ALBERT

Notes: Abstract Precise regulation of major histocompatibility complex class II (MHC-II) gene expression plays a crucial role in the control of the immune response. A major breakthrough in the elucidation of the molecular mechanisms involved in MHC-II regulation has recently come from the study of patients that suffer from a primary immunodeficiency resulting from regulatory defects in MHC-II expression. A genetic complementation cloning approach has led to the isolation of CIITA and RFX5, two essential MHC-II gene transactivators. CIITA and RFX5 are mutated in these patients, and the wild-type genes are capable of correcting their defect in MHC-II expression. The identification of these regulatory factors has furthered our understanding of the molecular mechanisms that regulate MHC-II genes. CIITA was found to be a non-DNA binding transactivator that functions as a molecular switch controlling both constitutive and inducible MHC-II expression. The finding that RFX5 is a subunit of the nuclear RFX-complex has confirmed that a deficiency in the binding of this complex is indeed the molecular basis for MHC-II deficiency in the majority of patients. Furthermore, the study of RFX has demonstrated that MHC-II promoter activity is dependent on the binding of higher-order complexes that are formed by highly specific cooperative binding interactions between certain MHC-II promoter-binding proteins. Two of these proteins belong to families of which the other members, although capable of binding to the same DNA motifs, are probably not directly involved in the control of MHC-II expression. Finally, the facts that CIITA and RFX5 are both essential and highly specific for MHC-II genes make possible novel strategies designed to achieve immunomodulation via transcriptional intervention.

Notes: Abstract Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNFalpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGFbeta and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNFalpha and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNFalpha was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNFalpha was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNFalpha at its apex. This led to the hypothesis that TNFalpha was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been successfully tested in animal models, of, for example, collagen-induced arthritis, and these studies have provided the rationale for clinical trials of anti-TNFalpha therapy in patients with long-standing rheumatoid arthritis. Several clinical trials using a chimeric anti-TNFalpha antibody have shown marked clinical benefit, verifying the hypothesis that TNFalpha is of major importance in rheumatoid arthritis. Retreatment studies have also shown benefit in repeated relapses, indicating that the disease remains TNFalpha dependent. Overall these studies demonstrate that analysis of cytokine expression and regulation may yield effective therapeutic targets in inflammatory disease.

Notes: Abstract In contrast with the study of alphabeta T cells, that of gammadelta T cells is relatively recent and stems from the discovery of their rearranged genes, rather than from any knowledge of their biological function. Thus, experiments designed to characterize their specificity and function have drawn heavily on our knowledge of alphabeta T cells. During the past few years, many studies, especially with mice lacking either alphabeta or gammadelta T cells, have demonstrated that gammadelta T cells can contribute to immune competence, but they do so in a way that is distinct from alphabeta T cells. It is also evident that gammadelta T cells may not recognize antigen the same way as do alphabeta T cells. Analysis of three protein antigens-the murine MHC class II IEk, the nonclassical MHC T10/T22, and the Herpes virus glycoprotein gI-indicates that gammadelta T cell recognition does not require antigen processing and that the proteins are recognized directly. In all three cases, recognition by these T cell clones involves neither peptides bound to these proteins nor peptides derived from them. Moreover, a group of small phosphate-containing nonpeptide compounds derived from mycobacterial extracts has been found to stimulate a major population of human peripheral gammadelta T cells in a T cell receptor (TCR)-dependent manner. This indicates that gammadelta T cells can respond to ligands that are different from those of alphabeta T cells. Analysis of complementarity determining region (CDR3) length distributions of gamma and delta chains indicates that they are more similar to those of immunoglobulins than to TCR alpha and beta. This further supports the idea that gammadelta and alphabeta T cells recognize antigens differently and suggests that gammadelta T cells may be more like immunoglobulins in their recognition properties. gammadelta T cells share many cell surface proteins with alphabeta T cells and are able to secrete lymphokines and express cytolytic activities in response to antigenic stimulation. These, together with the results cited above, indicate that gammadelta T cells can mediate cellular immune functions without a requirement for antigen processing. Thus, pathogens, damaged tissues, or even B and T cells can be recognized directly, and cellular immune responses can be initiated without a requirement for antigen degradation or specialized antigen-presenting cells. This would give gammadelta T cells greater flexibility than the more classical type of alphabeta T cell-mediated cellular immunity.

Notes: Abstract The transcription factor NF-kappaB has attracted widespread attention among researchers in many fields based on the following: its unusual and rapid regulation, the wide range of genes that it controls, its central role in immunological processes, the complexity of its subunits, and its apparent involvement in several diseases. A primary level of control for NF-kappaB is through interactions with an inhibitor protein called IkappaB. Recent evidence confirms the existence of multiple forms of IkappaB that appear to regulate NF-kappaB by distinct mechanisms. NF-kappaB can be activated by exposure of cells to LPS or inflammatory cytokines such as TNF or IL-1, viral infection or expression of certain viral gene products, UV irradiation, B or T cell activation, and by other physiological and nonphysiological stimuli. Activation of NF-kappaB to move into the nucleus is controlled by the targeted phosphorylation and subsequent degradation of IkappaB. Exciting new research has elaborated several important and unexpected findings that explain mechanisms involved in the activation of NF-kappaB. In the nucleus, NF-kappaB dimers bind to target DNA elements and activate transcription of genes encoding proteins involved with immune or inflammation responses and with cell growth control. Recent data provide evidence that NF-kappaB is constitutively active in several cell types, potentially playing unexpected roles in regulation of gene expression. In addition to advances in describing the mechanisms of NF-kappaB activation, excitement in NF-kappaB research has been generated by the first report of a crystal structure for one form of NF-kappaB, the first gene knockout studies for different forms of NF-kappaB and of IkappaB, and the implications for therapies of diseases thought to involve the inappropriate activation of NF-kappaB.

Notes: Abstract The use of immunotoxins (ITs) in the therapy of cancer, graft-vs-host disease (GvHD), autoimmune diseases, and AIDS has been ongoing for the past two decades. ITs contain a targeting moiety for delivery and a toxic moiety for cytotoxicity. Theoretically, one molecule of a toxin, routed to the appropriate cellular compartment, will be lethal to a cell. Newly developed MoAbs, toxins, and molecular biological technologies have enabled researchers to construct ITs that can effectively kill many different cell types. In fact, phase I/II clinical trials have given promising results. Although nonspecific toxicity and immunogenicity still limit the use of IT therapy, these agents hold enormous promise in an optimal setting to treat minimal disease.

Notes: Abstract B lymphopoiesis is regulated by multiple signals from stromal cell contact, soluble cytokines, antigen, and T helper cells. In vitro and biochemical experiments have implicated tyrosine kinases as key components of many of these signaling pathways. Genetic analysis of the role of these tyrosine kinases has been facilitated by recent advances in transgenic and gene targeting technology as well as by the identification of the genetic basis of several human and murine immune deficiencies. This review discusses the effect of gain and loss of function mutations of selected tyrosine kinases and their regulators and substrates on B cell development and function.

