ALBERT

Notes: Abstract This review discusses pharmaceuticals as social and cultural phenomena by following their "life cycle" from production, marketing, and prescription to distribution, purchasing, consumption, and finally their efficacy. Each phase has its own particular context, actors, and transactions and is characterized by different sets of values and ideas. The anthropology of pharmaceuticals is relevant to medical anthropology and health policy. It also touches the heart of general anthropology with its long-time interest in the concepts of culture vs nature, symbolization and social transformation, and its more recent concerns with the cultural construction of the body and processes of globalization and localization. The study of transactions and meanings of pharmaceuticals in diverse social settings provides a particularly appropriate empirical base for addressing these new theoretical issues.

Notes: Abstract Grammaticalization-the transformation of lexical items and phrases into grammatical forms-has been the focus of considerable study. Two chief directions can be identified. The first involves etymology and the taxonomy of possible changes in language, in which semantic and cognitive accounts of words and categories of words are considered to explain the changes. The second involves the discourse contexts within which grammaticalization occurs. Some researchers have questioned the standard idea of a stable synchronic a priori grammar in which linguistic structure is distinct from discourse, and have sought to replace this with the idea of "emergent grammar" in which repetitions of various kinds in discourse lead to perpetual structuration.

Notes: Abstract The past decade has seen a dramatic increase in the number of fossil human specimens discovered in China. A better understanding of the tempo and mode of human evolution in Asia during the Pleistocene can be gained as a result. This new evidence has important implications for understanding the course of human evolution not only in Asia but throughout the world. Major issues in human evolutionary studies such as the timing of the initial hominid dispersal event and the factors behind major transitions in the fossil record are addressed in light of these recent finds.

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 The review focuses on analyses of the creation of culture among poor populations in the United States whose lives have been structured by residing at the center of the global economy. Literature is examined concerning the changing construction of labor, space, time, and identity in the new poverty. Throughout, the review examines the generation of poverty and questions of gender, race, political mobilization, and resistance. This outline of current research provides a framework for an analysis of the violence and conflict generated by the lowering of wages and the reduction of leisure time.

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 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 For decades cell biologists have relied on viruses to facilitate the study of complex cellular function. More recently, the tragedy of the AIDS epidemic has focused considerable human and financial resources on both virology and immunology, resulting in the generation of new information relating these disciplines. As the miracle of the mammalian immune system unfolds in the laboratory, the elegance of the mechanisms used by co-evolving viruses to circumvent detection and destruction by the host becomes inescapably obvious. Although many observations of virus-induced phenomena that likely contribute to the virus's escape of immune surveillance are still empirical, many other such phenomena have now been defined at the molecular level and confirmed in in vivo models. Immune modulators encoded within viral genomes include proteins that regulate antigen presentation, function as cytokines or cytokine antagonists, inhibit apoptosis, and interrupt the complement cascade. The identification of such gene products and the elucidation of their function have substantially strengthened our understanding of specific virus-host interactions and, unexpectedly, have contributed to the recognition of potent synergy between viruses, which can result in an unpredictable exacerbation of disease in co-infected individuals. Because many viral immune modulators clearly have host counterparts, viruses provide a valuable method for studying normal immune mechanisms. It is conceivable that an improved understanding of virus-encoded immunomodulators will enhance our ability to design reagents for use in therapeutic intervention in disease and in vaccine development.

