activities in immune and nonimmune cells, IL-15 plays a pivotal role in the development, survival, and function of NK cells. Abnormalities of IL-15 expression have been described in patients with rheumatoid arthritis or inflammatory bowel disease and in diseases associated with the retroviruses HIV and HTLV-I. New approaches directed toward IL-15, its receptor, or its signaling pathway may be of value in the therapy of these disorders.
Neuroendocrine Regulation of Immunity
Authors: Webster Jeanette I. , Tonelli Leonardo , Sternberg Esther M.
Published: July 2002

A reciprocal regulation exists between the central nervous and immune systems through which the CNS signals the immune system via hormonal and neuronal pathways and the immune system signals the CNS through cytokines. The primary hormonal pathway by which the CNS regulates the immune system is the hypothalamic-pituitary-adrenal axis, through the hormones of the neuroendocrine stress response. The sympathetic nervous system regulates the function of the immune system primarily via adrenergic neurotransmitters released through neuronal routes. Neuroendocrine regulation of immune function is essential for survival during stress or infection and to modulate immune responses in inflammatory disease. Glucocorticoids are the main effector end point of this neuroendocrine system and, through the glucocorticoid receptor, have multiple effects on immune cells and molecules. This review focuses on the regulation of the immune response via the neuroendocrine system. Particular details are presented on the effects of interruptions of this regulatory loop at multiple levels in predisposition and expression of immune diseases and on mechanisms of glucocorticoid effects on immune cells and molecules.
MATERIALS FOR FULL-COLOR ELECTROLUMINESCENT DISPLAYS
Authors: Ono Yoshimasa A.
Published: July 2002

▪ Abstract  New thin-film electroluminescent (EL) materials with blue and broadband emissions recently have been developed that meet the phosphor requirements for commercial multicolor and full-color EL display products. Improvements have been achieved in phosphor luminance, luminous efficiency, emission color, and aging characteristics. This paper reviews the latest advancements in red, green, and blue thin-film phosphors for patterned phosphor EL display applications, and broadband emission phosphors for the filtered white or color-by-white EL display approach. Focus is placed on the new EL materials and the composition modifications that have improved the performance of well-known EL materials.
LOCALIZED OPTICAL PHENOMENA AND THE CHARACTERIZATION OF MATERIALS INTERFACES
Authors: Bohn Paul W.
Published: July 2002

▪ Abstract  This review focuses on the characterization of interfaces, specifically on the optical methods of characterization that utilize some form of spatial localization to circumvent the special problems accruing to interfaces. Experiments utilizing radiation in only the infrared through the ultraviolet regions of the electromagnetic spectrum are considered. We specifically exclude the vast and important array of experimental techniques that utilize the vacuum ultraviolet and X-ray spectral regions. In addition, the interfaces considered are those composed of solids with liquids, thin films, and other solids, thus largely ignoring the literature of ultrahigh vacuum surface science.
IN SITU STUDIES OF THE PROPERTIES OF MATERIALS UNDER HIGH-PRESSURE AND TEMPERATURE CONDITIONS USING MULTI-ANVIL APPARATUS AND SYNCHROTRON X-RAYS
Authors: Parise J. B. , Weidner D. J. , Chen J. , Liebermann R. C. , Chen G.
Published: July 2002

▪ Abstract  Increased access to multi-anvil high-pressure devices interfaced to synchrotron X-ray radiation sources has led to a new class of experiments. These new capabilities include (a) high-precision crystal structure determination and refinement from powder X-ray diffraction data; (b) the determination of kinetic parameters and structure from time-resolved diffraction data; (c) the determination of absolute pressures by the combined use of ultrasonic techniques at high pressures and temperatures with simultaneous monitoring of X-ray diffraction; and (d) the determination of the strength and rheological properties of materials through the monitoring of the relaxation of broadened diffraction peak widths in the presence of a well-characterized deviatoric stress field generated in the multi-anvil high-pressure apparatus.
Phospholipid Strategies in Biomineralization and Biomaterials Research
Authors: Collier Joel H , Messersmith Phillip B
Published: July 2002

▪ Abstract  This review summarizes recent advances and future research trends in the field of phospholipid-based biomaterials. Lipids play an important role in biomineralization and countless other biological processes, and they are receiving increasing attention for the synthesis of new biomimetic biomaterials. Several emerging strategies in biomaterials research take advantage of phospholipids to compartmentalize and/or template chemical reactions via self-assembled structures such as liposomes and tubules. Still others exploit the inherent biocompatibility of phospholipids and phospholipid-mimetic materials for use as novel tissue-contacting biomaterials that mimic biological membranes. In the future, phospholipid-based materials may be increasingly utilized as tools for the manipulation of cell and tissue responses to biomaterials, for controlled drug release, for reconstructive surgery, and as tissue-engineered constructs.
Coagulase-Negative Staphylococci: Role as Pathogens
Authors: Huebner, MD Johannes , Goldmann, MD Donald A.
Published: July 2002

Coagulase-negative staphylococci have long been regarded as apathogenic but their important role as pathogens and their increasing incidence have been recognized and studied in recent years. Although specific virulence factors are not as clearly established as they are in Staphylococcus aureus, it seems clear that factors such as bacterial polysaccharide components are involved in attachment and/or persistence of bacteria on foreign materials. Coagulase-negative staphylococci are by far the most common cause of bacteremia related to indwelling devices. Most of these infections are hospital-acquired, and studies over the past several years suggest that they are often caused by strains that are transmitted among hospitalized patients. Other important infections due to coagulase-negative staphylococci include central nervous system shunt infections, native or prosthetic valve endocarditis, urinary tract infections, and endophthalmitis. Intravenous treatment of systemic infections is usually required because coagulase-negative staphylococci have become increasingly resistant to multiple antibiotics.
Role of Cytokines in the Pathogenesis of Inflammatory Bowel Disease
Authors: Papadakis Konstantinos A. , Targan Stephan R.
Published: July 2002

Recent advances in the drug treatment of inflammatory bowel disease (IBD) have paralleled our understanding of the pathophysiology of ulcerative colitis and Crohn’s disease. Several proinflammatory and immune-regulatory cytokines are upregulated in the mucosa of patients with IBD, and differences and similarities in the cytokine profiles of ulcerative colitis and Crohn’s disease have been elucidated. Several clinical trials involving a chimeric anti-TNF-α (tumor necrosis factor-α) antibody have shown marked clinical benefit in the majority of patients with Crohn’s disease, verifying the importance of TNF-α in the pathogenesis of Crohn’s disease. In preliminary studies, treatment with recombinant human interleukin-10 has been beneficial in Crohn’s disease but not in ulcerative colitis. Future treatment of IBD may include combination or sequential cytokine and anticytokine administration in defined groups of patients based on their mucosal cytokine profiles.
New Therapeutics for Chronic Heart Failure
Authors: Mann Douglas L. , Deswal Anita , Bozkurt Biykem , Torre-Amione Guillermo
Published: July 2002

▪ Abstract  Traditionally, clinicians have viewed heart failure either as a problem of excessive salt and water retention caused by abnormalities of renal blood flow, or as a hemodynamic problem associated with a reduced cardiac output and excessive peripheral vasoconstriction. Recently, clinicians have begun to adopt a neurohormonal model in which heart failure progresses because of the toxic effects of endogenous biological systems that become activated in heart failure. We review the rationale for existing heart failure therapies and discuss the reasoning behind the development of some emerging therapies.