Notes: Abstract T cells play a central role in the initiation and regulation of the immune response to antigen. Both the engagement of the TCR with MHC/Ag and a second signal are needed for the complete activation of the T cell. The CD28/B7 receptor/ligand system is one of the dominant costimulatory pathways. Interruption of this signaling pathway with CD28 antagonists not only results in the suppression of the immune response, but in some cases induces antigen-specific tolerance. However, the CD28/B7 system is increasingly complex due to the identification of multiple receptors and ligands with positive and negative signaling activities. This review summarizes the state of CD28/B7 immunobiology both in vitro and in vivo; summarizes the many experiments that have led to our current understanding of the participants in this complex receptor/ligand system; and illustrates the current models for CD28/B7-mediated T cell and B cell regulation. It is our hope and expectation that this review will provoke additional research that will unravel this important, yet complex, signaling pathway.

Notes: Abstract 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.

Notes: Abstract A taxonomically diverse group of bacterial pathogens have evolved a variety of strategies to subvert host-cellular functions to their advantage. This often involves two-way biochemical interactions leading to responses in both the pathogen and host cell. Central to this interaction is the function of a specialized protein secretion system that directs the export and/or translocation into the host cells of a number of bacterial proteins that can induce or interfere with host-cell signal transduction pathways. The understanding of these bacterial/host-cell interactions will not only lead to novel therapeutic approaches but will also result in a better understanding of a variety of basic aspects of cell physiology and immunology.

Notes: Abstract More than 100 years have passed since Weismann first recognized the role of germ cells in the continuity of a species. Today, it remains unclear how a germ cell is initially set aside from somatic cells and how it chooses its unique developmental path. In this review, we address various aspects of germ cell development in Drosophila, such as germ cell determination, germ cell migration, gonad formation, sex determination, and gametogenesis. Many aspects of germ cell development, including the morphology of germ cells, their migratory behavior, as well as the processes of gonad formation and gametogenesis, show striking similarities among organisms. Considering the conservation of factors that regulate somatic development, it is likely that some aspects of germ cell development are shared not only on a morphological but also on the molecular level between Drosophila and other organisms.

Notes: Abstract The Toll-Dorsal pathway in Drosophila and the interleukin-1 receptor (IL-1R)-NF-kappaB pathway in mammals are homologous signal transduction pathways that mediate several different biological responses. In Drosophila, genetic analysis of dorsal-ventral patterning of the embryo has defined the series of genes that mediate the Toll-Dorsal pathway. Binding of extracellular ligand activates the transmembrane receptor Toll, which requires the novel protein Tube to activate the cytoplasmic serine/threonine kinase Pelle. Pelle activity controls the degradation of the Cactus protein, which is present in a cytoplasmic complex with the Dorsal protein. Once Cactus is degraded in response to signal, Dorsal is free to move into the nucleus where it regulates transcription of specific target genes. The Toll, tube, pelle, cactus, and dorsal genes also appear to be involved in Drosophila immune response. Because the IL-1R-NF-kappaB pathway plays a role in vertebrate innate immunity and because plant homologues of the Toll-Dorsal pathway are important in plant disease resistance, it is likely that this pathway arose before the divergence of plants and animals as a defense against pathogens.

Notes: Abstract ATP and other nucleotides can be released from cells through regulated pathways, or following the loss of plasma membrane integrity. Once outside the cell, these compounds take on new roles as intercellular signaling molecules that elicit a broad spectrum of physiological responses through the activation of numerous cell surface receptor subtypes. This review summarizes recent advances in the molecular characterization of ATP receptors and discusses roles for cloned receptors in established and novel physiological processes.

Notes: Abstract Motor proteins perform a wide variety of functions in all eukaryotic cells. Recent advances in the structural and mutagenic analysis of the myosin motor has led to insights into how these motors transduce chemical energy into mechanical work. This review focuses on the analysis of the effects of myosin mutations from a variety of organisms on the in vivo and in vitro properties of this ubiquitous motor and illustrates the positions of these mutations on the high-resolution three-dimensional structure of the myosin motor domain.

Notes: Abstract A violent outflow of high-velocity gas is one of the first manifestations of the formation of a new star. Such outflows emerge bipolarly from the young object and involve amounts of energy similar to those involved in accretion processes. The youngest (proto-)stellar low-mass objects known to date (the Class 0 protostars) present a particularly efficient outflow activity, indicating that outflow and infall motions happen simultaneously and are closely linked since the very first stages of the star formation processes. This article reviews the wealth of information being provided by large millimeter-wave telescopes and interferometers on the small-scale structure of molecular outflows, as well as the most recent theories about their origin. The observations of highly collimated CO outflows, extremely high velocity (EHV) flows, and molecular "bullets" are examined in detail, since they provide key information on the origin and propagation of outflows. The peculiar chemistry operating in the associated shocked molecular regions is discussed, highlighting the recent high-sensitivity observations of low-luminosity sources. The classification schemes and the properties of the driving sources of bipolar outflows are summarized with special attention devoted to the recently identified Class 0 protostars. All these issues are crucial for building a unified theory on the mass-loss phenomena in young stars.

Notes: Abstract We discuss current observational and theoretical knowledge of magnetic fields, especially the large-scale structure in the disks and halos of spiral galaxies. Among other topics, we consider the enhancement of global magnetic fields in the interarm regions, magnetic spiral arms, and representations as superpositions of azimuthal modes, emphasizing a number of unresolved questions. It is argued that a turbulent hydromagnetic dynamo of some kind and an inverse cascade of magnetic energy gives the most plausible explanation for the regular galactic magnetic fields. Primordial theory is found to be unsatisfactory, and fields of cosmological origin may not even be able to provide a seed field for a dynamo. Although dynamo theory has its own problems, the general form of the dynamo equations appears quite robust. Finally, detailed models of magnetic field generation in galaxies, allowing for factors such as spiral structure, starbursts, galactic winds, and fountains, are discussed and confronted with observations.

Notes: Abstract The cooling flows or winds from evolved stars are ideal for the formation of molecules and dust. The main location of molecular synthesis is the outer circumstellar envelope, where UV radiation from the interstellar medium penetrates the envelope and, by photodissociating parent molecules, produces the high-energy radicals and ions that activate gas-phase neutral and ion-molecule chemistry. After introducing relevant observational results and theoretical ideas, the salient aspects of the photochemical model are described. The primary application is to the nearby C star, IRC + 10216, where 50 or more circumstellar molecules have been detected. Recent interferometer maps, with resolution approaching 1'', provide the means to verify the main ideas of the model and to indicate directions for its improvement.