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 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 Major histocompatibility complex (MHC) class I molecules bind peptides derived from cellular proteins and display them for surveillance by the immune system. These peptide-binding molecules are composed of a heavy chain, containing an antigen-binding groove, which is tightly associated with a light chain (beta2-microglobulin). The majority of presented peptides are generated by degradation of proteins in the cytoplasm, in many cases by a large multicatalytic proteolytic particle, the proteasome. Two beta-subunits of the proteasome, LMP2 and LMP7, are inducible by interferon-gamma and alter the catalytic activities of this particle, enhancing the presentation of at least some antigens. After production of the peptide in the cytosol, it is transported across the endoplasmic reticulum (ER) membrane in an ATP-dependent manner by TAP (transporter associated with antigen presentation), a member of the ATP-binding cassette family of transport proteins. There are minor pathways for generating presented peptides directly in the ER, and some evidence suggests that peptides may be further trimmed in this location. The class I heavy chain and beta2-microglobulin are cotranslationally translocated into the endoplasmic reticulum where their assembly may be facilitated by the sequential association of the heavy chain with chaperone proteins BiP and calnexin. The class I molecule then associates with the lumenal face of TAP where it is retained, presumably awaiting a peptide. After the class I molecule binds a peptide, it is released for exocytosis to the cell surface where cytotoxic T lymphocytes examine it for peptides derived from foreign proteins.

Notes: Abstract The chlorophyll-carotenoid binding proteins responsible for absorption and conversion of light energy in oxygen-evolving photosynthetic organisms belong to two extended families: the Chl a binding core complexes common to cyanobacteria and all chloroplasts, and the nuclear-encoded light-harvesting antenna complexes of eukaryotic photosynthesizers (Chl a/b, Chl a/c, and Chl a proteins). There is a general consensus on polypeptide and pigment composition for higher plant pigment proteins. These are reviewed and compared with pigment proteins of chlorophyte, rhodophyte, and chromophyte algae. Major advances have been the determination of the structures of LHCII (major Chl a/b complex of higher plants), cyanobacterial Photosystem I, and the peridinen-Chl a protein of dinoflagellates to atomic resolution. Better isolation methods, improved transformation procedures, and the availability of molecular structure models are starting to provide insights into the pathways of energy transfer and the macromolecular organization of thylakoid membranes.

Notes: Abstract Molecular studies of drought stress in plants use a variety of strategies and include different species subjected to a wide range of water deficits. Initial research has by necessity been largely descriptive, and relevant genes have been identified either by reference to physiological evidence or by differential screening. A large number of genes with a potential role in drought tolerance have been described, and major themes in the molecular response have been established. Particular areas of importance are sugar metabolism and late-embryogenesis-abundant (LEA) proteins. Studies have begun to examine mechanisms that control the gene expression, and putative regulatory pathways have been established. Recent attempts to understand gene function have utilized transgenic plants. These efforts are of clear agronomic importance.

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 Across cultures, narrative emerges early in communicative development and is a fundamental means of making sense of experience. Narrative and self are inseparable in that narrative is simultaneously born out of experience and gives shape to experience. Narrative activity provides tellers with an opportunity to impose order on otherwise disconnected events, and to create continuity between past, present, and imagined worlds. Narrative also interfaces self and society, constituting a crucial resource for socializing emotions, attitudes, and identities, developing interpersonal relationships, and constituting membership in a community. Through various genres and modes; through discourse, grammar, lexicon, and prosody; and through the dynamics of collaborative authorship, narratives bring multiple, partial selves to life.

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 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 This chapter reviews what is presently known about the sudden infant death syndrome (SIDS) and examines the role that infant sleeping arrangements may play in reducing SIDS risks. Alongside sleep laboratory-based experimental evidence comparing bedsharing and solitary sleeping mother-infant pairs, an evolutionary and cross-cultural framework is used to argue that infant-parent cosleeping is biologically, psychologically, and socially the most appropriate context for the development of healthy infant sleep physiology. It is also the context within which potentially more optimal breastfeeding activities for both the mother and infant are most likely to emerge. A survey of cross-cultural data and laboratory findings suggest that where infant-parent cosleeping and breastfeeding are practiced in tandem in nonsmoking households, and are practiced by parents specifically to promote infant health, the chances of an infant dying from SIDS should be reduced.

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 Conservation programs for protected areas and plant genetic resources have evolved in similar ways, beginning with a focus on single species and expanding to ecosystem strategies that involve the participation of local people. Anthropologists have described the increasing importance of the participation of local people in conservation programs, both of local populations in protected area management and of farmers in plant genetic resources. Both protected areas and plant genetic resources link local populations, national agencies, and international organizations. Anthropological research (a) documents local knowledge and practices that influence the selection and maintenance of crop varieties and the conservation of rare and endangered species in protected areas, and (b) clarifies the different concerns and definitions of biodiversity held by local populations and international conservationists. In addition, anthropologists operate in nongovernmental organizations (NGOs) and international agencies, participating in policy debates and acting as advocates and allies of local populations of farmers and indigenous peoples.

Notes: Abstract Although the temperature at the top of the lower mantle is well constrained by phase equilibrium data for the transformation of transition zone minerals to the denser perovskite polymorphs, the temperature distribution in the lower mantle is poorly known. Models depend strongly on the assumptions of the amount of internal heating and the viscosity profile. New melting data on iron to pressures of the outer core (2 Mbar) and the observed strong decrease of eutectic melting depression in the Fe-FeO-FeS system with increasing pressure, however, tightly constrain the temperature at the inner-core boundary to slightly less than 5000 K. This estimate can be reconciled with all recent static melting measurements on iron and lays within the uncertainty of shock temperature measurements. The resulting temperature at the core-mantle boundary of about 4000 K then requires a large temperature gradient at the bottom of the lower mantle of about 1500 K. Recent findings of the very high melting temperatures of the major lower-mantle materials Mg-Si-perovskite and magnesiowustite indicate that this increase in temperature does not cause melting in the lower mantle.

Notes: Abstract Io, innermost of Jupiter's large moons, is one of the most unusual objects in the Solar System. Tidal heating of the interior produces a global heat flux 40 times the terrestrial value, producing intense volcanic activity and a global resurfacing rate averaging perhaps 1 cm yr-1. The volcanoes may erupt mostly silicate lavas, but the uppermost surface is dominated by sulfur compounds including SO2 frost. The volcanoes and frost support a thin, patchy SO2 atmosphere with peak pressure near 10-8 bars. Self-sustaining bombardment of the surface and atmosphere by Io-derived plasma trapped in Jupiter's magnetosphere causes escape of material from Io (predominantly sulfur, oxygen, and sodium atoms, ions, and molecules) at a rate of about 103 kg s-1. The resulting Jupiter-encircling torus of ionized sulfur and oxygen dominates the Jovian magnetosphere and, together with an extended cloud of neutral sodium, is readily observable from Earth.

Notes: Abstract Seismic anisotropy beneath continents is analyzed from shear-wave splitting recorded at more than 300 continental seismic stations. Anisotropy is found to be a ubiquitous property that is due to mantle deformation from past and present orogenic activity. The observed coherence with crustal deformation implies that the mantle plays a major, if not dominant, role in orogenies. No evidence is found for a continental asthenospheric decoupling zone, suggesting that continents are coupled to general mantle circulation.

Notes: Abstract Recent advances in computational physics allow numerical simulation of three-dimensional complex flows through arbitrarily complex geometries. Moreover, new technology for noninvasive imaging provides detailed three-dimensional tomographic reconstructions of porous rocks with a resolution approaching one micron. These two innovations are leading to new understanding of how the microscopic complexity of natural porous media influences fluid transport at a larger, macroscopic scale. This review describes new insights concerning single-phase and multiphase porous flow derived from numerical simulation. In particular, results concerning scaling relations between macroscopic parameters, the scale dependence of transport properties, and viscous coupling in multicomponent flow are emphasized.

Notes: Abstract Geophysical estimates of mid-ocean ridge axial heat fluxes (2-4 x 1012 W) and of the total hydrothermal flux (9 +- 2 x 1012 W) are well established. Problems arise in calculation of water fluxes because of uncertainties in (a) values of off-axis fluxes and (b) the partition of axial heat flow between high-temperature black smoker and lower-temperature diffuse flow. Of the various geochemical methods of estimating fluxes, 3 He/heat data are extremely variable, the Mg method is sensitive to flank fluxes, Sr isotopes agree with geophysical estimates only if flank fluxes are important, Li isotopes data are consistent with geophysical values, and Ge/Si ratios give low fluxes, which may reflect low-temperature processes not yet fully quantified. Estimates of hydrothermal heat and water fluxes derived from these approaches are presented as are hydrothermal chemical fluxes at the ridge axis, off axis, and as affected by hydrothermal plumes.