Notes: Abstract The central half kiloparsec region of our Galaxy harbors a variety of phenomena unique to the central environment. This review discusses the observed structure and activity of the interstellar medium in this region in terms of its inevitable inflow toward the center of the Galactic gravitational potential well. A number of dissipative processes lead to a strong concentration of gas into a "Central Molecular Zone" of about 200-pc radius, in which the molecular medium is characterized by large densities, large velocity dispersions, high temperatures, and apparently strong magnetic fields. The physical state of the gas and the resultant star formation processes occurring in this environment are therefore quite unlike those occurring in the large-scale disk. Gas not consumed by star formation either enters a hot X ray-emitting halo and is lost as a thermally driven galactic wind or continues moving inward, probably discontinuously, through the domain of the few parsec-sized circumnuclear disks and eventually into the central parsec. There, the central radio source SgrA* currently accepts only a tiny fraction of the inflowing material, likely as a result of a limit cycle wherein the continual inflow of matter provokes star formation, which in turn can temporarily halt the inflow via mass-outflow winds.

Notes: Abstract At luminosities above 1011 , infrared galaxies become the dominant population of extragalactic objects in the local Universe (z〈 0.3), being more numerous than optically selected starburst and Seyfert galaxies and quasi-stellar objects at comparable bolometric luminosity. The trigger for the intense infrared emission appears to be the strong interaction/merger of molecular gas-rich spirals, and the bulk of the infrared luminosity for all but the most luminous objects is due to dust heating from an intense starburst within giant molecular clouds. At the highest luminosities (Lir〉 1012 ), nearly all objects appear to be advanced mergers powered by a mixture of circumnuclear starburst and active galactic nucleus energy sources, both of which are fueled by an enormous concentration of molecular gas that has been funneled into the merger nucleus. These ultraluminous infrared galaxies may represent an important stage in the formation of quasi-stellar objects and powerful radio galaxies. They may also represent a primary stage in the formation of elliptical galaxy cores, the formation of globular clusters, and the metal enrichment of the intergalactic medium.

Notes: Abstract We review the strategy used to identify a susceptibility locus (IDDM2) for type 1 (insulin dependent) diabetes mellitus. As type 1 diabetes is becoming the paradigm for dissecting multifactorial disease genetics, the approach described provides important general guidelines for positional cloning of human disease polygenes. Main topics include: (a) historical conspectus of the mapping and identification of IDDM2-a critical survey of the work leading up to the conclusion that IDDM2 most likely corresponds to allelic variation at the insulin gene minisatellite (VNTR) locus; (b) the nature of allelic (length and sequence) variation at the VNTR locus; (c) gene interactions and disease pathogenesis; (d) mechanism of action of the INS VNTR in type 1 diabetes-insulin gene expression, parent-of-origin effects (genomic imprinting); and (e) summary and future prospects-alleles of the insulin VNTR that are protective for type 1 diabetes appear to encode susceptibility to type 2 diabetes.

Notes: It is not generally realized that genetics has finally solved the age-old problem of the reason for the existence (i.e. the function) of sexuality and sex, and that only geneticists can properly answer the question, "Is sex necessary?" Optimality arguments and modifier theory are reviewed as paradigms for the study of the evolution of recombination. Optimality criteria (such as maximization of mean fitness) may agree with results from models developed in terms of the evolution of recombination at modifier loci. Modifier models demonstrate, however, that equilibrium mean fitness can decrease during the evolution of recombination rates and is not always maximized. Therefore, optimality arguments do not successfully predict the conditions under which increased or decreased recombination will evolve. The results from modifier models indicate that decreased recombination rates are usually favored when the population is initially near a polymorphic equilibrium with linkage disequilibrium. When the population is subject to directional selection or to deleterious mutations, increased recombination may be favored under certain conditions, provided that there is negative epistasis among alleles.

Notes: Abstract The past few years have seen a wider acceptance of a role for DNA methylation in cancer. This can be attributed to three developments. First, the documentation of the over-representation of mutations at CpG dinucleotides has convincingly implicated DNA methylation in the generation of oncogenic point mutations. The second important advance has been the demonstration of epigenetic silencing of tumor suppressor genes by DNA methylation. The third development has been the utilization of experimental methods to manipulate DNA methylation levels. These studies demonstrate that DNA methylation changes in cancer cells are not mere by-products of malignant transformation, but can play an instrumental role in the cancer process. It seems clear that DNA methylation plays a variety of roles in different cancer types and probably at different stages of oncogenesis. DNA methylation is intricately involved in a wide diversity of cellular processes. Likewise, it appears to exert its influence on the cancer process through a diverse array of mechanisms. It is our task not only to identify these mechanisms, but to determine their relative importance for each stage and type of cancer. Our hope then will be to translate that knowledge into clinical applications.

Notes: Abstract The Hox homeobox gene family plays a pivotal role in regulating patterning and axial morphogenesis in vertebrates. Molecular characterization of the four Hox clusters has shown that they are evolutionarily related with respect to sequence, organization, and expression, suggesting they arose by duplication and divergence. Transgenic analysis has clearly demonstrated the functional roles of individual genes in a broad range of embryonic tissues, and in compound mutants has addressed the issues of cooperativity and redundancy. There is an emerging picture of the cis-regulatory elements underlying Hox expression, and for the 3' members of the clusters there is a considerable degree of conservation between paralogous genes with respect to their functional roles and regulatory control.

Notes: Abstract The ciliated protozoa divide the labor of germline and somatic genetic functions between two distinct nuclei. The development of the somatic (macro-) nucleus from the germinal (micro-) nucleus occurs during sexual reproduction and involves large-scale, genetic reorganization including site-specific chromosome breakage and DNA deletion. This intriguing process has been extensively studied in Tetrahymena thermophila. Characterization of cis-acting sequences, putative protein factors, and possible reaction intermediates has begun to shed light on the underlying mechanisms of genome rearrangement. This article summarizes the current understanding of this phenomenon and discusses its origin and biological function. We postulate that ciliate nuclear restructuring serves to segregate the two essential functions of chromosomes: the transmission and expression of genetic information.

Notes: Abstract Over the past several years, a number of human tumor suppressor genes have been cloned and characterized. Germline mutations in tumor suppressor genes strongly predispose to cancer, and they are also mutated somatically in sporadic forms of the disease. In order to create animal models for the familial cancer syndromes caused by inherited mutations in these genes as well as to determine their role in embryogenesis, the homologues of several members of this class have been mutated in the mouse. The initial characterization of the heterozygous and homozygous phenotypes caused by these mutations has led to important insights into the mechanisms by which tumor suppressor genes participate in normal development and how their loss contributes to tumorigenesis.

Notes: Abstract The aryl hydrocarbon (Ah) receptor has occupied the attention of toxicologists for over two decades. Interest arose from the early observation that this soluble protein played key roles in the adaptive metabolic response to polycyclic aromatic hydrocarbons and in the toxic mechanism of halogenated dioxins and dibenzofurans. More recent investigations have provided a fairly clear picture of the primary adaptive signaling pathway, from agonist binding to the transcriptional activation of genes involved in the metabolism of xenobiotics. Structure-activity studies have provided an understanding of the pharmacology of this receptor; recombinant DNA approaches have identified the enhancer sequences through which this factor regulates gene expression; and functional analysis of cloned cDNAs has allowed the characterization of the major signaling components in this pathway. Our objective is to review the Ah receptor's role in regulation of xenobiotic metabolism and use this model as a framework for understanding the less well-characterized mechanism of dioxin toxicity. In addition, it is hoped that this information can serve as a model for future efforts to understand an emerging superfamily of related signaling pathways that control biological responses to an array of environmental stimuli.