Notes: Abstract Continental North America's greatest earthquake sequence struck on the western frontier of the United States. The frontier was not then California but the valley of the continent's greatest river, the Mississippi, and the sequence was the New Madrid earthquakes of the winter of 1811-1812. Their described impacts on the land and the river were so dramatic as to produce widespread modern disbelief. However, geological, geophysical, and historical research, carried out mostly in the past two decades, has verified much in the historical accounts. The sequence included at least six (possibly nine) events of estimated moment magnitude M〉= 7 and two of M= 8. The faulting was in the intruded crust of a failed intracontinental rift, beneath the saturated alluvium of the river valley, and its violent shaking resulted in massive and extensive liquefaction. The largest earthquakes ruptured at least six (and possibly more than seven) intersecting fault segments, one of which broke the surface as a thrust fault that disrupted the bed of the Mississippi River in at least 2 (and possibly four) places. ...it is a riddle wrpped in a mystery inside an enigma. Winston Churchill

Notes: Abstract Interactions between stromal cells and thymocytes play a crucial role in T cell development. The thymic stroma is complex and consists of epithelial cells derived from the pharyngeal region during development, together with macrophages and dendritic cells of bone marrow origin. In addition, fibroblasts and matrix molecules permeate the whole framework. It is now apparent that these individual stromal components play specialized roles at different stages of T cell differentiation. Thus, at the early CD4-8- stage of development, T cell precursors require fibroblast as well as epithelial cell interactions. Later, at the CD4+8+ stage, as well as providing low avidity TCR/MHC-peptide interactions, thymic epithelial cells have been shown to possess unique properties essential for positive selection. Dendritic cells, on the other hand, are probably efficient mediators of negative selection, but they may not be solely responsible for this activity. Alongside the functional roles of stromal cells, considerable progress is being made in unraveling the nature of the signaling pathways involved in T cell development. Identification of the pre-T cell receptor (pre-TCR) and associated signaling molecules marks an important advance in understanding the mechanisms that control gene rearrangement and allelic exclusion. In addition, a better understanding of the signaling pathways that lead to positive selection on the one hand and negative selection on the other is beginning to emerge. Many issues remain unresolved, and some are discussed in this review. What, for example, is the nature of the chemotactic factor(s) that attract stem cells to the thymus? What is the molecular basis of the essential interactions between early thymocytes and fibroblasts, and early thymocytes and epithelial cells? What is special about cortical epithelial cells in supporting positive selection? These and other issues are ripe for analysis and can now be approached using a combination of modern molecular and cellular techniques.

Notes: Abstract The earliest steps along the pathway leading to T cells in mice and humans are reviewed. These are the steps between the multipotent hemopoietic stem cell (HSC) and the fully committed precursors undergoing T cell receptor (TCR) gene rearrangement. At this level significant differences between adult and fetal lymphopoiesis have been demonstrated. The extent of lymphoid commitment of precursors within bone marrow is still unresolved, although HSCs clearly undergo developmental changes before migration to the thymus. Both multipotent and T-restricted precursors have now been isolated from fetal blood, suggesting both may seed the thymus. Within the thymus, several minute but discrete populations of T precursors precede the stage of TCR gene rearrangement. They include precursors that are not exclusively T-lineage committed, although they are distinct from HSCs. These precursors have a potential to form NK cells, B cells, dendritic cells, and sometimes other myeloid cells. Some factors that control early lymphoid development are discussed, including IL-7 and the Ikaros transcription factors. These will eventually help to clarify the process of T-lineage commitment.