Notes: Abstract Receptors for the Fc domain of immunoglobulins play an important role in immune defense. There are two well-defined functional classes of mammalian receptors. One class of receptors transports immunoglobulins across epithelial tissues to their main sites of action. This class includes the neonatal Fc receptor (FcRn), which transports immunoglobulin G (IgG), and the polymeric immunoglobulin receptor (pIgR), which transports immunoglobulin A (IgA) and immunoglobulin M (IgM). Another class of receptors present on the surfaces of effector cells triggers various biological responses upon binding antibody-antigen complexes. Of these, the IgG receptors (FcgammaR) and immunoglobulin E (IgE) receptors (FcepsilonR) are the best characterized. The biological responses elicited include antibody-dependent, cell-mediated cytotoxicity, phagocytosis, release of inflammatory mediators, and regulation of lymphocyte proliferation and differentiation. We summarize the current knowledge of the structures and functions of FcRn, pIgR, and the FcgammaR and FcepsilonRI proteins, concentrating on the interactions of the extracellular portions of these receptors with immunoglobulins.

Notes: Abstract Peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors that belong to the steroid/thyroid/retinoic acid receptor superfamily. All their characterized target genes encode proteins that participate in lipid homeostasis. The recent finding that antidiabetic thiazolidinediones and adipogenic prostanoids are ligands of one of the PPARs reveals a novel signaling pathway that directly links these compounds to processes involved in glucose homeostasis and lipid metabolism including adipocyte differentiation. A detailed understanding of this pathway could designate PPARs as targets for the development of novel efficient treatments for several metabolic disorders.

Notes: Abstract Focal adhesions are sites of tight adhesion to the underlying extracellular matrix developed by cells in culture. They provide a structural link between the actin cytoskeleton and the extracellular matrix and are regions of signal transduction that relate to growth control. The assembly of focal adhesions is regulated by the GTP-binding protein Rho. Rho stimulates contractility which, in cells that are tightly adherent to the substrate, generates isometric tension. In turn, this leads to the bundling of actin filaments and the aggregation of integrins (extracellular matrix receptors) in the plane of the membrane. The aggregation of integrins activates the focal adhesion kinase and leads to the assembly of a multicomponent signaling complex.

Notes: Abstract Significant progress has been made in elucidating the mechanisms of viral membrane fusion proteins; both those that function at low, as well as those that function at neutral, pH. For many viral fusion proteins evidence now suggests that a triggered conformational change that exposes a previously cryptic fusion peptide, along with a rearrangement of the fusion protein oligomer, allows the fusion peptide to gain access to the target bilayer and thus initiate the fusion reaction. Although the topologically equivalent process of cell-cell fusion is less well understood, several cell surface proteins, including members of the newly described ADAM gene family, have emerged as candidate adhesion/fusion proteins.

Notes: Abstract In the past decade a number of observational and theoretical studies have appeared that address the problem of how both the physical conditions in subsurface layers of the Sun and the nature of the magnetic flux tubes of active regions are reflected in the structure and behavior of these regions at the surface. This review discusses work in this area. Many characteristics of plages and sunspot groups are shown to be related to the conditions encountered by the region flux tube as it rises through the convective zone of the Sun to the surface. Size distributions, rotation and meridional flow rates and their covariances, and characteristics of growth and decay are among the factors that have been shown to depend on the nature of the source magnetic flux tube and the physical effects, such as the Coriolis force and magnetic tension, that act deep in the convection zone.

Notes: Abstract A growing number of genetic systems have been shown to be controlled at the level of premature termination of transcription. Genes in this class contain transcription termination signals in the region upstream of the coding sequence. The activity of these regulatory termination signals is controlled through a variety of mechanisms. These include modification of RNA polymerase to a terminator-resistant, or terminator-prone form, and alterations in the structure of the nascent transcript, to determine whether the stem-loop structure of an intrinsic terminator or an alternate antiterminator is formed. Structural alterations in the transcript can be controlled by the kinetics of translation of the RNA, by binding of specific regulatory proteins, and by mRNA-tRNA interactions. This review describes a number of variations on the termination control theme that have been uncovered in prokaryotes.

Notes: Abstract Heterocysts are microaerobic, N2-fixing cells that form in a patterned array within O2-producing filamentous cyanobacteria. Structural features of heterocysts can be predicted from consideration of their physiology. This review focuses on the spacing mechanism that determines which cells will differentiate, and on the regulation of the progression of the differentiation process. Applicable genetic tools, developed primarily using Anabaena PCC 7120, but employed also with Nostoc spp., are reviewed. These tools include localization of transcription using fusions to lux, lac, and gfp, and mutagenesis with oriV-containing derivatives of transposon Tn5. Mature and developing heterocysts inhibit nearby vegetative cells from differentiating; genes patA, devA, hetC, and the hetMNI locus may hold keys to understanding intercellular interactions that influence heterocyst formation. Regulatory and other genes that are transcriptionally activated at different times after nitrogen stepdown have been identified, and should permit analysis of mechanisms that underlie the progression of heterocyst differentiation.

Notes: Abstract Type II DNA topoisomerases are essential and ubiquitous DNA metabolic enzymes that alter DNA topology. Eubacteria have two indispensable type II DNA topoisomerases, DNA gyrase encoded by gyrB and gyrA and topoisomerase IV encoded by parE and parC. These genes belong to a single family whose members span both eukaryotes and prokaryotes. The highly conserved motifs in these genes provide a rationale for the design of universal primers used in the polymerase chain reaction in order to systematically generate a data set suitable for bacterial diversity studies at the macro-diversity level, as well as at the micro-diversity level displaying individual species and isolates. This family of genes is the subject of intensive biochemical and genetic analyses, which provide an opportunity for comprehensive understanding of sequence conservation and variability and their relationship to function. These genes are ideally suited for microbial identification and biodiversity analyses.

Notes: Abstract Parental imprinting is a process that results in allele-specific differences in transcription, DNA methylation, and DNA replication timing. Imprinting plays an important role in development, and its deregulation can cause certain defined disease states. Absence of a paternal contribution to chromosome 15q11-q13, due to hemizygous deletion or uniparental disomy, results in the Prader-Willi syndrome. The absence of a normal maternal copy of the same region causes Angelman syndrome. The Beckwith-Wiedemann syndrome is associated with the failure of normal biparental inheritance of chromosome 11p15, and loss of imprinting is observed in several cancers including Wilms' tumor. The study of the molecular basis of abnormal imprinting in these disorders will facilitate the identification and characterization of other imprinted human disease loci.

Notes: Abstract A combination of classical genetic, biochemical, and molecular biological approaches have generated a rather detailed understanding of the structure and function of Saccharomyces telomeres. Yeast telomeres are essential to allow the cell to distinguish intact from broken chromosomes, to protect the end of the chromosome from degradation, and to facilitate the replication of the very end of the chromosome. In addition, yeast telomeres are a specialized site for gene expression in that the transcription of genes placed near them is reversibly repressed. A surprisingly large number of genes have been identified that influence either telomere structure or telomere function (or both), although in many cases the mechanism of action of these genes is poorly understood. This article reviews the recent literature on telomere biology and highlights areas for future research.