Notes: Abstract The elucidation of the phenomena of T cell antagonism and partial activation by altered peptide ligands has necessitated a revision in the traditional concepts of TCR recognition of antigen and subsequent signal transduction. Whereas previous models supported a single ligand specificity for any particular T cell, many studies using analogs of immunogenic peptides have now demonstrated a flexibility in this recognition. Moreover, interaction with such altered peptide ligands can result in dramatically different phenotypes of the T cells, ranging from inducing selective stimulatory functions to completely turning off their functional capacity. Investigations of the biochemical basis leading to these phenotypes have shown that altered peptide ligands can induce a qualitatively different pattern of signal transduction events than does any concentration of the native ligand. Such observations imply that several signaling modules are directly linked to the TCR/CD3 complex and that they can be dissociated from each other as a direct result of the nature of the ligand bound. Interestingly, many in vivo models of T cell activation are compatible with a selective signaling model, and several studies have shown that peptide analogs can play a role in various T cell biologic phenomena. These data strongly suggest that naturally occurring altered peptide ligands for any TCR exist in the repertoire of self-peptides or, in nature, derived from pathogens, and recent reports provide compelling evidence that this is indeed the case. The concept of altered peptide ligands, their effects on T cell signaling, the hypothesized mechanisms by which they exert their effects, and their possible roles in shaping the T cell immune response are the scope of this review.

Notes: Abstract The specificity and efficiency of leukocyte binding to endothelial cells (ECs) depends on coordinated information transfer from the underlying tissue to endothelium and from there to the leukocyte. We address three distinct information-transfer points in this system: 1. How does the leukocyte read information from the EC? This process is best accounted for by the paradigm of a multi-step adhesion cascade optimized for rapid information readout; it consists of primary adhesion (rolling/tethering), triggering, and strong adhesion. Recent studies with T cells, monocytes, and eosinophils confirm the generality of the paradigm. The concept of primary adhesion has been expanded to involve not only the selectins, but also certain integrins; furthermore, it depends on receptor concentration on leukocyte microvilli. 2. What information from the underlying tissue does the EC transform into signals for the leukocytes? And what rules govern that process? We illustrate the principles with chemokines, believed to participate in the triggering step. The endothelium displays chemokines either (a) directly by "posting" them from other cells or (b) by integrating a variety of tissue and environmental signals and "relaying" that information by producing its own chemokines and surface adhesion molecules. The rules for this endothelial transduction include specificity coupled with redundancy, amplification, synergy, and coordinated induction of ensembles of molecules. Finally, 3. How does the relevant information reach the endothelium? Simple diffusion is sufficient to deliver signals from cells close to the vessel. However, longer range soluble mediator transport appears to be facilitated by fiber bundles, particularly those ensheathed by fibroblastic reticular cells in the lymph node.

Notes: Abstract The relationship between somatic hypermutation and affinity maturation in the mouse is delineated. Recent work on the anatomical and cellular site of this process is surveyed. The molecular characteristics of somatic hypermutation are described in terms of the region mutated and the distinctive patterns of nucleotide changes that are observed. The results of experiments utilizing transgenic mice to find out the minimum cis-acting sequences required to recruit hypermutation are summarized. The hypothesis that V gene sequences have evolved in order to target mutation to certain sites but not others is discussed. The use that different species make of somatic hypermutation to generate either the primary or secondary B cell repertoire is considered. Possible molecular mechanisms for the hypermutation process and future goals of research are outlined.

Notes: Abstract Over the past three years, CD40 and its ligand (gp39, CD40L, TBAM) have been shown to be essential for humoral immune responses to thymus-dependent antigens. However, as the tissue distribution widens for those cells that express CD40 and gp39, we can now show that this ligand-receptor pair also plays an important role in the selection of self-reactive T cells in the thymus (central tolerance) and the regulation of tolerance in mature T cells (peripheral tolerance). Advances in our understanding of the molecular basis for CD40 biology is based in two areas of research. First, a major breakthrough in our understanding of how CD40 transduces biological events centers on the identification of a novel protein that binds to the cytoplasmic tail of CD40 and may act as a signal transducing molecule. Secondly, advances in molecular modeling and mutagenesis of this ligand-receptor pair have helped to identify the critical receptor/ligand contacts in the gp39/CD40 complex. Advances in each of these areas are discussed.