Notes: Abstract Much of our understanding of the molecular basis of mitotic spindle function has been achieved within the past decade. Studies utilizing genetically tractable organisms have made important contributions to this field and these studies form the basis of this review. We focus upon three areas of spindle research: spindle poles, centromeres, and spindle motors. The structure and duplication mechanisms of spindle poles are considered as well as their roles in organizing spindle microtubules. Centromeres vary considerably in their size and complexity. We describe recent progress in our understanding of the relatively simple centromeres of the yeast Saccharomyces cerevisiae and the complex centromeres that are more typical of eukaryotic cells. Microtubule-based motor proteins that generate the characteristic spindle movements have been identified in recent years and can be grouped into families defined by conserved primary sequence and mitotic function.

Notes: Abstract Specialized cytoskeletons play many fascinating roles, including mechanical integrity and wound-healing in epidermal cells, cell polarity in simple epithelia, contraction in muscle cells, hearing and balance in the inner ear cells, axonal transport in neurons, and neuromuscular junction formation between muscle cells and motor neurons. These varied functions are dependent upon cytoplasmic networks of actin microfilaments (6 nm), intermediate filaments (10 nm) and microtubules (23 nm), and their many associated proteins. In this chapter, I review what is known about the cytoskeletons of intermediate filaments and their associated proteins. I focus largely on epidermal cells, which devote most of their protein-synthesizing machinery to producing an extensive intermediate filament network composed of keratin. Recent studies have shown that many of the devastating human disorders that arise from degeneration of this cell type have as their underlying basis either defects in the genes encoding keratins or abnormalities in keratin IF networks. I discuss what we know about the functions of IFs, and how the link to genetic disease has enhanced this understanding.

Notes: Abstract Marsupials and monotremes, the mammals most distantly related to placental mammals, share essentially the same genome but show major variations in chromosome organization and function. Rules established for the mammalian genome by studies of human and mouse do not always apply to these distantly related mammals, and we must make new and more general laws. Some examples are contradictions to our assumption of frequent genome reshuffling in vertebrate evolution, Ohno's Law of X chromosome conservation, the Lyon Hypothesis of X chromosome inactivation, sex chromosome pairing, several explanations of Haldane's Rule, and the theory that the mammalian Y chromosome contains a male-specific gene with a direct dominant action on sex determination. Significantly, it is not always the marsupials and monotremes (usually considered the weird mammals) that are exceptional. In many features, it appears that humans and, particularly, mice are the weird mammals that break more general mammalian, or even vertebrate rules.

Notes: 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.

Notes: Abstract Recent studies on the development of the legs and wings of Drosophila have led to the conclusion that insect limb development is controlled by localized pattern organizing centers, analogous to those identified in vertebrate embryos. Genetic analysis has defined the events that lead to the formation of these organizing centers and has led to the identification of gene products that mediate organizer function. The possibility of homology between vertebrate and insect limbs is considered in light of recently reported similarities in patterns of gene expression and function.

Notes: Abstract In this chapter, we review the structure and composition of interphase and mitotic chromosomes. We discuss how these observations support the model that mitotic condensation is a deterministic process leading to the invariant folding of a given chromosome. The structural studies have also placed constraints on the mechanism of condensation and defined several activities needed to mediate condensation. In the context of these activities and structural information, we present our current understanding of the role of cis sites, histones, topoisomerase II, and SMC proteins in condensation. We conclude by using our current knowledge of mitotic condensation to address the differences in chromosome condensation observed from bacteria to humans and to explore the relevance of this process to other processes such as gene expression.

Notes: Abstract Proteins that function in transport vesicle docking are being identified at a rapid rate. So-called v- and t-SNAREs form the core of a vesicle docking complex. Additional accessory proteins are required to protect SNAREs from promiscuous binding and to deprotect SNAREs under conditions in which transport vesicle docking should occur. Because access to SNAREs must be regulated, other proteins must also contain specificity determinants to accomplish delivery of transport vesicles to their distinct and specific membrane targets.

Notes: Abstract Karyogamy, or nuclear fusion, is the process during mating by which two haploid yeast nuclei fuse to produce a single diploid nucleus. Karyogamy occurs in two major steps: microtubule-dependent nuclear congression followed by fusion of the nuclear envelope membranes. Many of the proteins required for karyogamy have been discovered to act in related processes during mitotic growth. Accordingly, yeast karyogamy has become an important model system to investigate critical functions of the cytoplasmic microtubules and the microtubule organizing center, the nuclear envelope, and the endoplasmic reticulum.

Notes: Abstract Endocytosis in eukaryotic cells is characterized by the continuous and regulated formation of prolific numbers of membrane vesicles at the plasma membrane. These vesicles come in several different varieties, ranging from the actin-dependent formation of phagosomes involved in particle uptake, to smaller clathrin-coated vesicles responsible for the internalization of extracellular fluid and receptor-bound ligands. In general, each of these vesicle types results in the delivery of their contents to lysosomes for degradation. The membrane components of endocytic vesicles, on the other hand, are subject to a series of highly complex and iterative molecular sorting events resulting in their targeting to specific destinations. In recent years, much has been learned about the function of the endocytic pathway and the mechanisms responsible for the molecular sorting of proteins and lipids. This review attempts to integrate these new concepts with long-established views of endocytosis to present a more coherent picture of how the endocytic pathway is organized and how the intracellular transport of internalized membrane components is controlled. Of particular importance are emerging concepts concerning the protein-based signals responsible for molecular sorting and the cytosolic complexes responsible for the decoding of these signals.

Notes: Abstract Proteins that contain the Arg-Gly-Asp (RGD) attachment site, together with the integrins that serve as receptors for them, constitute a major recognition system for cell adhesion. The RGD sequence is the cell attachment site of a large number of adhesive extracellular matrix, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands. Some other integrins bind to related sequences in their ligands. The integrin-binding activity of adhesion proteins can be reproduced by short synthetic peptides containing the RGD sequence. Such peptides promote cell adhesion when insolubilized onto a surface, and inhibit it when presented to cells in solution. Reagents that bind selectively to only one or a few of the RGD-directed integrins can be designed by cyclizing peptides with selected sequences around the RGD and by synthesizing RGD mimics. As the integrin-mediated cell attachment influences and regulates cell migration, growth, differentiation, and apoptosis, the RGD peptides and mimics can be used to probe integrin functions in various biological systems. Drug design based on the RGD structure may provide new treatments for diseases such as thrombosis, osteoporosis, and cancer.

Notes: Abstract In most space environments, dust particles are exposed to plasmas and UV radiation and, consequently, carry electrostatic charges. Their motion is influenced by electric and magnetic fields in addition to gravity, drag, and radiation pressure. On the surface of the Moon, in planetary rings, or at comets, for example, electromagnetic forces can shape the spatial and size distribution of micron-sized charged dust particles. The dynamics of small charged dust particles can be surprisingly complex, leading to levitation, rapid transport, energization and ejection, capture, and the formation of new planetary rings. This review briefly discusses the most important processes that determine the charge state of dust particles immersed in plasmas and the resulting dynamics on exposed dusty surfaces and in planetary magnetospheres.

Notes: Abstract The status of searches for gravitational microlensing events of the stars in our galaxy and in other galaxies of the Local Group, the interpretation of the results, some theory, and prospects for the future are reviewed. The searches have already unveiled ~ 100 events, at least two of them caused by binaries, and have already proven to be useful for studies of the Galactic structure. The events detected so far are probably attributable to the effects of ordinary stars, and possibly to substellar brown dwarfs; however, a firm conclusion cannot be reached yet because the analysis published to date is based on a total of only 16 events. The current searches, soon to be upgraded, will probably allow determination of the mass function of stars and brown dwarfs in the next few years; these efforts will also provide good statistical information about binary systems, in particular their mass ratios. They may also reveal the nature of dark matter and allow us to detect planets and planetary mass objects.

Notes: Abstract A careful assessment of current uncertainties in stellar physics (opacities, nuclear reaction rates, equation of state effects, diffusion, rotation, and mass loss), in the chemistry of globular cluster (GC) stars, and in the cluster distance scale, suggests that the most metal-poor (presumably the oldest) of the Galaxy's GCs have ages near 15 Gyr. Ages below 12 Gyr or above 20 Gyr appear to be highly unlikely. If these = 2 sigma limits are increased by ~ 1 Gyr to account for the formation time of the globulars, and if standard Friedmann cosmologies with the cosmological constant set to zero are assumed, then the GC constraint on the present age of the Universe (t0〉= 13 Gyr) implies that the Hubble constant H0〈= 51 km s-1 Mpc-1 if the density parameter Omega = 1 or 〈= 62 km s-1 Mpc-1 if Omega = 0.3.

Notes: Abstract Stars over essentially the whole mass domain can become pulsationally unstable during various stages of their evolution. They will appear as variable stars with characteristics that are of much diagnostic value to astronomers. The analysis of such observations provides a challenging and unique approach to study aspects of the internal constitution and evolutionary status of these objects that are not accessible otherwise. This review touches on most classes of known pulsating variable stars and tries to elucidate connections to stellar physical aspects. To aid future investigations, we stress questions and problems that we believe are yet to be resolved satisfactorily.

Notes: Abstract The Magellanic Clouds have galactocentric distances of 50 and 63 kiloparsecs, making it possible to probe the older populations of clusters and stars in some detail. Although it is clear that both galaxies contain an old population, it is not yet certain whether this population is coeval with the date of formation of the oldest globulars in the Milky Way. The kinematics of this old population in the Large Magellanic Cloud (LMC) are surprising; no component of this old population is currently measured to be part of a hot halo supported by velocity dispersion. Spectroscopy of field stars is beginning to show the existence of a small population of stars with abundances [Fe/H] less than -1.4. These stars will help to unravel the star-formation history when the next generation of telescopes are commissioned. Asymptotic giant branch stars, long-period variables, planetary nebulae, and horizontal-branch clump stars can be used to trace the extent and kinematics of the intermediate-age population. Deep color-magnitude diagrams can be used to derive the relative proportions of stars older than 1 Gyr. The age distribution of populous clusters and the age-metallicity relation are used to compare the evolution of the two Magellanic Clouds to each other. The issue of where the LMC's metals originated is explored, as is the question of what triggers star formation in the Clouds.

Notes: Abstract A growing number of cellular regulatory mechanisms are being linked to protein modification by the polypeptide ubiquitin. These include key transitions in the cell cycle, class I antigen processing, signal transduction pathways, and receptor-mediated endocytosis. In most, but not all, of these examples, ubiquitination of a protein leads to its degradation by the 26S proteasome. Following attachment of ubiquitin to a substrate and binding of the ubiquitinated protein to the proteasome, the bound substrate must be unfolded (and eventually deubiquitinated) and translocated through a narrow set of channels that leads to the proteasome interior, where the polypeptide is cleaved into short peptides. Protein ubiquitination and deubiquitination are both mediated by large enzyme families, and the proteasome itself comprises a family of related but functionally distinct particles. This diversity underlies both the high substrate specificity of the ubiquitin system and the variety of regulatory mechanisms that it serves.

Notes: Abstract Archaeologists are in the midst of restructuring their relationship with Native Americans. The legal, political, social, and intellectual ramifications of this process are reviewed to examine the fundamental changes occurring in the way archaeology is conducted in the Americas. Much of the impetus for this change resulted from the criticism of archaeology by Native Americans, which led to passage of the Native American Graves Protection and Repatriation Act of 1990 (NAGPRA). NAGPRA has indelibly changed how archaeologists will work in the United States. The issues raised by Native Americans about why and how archaeological research is conducted, however, go beyond NAGPRA to the paradigmatic basis of archaeology. Archaeologists will have new opportunities available to them if they work in partnership with Native Americans in studying the rich archaeological record in the Americas.

Notes: Abstract The household has emerged as a focus of archaeological inquiry over the past decade. This review summarizes issues raised by economic and feminist anthropologists about the meaning of the terms household and domestic and then considers research on household archaeology, craft specialization, and gender relevant to the study of the organization of domestic labor. It is argued that the common functional definition of the household as an adaptive mechanism reacting to environmental and social conditions underconceptualizes the household and renders its study unlikely to contribute to our understanding of economic and social processes in past societies. Studies of craft specialization and women's economic production that emphasize what members of the domestic group do and how that action is valued are more successful in demonstrating the dynamic interaction between household and society.

Notes: Abstract This review contrasts the relative lack of interest in "popular culture" within anthropology with the close, increasingly critical attention this concept has received within cultural studies. Rejecting both a production-oriented model of a manipulative mass culture imposed from above and a reception-oriented model of an expressive culture of the people, cultural studies scholars broke with essentialized conceptions and redefined the popular in Gramscian terms, as a zone of contestation, a site where the struggle for hegemony unfolds. The review uses this approach to relate the production of popular culture to class formation in the United States. Against overemphasis on the ideological effectivity of popular culture and a revisionist tendency to redefine it in affirmative, politically essentialized terms, the review suggests that contradictions and instabilities characterize all stages of the popular cultural circuit: commodity, text, and lived culture.

Notes: Abstract Recent perspectives in anthropological research define a disaster as a process/event involving the combination of a potentially destructive agent(s) from the natural and/or technological environment and a population in a socially and technologically produced condition of vulnerability. From this basic understanding three general topical areas have developed: (a) a behavioral and organizational response approach, (b) a social change approach, and (c) a political economic/environmental approach, focusing on the historical-structural dimensions of vulnerability to hazards, particularly in the developing world. Applied anthropological contributions to disaster management are discussed as well as research on perception and assessment of hazard risk. The article closes with a discussion of potentials in hazard and disaster research for theory building in anthropology, particularly in issues of human-environment relations and sociocultural change.