Notes: Abstract Natural killer cells are likely to play an important role in the host defenses because they kill virally infected or tumor cells but spare normal self-cells. The molecular mechanism that explains why NK cells do not kill indiscriminately has recently been elucidated. It is due to several specialized receptors that recognize major histocompatibility complex (MHC) class I molecules expressed on normal cells. The lack of expression of one or more class I alleles leads to NK-mediated target cell lysis. During NK cell development, the class I-specific receptors have adapted to self-class I molecules on which they recognize epitopes shared by groups of class I alleles. As such, they may fail to recognize either self-molecules that bound unusual peptides or allogeneic class I molecules unrelated to self-alleles. Different types of receptors specific for groups of HLA-C or HLA-B alleles have been identified. While in most instances, they function as inhibiting receptors, an activating form of the HLA-C-specific receptors has been identified in some donors. Molecular cloning of HLA-C- and HLA-B-specific receptors has revealed new members of the immunoglobulin superfamily with two or three Ig-like domains, respectively, in their extracellular portion. While the inhibiting form is characterized by a long cytoplasmic tail associated with a nonpolar transmembrane portion, the activating one has a short tail associated with a Lys-containing transmembrane portion. Thus, these human NK receptors are different from the murine Ly49 that is a type II transmembrane protein characterized by a C type lectin domain. A subset of cytolytic T lymphocytes expresses NK-type class I-specific receptors. These receptors exert an inhibiting activity on T cell receptor-mediated functions and offer a valuable model to analyze the regulatory mechanisms involved in receptor-mediated cell activation and inactivation.

Notes: The chapter provides a personal and anecdotal account of the author's attempts to keep the horizons of advancing science in sight. It sketches his background to entering science and chronicles various episodes across fifty years in research. Milestones are noted on the author's journey from his structural studies on colchicine, griseofulvin, and gibberellic acid to the isolation, analysis, biosynthesis, and molecular biology of plant gibberellins. The author discusses his personal and professional interactions with plant physiologists and plant biochemists over the years. Philosophical observations are offered on some of the attributes important to conducting research and on changing attitudes toward research.

Notes: Abstract Homology-dependent gene silencing phenomena in plants have received considerable attention, especially when it was discovered that the presence of homologous sequences not only affected the stability of transgene expression, but that the activity of endogenous genes could be altered after insertion of homologous transgenes into the genome. Homology-mediated inactivation most likely comprises at least two different molecular mechanisms that induce gene silencing at the transcriptional or posttranscriptional level, respectively. In this review we discuss different mechanistic models for plant-specific inactivation mechanisms and their relationship with repeat-specific silencing phenomena in other species.

Notes: Abstract The biological impact of any DNA damaging agent is a combined function of the chemical nature of the induced lesions and the efficiency and accuracy of their repair. Although much has been learned from microbes and mammals about both the repair of DNA damage and the biological effects of the persistence of these lesions, much remains to be learned about the mechanism and tissue-specificity of repair in plants. This review focuses on recent work on the induction and repair of DNA damage in higher plants, with special emphasis on UV-induced DNA damage products.

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 Lipid-transfer proteins (LTP) are basic, 9-kDa proteins present in high amounts (as much as 4% of the total soluble proteinss) in higher plants. LTPs can enhance the in vitro transfer of phospholipids between membranes and can bind acyl chains. On the basis of these properties, LTPs were thought to participate in membrane biogenesis and regulation of the intracellular fatty acid pools. However, the isolation of several cDNAs and genes revealed the presence of a signal peptide indicating that LTPs could enter the secretory pathway. They were found to be secreted and located in the cell wall. Thus, novel roles were suggested for plant LTPs: participation in cutin formation, embryogenesis, defense reactions against phytopathogens, symbiosis, and the adaptation of plants to various environmental conditions. The validity of these suggestions needs to be determined, in the hope that they will elucidate the role of this puzzling family of plant proteins.