Notes: In this professional memoir I trace my career and the changes that occurred after World War II in the biological anthropology studies of human populations. I describe my academic training at the University of New Mexico and Harvard University and my research training at the US Climatic Research Laboratory. During my academic career at The Pennsylvania State University, I directed two multidisciplinary research efforts as part of the International Biological Programme and Man in the Biosphere Program. These were the high-altitude studies in Nunoa, Peru, and the migration and modernization studies of Samoan communities. I describe my participation in the development of these international science programs as well as the effects on the discipline of biological anthropology. In conclusion, I reflect on the growth and development of biological anthropology, particularly in human population biology.

Notes: Abstract The 1990 Native American Graves Protection and Repatriation Act requires universities, museums, and federal agencies to inventory their archeological collections to prepare for the repatriation of skeletons to their Native American descendants. The loss of these collections will be a detriment to the study of North American osteology, but the inventory and repatriation process has increased the number of skeletons studied from about 30% to nearly 100%. The availability of funds stimulated by this law produced osteological data collection and systematization unprecedented in the history of osteology. The possibility of forming partnerships between Native Americans and osteologists has the potential of producing a vibrant future for North American osteology and the new bioarcheology.

Notes: Abstract This review discusses changes in Amazonian indigenous anthropology since the synthesis presented in the Handbook of South American Indians. The past few years have seen the emergence of an image of Amazonia characterized by a growing emphasis on the complexity of indigenous social formations and the ecological diversity of the region. This new image of society and nature is taking shape in a theoretical context characterized by the synergistic interaction between structural and historical approaches, by an attempt to go beyond monocausal explanatory models (whether naturalistic or culturalistic) in favor of a dialectical view of the relations between society and nature, and by hopes of a "new synthesis" that could integrate the knowledge accumulated in the fields of human ecology, social anthropology, archeology, and history.

Notes: Abstract Over the past decade anthropologists and epidemiologists have begun to move beyond the "benign neglect" that characterized their prior relationship. Some of the most important collaborations between these disciplines concern themes of culture change and stress, social stratification, and the unpacking of other social and cultural variables. Anthropologists have criticized and expanded epidemiological notions of risk and vulnerability. Multidisciplinary teams of anthropologists and epidemiologists have constructed new measures and used multiple methods to increase the validity of their results. Disputes about classification have also linked the two disciplines. Collaborative projects between anthropologists and epidemiologists are leading to more nuanced and accurate descriptions of human behavior and more appropriate and effective interventions. Epidemiological techniques and ideas are also being used for anthropological ends, because disease often spreads along the framework of social structure. These many forms of collaboration create the foundations of a cultural epidemiology.

Notes: Abstract This review describes some recent, unexpected findings concerning variation in spatial language across cultures, and places them in the context of the general anthropology of space on the one hand, and theories of spatial cognition in the cognitive sciences on the other. There has been much concern with the symbolism of space in anthropological writings, but little on concepts of space in practical activities. This neglect of everyday spatial notions may be due to unwitting ethnocentrism, the assumption in Western thinking generally that notions of space are universally of a single kind. Recent work shows that systems of spatial reckoning and description can in fact be quite divergent across cultures, linguistic differences correlating with distinct cognitive tendencies. This unexpected cultural variation raises interesting questions concerning the relation between cultural and linguistic concepts and the biological foundations of cognition. It argues for more sophisticated models relating culture and cognition than we currently have available.

Notes: Abstract Paleontologists have always been concerned about the documentary quality of the fossil record, and this has also become an important issue for biologists, who increasingly look to accumulations of bones, shells, and plant material as possible ways to extend the time-frame of observation on species and community behaviors. Quantitative data on the postmortem behavior of organic remains in modern environments are providing new insights into death and fossil assemblages as sources of biological information. Important findings include: 1. With the exception of a few circumstances, usually recognizable by independent criteria, transport out of the original life habitat affects few individuals. 2. Most species with preservable hardparts are in fact represented in the local death assemblage, commonly in correct rank importance. Molluscs are the most durable of modern aquatic groups studied so far, and they show highest fidelity to the original community. 3. Time-averaging of remains from successive generations and communities often prevents the detection of short-term (seasons, years) variability but provides an excellent record of the natural range of community composition and structure over longer periods. Thus, although a complex array of processes and circumstances influences preservation, death assemblages of resistant skeletal elements are for many major groups good to excellent records of community composition, morphological variation, and environmental and geographic distribution of species, and such assemblages can record temporal dynamics at ecologically and evolutionarily meaningful scales.

Notes: Abstract Perhaps in keeping with their enigmatic name, 14-3-3 proteins offer a seemingly bewildering array of opportunities for interaction with signal transduction pathways. In each organism there are many isoforms that can form both homo- and heterodimers, and many biochemical activities have been attributed to the 14-3-3 group. The potential for diversity-and also confusion-is high. The mammalian literature on 14-3-3 proteins provides an appropriate context to appreciate the potential roles of 14-3-3s in plant signal transduction pathways. In addition, functional and structural themes emerge when 14-3-3s are examined and compiled in ways that draw attention to their participation in protein phosphorylation and protein-protein interactions. These themes allow examination of plant 14-3-3s from two perspectives: the ways in which plant 14-3- 3s contribute to and extend ideas already described in animals, and the ways that plant 14-3-3s present unique contributions to the field. The crystal structure of an animal 14-3- 3 has been solved. When considered with the evolutionary stability of large segments of the 14-3-3 protein, the structure illuminates several aspects of 14-3-3 function. However, diversity in other regions of the 14-3-3s and their presence as multigene families offer many opportunities for cell-specific specialization of individual functions.

Notes: Abstract Since plant phosphoenolpyruvate carboxylase (PEPC) was last reviewed in the Annual Review of Plant Physiology over a decade ago (O'Leary 1982), significant advances have been made in our knowledge of this oligomeric, cytosolic enzyme. This review highlights this exciting progress in plant PEPC research by focusing on the three major areas of recent investigation: the enzymology of the protein; its posttranslational regulation by reversible protein phosphorylation and opposing metabolite effectors; and the structure, expression, and molecular evolution of the nuclear PEPC genes. It is hoped that the next ten years will be equally enlightening, especially with respect to the three-dimensional structure of the plant enzyme, the molecular analysis of its highly regulated protein-Ser/Thr kinase, and the elucidation of its associated signal-transduction pathways in various plant cell types.

Notes: Abstract Nitrogen assimilation is a vital process controlling plant growth and development. Inorganic nitrogen is assimilated into the amino acids glutamine, glutamate, asparagine, and aspartate, which serve as important nitrogen carriers in plants. The enzymes glutamine synthetase (GS), glutamate synthase (GOGAT), glutamate dehydrogenase (GDH), aspartate aminotransferase (AspAT), and asparagine synthetase (AS) are responsible for the biosynthesis of these nitrogen-carrying amino acids. Biochemical studies have revealed the existence of multiple isoenzymes for each of these enzymes. Recent molecular analyses demonstrate that each enzyme is encoded by a gene family wherein individual members encode distinct isoenzymes that are differentially regulated by environmental stimuli, metabolic control, developmental control, and tissue/cell-type specificity. We review the recent progress in using molecular-genetic approaches to delineate the regulatory mechanisms controlling nitrogen assimilation into amino acids and to define the physiological role of each isoenzyme involved in this metabolic pathway.