Notes: Abstract When plants are exposed to light intensities in excess of those that can be utilized in photosynthetic electron transport, nonphotochemical dissipation of excitation energy is induced as a mechanism for photoprotection of photosystem II. The features of this process are reviewed, particularly with respect to the molecular mechanisms involved. It is shown how the dynamic properties of the proteins and pigments of the chlorophyll a/b light-harvesting complexes of photosystem II first enable the level of excitation energy to be sensed via the thylakoid proton gradient and subsequently allow excess energy to be dissipated as heat by formation of a nonphotochemical quencher. The nature of this quencher is discussed, together with a consideration of how the variation in capacity for energy dissipation depends on specific features of the composition of the light-harvesting system. Finally, the prospects for future progress in understanding the regulation of light harvesting are assessed.

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 Numerous bacteria have been isolated from within plants, and many reported from xylem, but only three species of xylem-limited bacteria (XLB) that are fastidious in cultural requirements, are plant pathogens, and exclusively occupy xylem, have been well characterized. Two XLB, Xylella fastidiosa and Pseudomonas syzygii, are transmitted by sucking insects that feed on xylem sap but are not transmitted mechanically from plant to plant. In contrast, Clavibacter xyli is mechanically transmitted to plants by cutting tools. All of these XLB occupy a highly specialized yet diverse ecological niche: the water-conducting systems of an extremely wide range of plant hosts. A variety of detection methods are available as diagnostic aids; each method has advantages and disadvantages; no single method is best for all uses. Molecular and genetic comparisons of strains of XLB lag behind progress being made for many other plant-pathogenic bacteria, but such studies are needed to answer important questions: (a) How do XLB move from cell to cell within plants? (b) What are the physiological and genetic bases of plant host specificity for XLB? (c) Why are only xylem-feeding specialists vectors of X. fastidiosa (and probably P. syzygii), when many leafhoppers feed regularly (but not continuously) on xylem?

Notes: The Department of Plant Pathology at the University of California at Berkeley was destroyed as a consequence of a contentious reorganization. The circumstances that led to the reorganization provide some insight into the challenges facing the discipline of plant pathology. The underlying basis for plant pathology as a science is to address problems of plant disease. This requires a balance between disciplinary and problem-solving research and a continuum from achieving fundamental advances in knowledge to the development and implementation of problem-solving approaches. Changes in colleges and universities have placed extreme stress on this essential structure. The dilemma that must be addressed is how to reestablish the problem-solving continuum where it has been broken and strengthen it where it has been weakened. Plants are essential for life, and they will always be affected by disease. The understanding and management of these diseases is the responsibility and the challenge of plant pathology today and in the future.

Notes: Swiss-born Dr. Gotthold Steiner was a pioneer in formulating the discipline of nematology. He worked with the American nematologist NA Cobb and together they were responsible for acceptance of the concept of nematode phytoparasites. Steiner had special expertise in anatomy, morphology, phytonematology, marine nematodes, nutrition, mermithids, and selected invertebrate taxa. He authored 191 scientific papers, established the ubiquitous phytoparasitic genus Helicotylenchus, described the pinewood nematode, and did significant work with three important economic pests, Ditylenchus dipsaci, Heterodera rostochiensis, and H. schachtii. He was responsible for introducing training programs in nematology in USDA laboratories.

Notes: Abstract Although more than 30 bacterial avirulence genes have been cloned and characterized, the function of the gene products in the elictitation of resistance is unknown in all cases but one. The product of avrD from Pseudomonas syringae pv. glycinea likely functions indirectly to elicit resistance in soybean, that is, evidence suggests the gene product is an enzyme involved in elicitor production. In most if not all cases, bacterial avirulence gene function is dependent on interactions with the hypersensitive response and pathogenicity (hrp) genes. Many hrp genes are similar to genes involved in delivery of pathogenicity factors in mammalian bacterial pathogens. Thus, analogies between mammalian and plant pathogens may provide needed clues to elucidate how virulence gene products control induction of resistance.