Notes: Abstract The contribution of membrane lipids, particularly the level of unsaturation of fatty acids, to chilling sensitivity of plants has been intensively discussed for many years. We have demonstrated that the chilling sensitivity can be manipulated by modulating levels of unsaturation of fatty acids of membrane lipids by the action of acyl-lipid desaturases and glycerol-3-phosphate acyltransferase. This review covers recent studies on genetic manipulation of these enzymes in transgenic tobacco and cyanobacteria with special emphasis on the crucial importance of the unsaturation of membrane lipids in protecting the photosynthetic machinery from photoinhibition under cold conditions. Furthermore, we review the molecular mechanism of temperature-induced desaturation of fatty acids and introduce our hypothesis that changes in the membrane fluidity is the initial event of the expression of desaturase genes.

Notes: Abstract This article discusses briefly the status of energy storage technologies and explores opportunities for their application in the rapidly changing US energy marketplace. Traditionally, electric utility energy storage has been used to store low-priced purchased or generated electric energy for later sale or use when energy cost would otherwise be much higher. But deregulation and restructuring in the electric industry, coupled with an expanding portfolio of storage alternatives, may lead to many new opportunities for energy storage, especially within the energy distribution infrastructure, and for maintaining or providing power quality at large customer sites. Small, modular, robust energy storage technologies could be used to solve a range of energy supply and infrastructure-related needs. This article provides quantitative evidence of utility-related energy storage status, benefits, and opportunities.

Notes: Abstract Attaining the ambient standard for tropospheric ozone has been difficult in many metropolitan areas, despite efforts to reduce anthropogenic sources of the ozone precursors, including the nitrogen oxides (NOx). Until recently, NOx emissions from biogenic sources in soils were not considered in simulations of air quality and emissions reductions scenarios, yet they may be significant, especially in agricultural regions where nitrogen fertilizers are applied. Soil NOx is produced primarily by microbial processes; production and emissions from soils are controlled by a suite of environmental variables, including inorganic nitrogen availability, water-filled pore space, and soil temperature. Agricultural management practices such as fertilization and irrigation affect these environmental variables and thus have the potential to dramatically alter soil NOx emissions. Although current models incorporate some of these variables, accurate regional estimation of soil NOx emissions requires modeling approaches that explicitly incorporate the spatial and temporal patterns of management practices, especially fertilization, as well as other environmental controlling variables such as water-filled pore space and soil temperature.

Notes: Abstract The commercial status of the principal solar electric technologies-photovoltaic and solar thermal-is reviewed. Current and near-term market niches are identified, and projected longer-term markets are explored along with the key strategies for achieving them, including technological breakthroughs, manufacturing developments, economies of scale and mass production, and market creation. Market barriers and public policy impacts on commercialization are discussed.

Notes: Abstract The problem of security of huge stocks of weapons-usable highly enriched uranium and plutonium in Russia against theft or diversion remains a serious nonproliferation concern. During the Cold War, the security of Soviet nuclear materials was based on centralization and discipline, protection by the military, and intrusive political oversight of the people. The recent fundamental societal changes have rendered these arrangements inadequate, and the security of nuclear materials has decreased. Safeguarding nuclear materials in Russia is particularly difficult because of their very large inventories and the size and complexity of the nation's nuclear infrastructure. Russia needs a reliable and more objective technology-based system of nuclear safeguards designed to control nuclear materials. The Russian government and the international community are working towards this goal.

Notes: Abstract The energy problems of the developing world are both serious and widespread. Lack of access to sufficient and sustainable supplies of energy affects as much as 90% of the population of many developing countries. Some 2 billion people are without electricity; a similar number remain dependent on fuels such as animal dung, crop residues, wood, and charcoal to cook their daily meals. Without efficient, clean energy, people are undermined in their efforts to engage effectively in productive activities or to improve their quality of life. Developing countries are facing two crucial-and related-problems in the energy sector. The first is the widespread inefficient production and use of traditional energy sources, such as fuelwood and agricultural residues, which pose economic, environmental, and health threats. The second is the highly uneven distribution and use of modern energy sources, such as electricity, petroleum products, and liquefied or compressed natural gas, which pose important issues of economics, equity, and quality of life. To address these problems, this paper evaluates some successful programs and recommends that governments support market-oriented approaches that make the energy market equally accessible and attractive to local investors, communities, and consumers. Such approaches ideally improve access to energy for rural and poor people by revising energy pricing and by making the first costs of the transition to modern and more sustainable uses of energy more affordable.

Notes: Abstract Ethanol is a high performance fuel in internal combustion engines. It is a liquid, which is advantageous in terms of storage, delivery, and infrastructural compatability. Ethanol burns relatively cleanly, especially as the amount of gasoline with which it is blended decreases. Evaporative and toxicity-weighted air toxics emissions are consistently lower for ethanol than for gasoline. It is likely that vehicles can be configured so that exhaust emissions of priority pollutants are very low for ethanol-burning engines, although the same can probably be said for most other fuels under consideration. Recent work suggests that ethanol may be more compatible with fuel cell-powered vehicles than has generally been assumed. Research and development-driven advances have clear potential to lower the price of cellulosic ethanol to a level competitive with bulk fuels. Process areas with particular potential for large cost reductions include biological processing (with consolidated bioprocessing particularly notable in this context), pretreatment, and incorporation of an advanced power cycle for cogeneration of electricity from process residues. The cellulosic ethanol fuel cycle has a high thermodynamic efficiency (useful energy/high heating value = from 50% to over 65% on a first law basis, depending on the configuration), and a decidedly positive net energy balance (ratio of useful energy output to energy input). Cellulosic ethanol is one of the most promising technogical options available to reduce transportation sector greenhouse gas emissions. It may well be possible to develop biomass-based energy on a very large scale in the United States with acceptable and in some cases positive environmental impacts. To do so will however require responsible management and increased understanding of relevant technological and natural systems. The potential biomass resource is large, but so is demand for transportation fuels as well as other uses. The following hypotheses are offered as tentative hypotheses pertaining to biomass supply and demand in the United States: There will probably not be enough suitable land available to meet transportation demand if total vehicle miles traveled increase relative to current levels, and vehicle efficiency and animal protein utilization are unchanged. There probably is enough suitable land to meet transportation demand, even given some increase in vehicle miles traveled, given large but probably possible increases in vehicle efficiency, or large but probably possible decreases in reliance on animal protein, or a combination of less aggressive changes in both of these factors. The policy debate concerning fuel ethanol has tended to ignore cellulosic ethanol. It is suggested that an appropriate policy objective is to foster a transition to cellulosic feedstocks at a pace such that opportunities for ethanol producers and the farmers that supply them are expanded rather than contracted.