Notes: Abstract The 15 known viruses that occur in rice are rice black-streaked dwarf, rice bunchy stunt, rice dwarf, rice gall dwarf, rice giallume, rice grassy stunt, rice hoja blanca, rice necrosis mosaic, rice ragged stunt, rice stripe necrosis, rice stripe, rice transitory yellowing, rice tungro bacilliform, rice tungro spherical, and rice yellow mottle viruses. This paper describes their geographical distribution, relation to vectors, infection cycles, field dispersal, and development, and lists recorded outbreaks of the viruses. Many rice viruses have become serious problems since rice cultivation has been intensified. Double-cropping of rice using improved, photo-insensitive cultivars of short growth duration has significantly influenced the incidence of these viruses.

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

Notes: Abstract Quantitative trait locus (QTL) mapping is a highly effective approach for studying genetically complex forms of plant disease resistance. With QTL mapping, the roles of specific resistance loci can be described, race-specificity of partial resistance genes can be assessed, and interactions between resistance genes, plant development, and the environment can be analyzed. Outstanding examples include: quantitative resistance to the rice blast fungus, late blight of potato, gray leaf spot of maize, bacterial wilt of tomato, and the soybean cyst nematode. These studies provide insights into the number of quantitative resistance loci involved in complex disease resistance, epistatic and environmental interactions, race-specificity of partial resistance loci, interactions between pathogen biology, plant development and biochemistry, and the relationship between qualitative and quantitative loci. QTL mapping also provides a framework for marker-assisted selection of complex disease resistance characters and the positional cloning of partial resistance genes.

Notes: Abstract Origins of Theobroma cacao and Crinipellis perniciosa occurred in the Amazon Basin region of South America, and their interaction, the witches' broom disease, was first described in the late 1700s. The 100 years of scientific investigations of witches' broom of cacao that began in the 1890s developed the present state of knowledge of the biology and epidemiology of witches' broom that are discussed. Recommended management to reduce the deleterious effects of witches' broom on cacao production include the use of phytosanitation (removal of diseased plant parts), applications of chemical fungicides, and the use of host resistance. At present, there is a paucity of resistant planting materials, and efforts to evaluate germplasm for resistance to witches' broom are described. Research topics to augment present knowledge about witches' broom of cacao are presented with the hope that disease management can be improved.

Notes: Abstract The role and functioning of the anterior chemosensory organs of plant parasitic nematodes is examined, with particular emphasis on the amphids. The morphology of the amphids is discussed primarily in the context of the changes in the ultrastructure associated with different life stages. The involvement of amphidial secretions in chemoreception and the behavioral and electrophysiological analyses of nematode responses to semiochemicals are discussed with special reference to research on sex pheromones. These research techniques, combined with the use of lectins and antibodies, provide information on nematode sensilla that may lead to novel control strategies for economically important plant parasitic nematodes based on perturbing nematode sensory perception to prevent host or mate location.

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

Notes: Abstract Leaf rust (caused by Puccinia recondita f. sp. tritici) is the most widespread and regularly occurring rust on wheat. Genetic resistance is the most economical method of reducing yield losses due to leaf rust. To date, 46 leaf rust resistance genes have been designated and mapped in wheat. Resistance gene expression is dependent on the genetics of host-parasite interaction, temperature conditions, plant developmental stage, and interaction between resistance genes with suppressors or other resistance genes in the wheat genomes. Genes expressed in seedling plants have not provided long-lasting effective leaf rust resistance. Adult-plant resistance genes Lr13 and Lr34 singly and together have provided the most durable resistance to leaf rust in wheat throughout the world. Continued efforts to isolate, characterize, and map leaf rust resistance genes is essential given the ability of the leaf rust fungus to overcome deployed resistance genes.

Notes: Abstract Recent data from the Tevatron collider have revealed that the production rate of prompt charmonium at large transverse momentum is orders of magnitude larger than the best theories of a few years ago had predicted. These surprising results can be understood by taking into account two recent developments that have dramatically revised the theoretical description of heavy-quarkonium production. The first is the realization that fragmentation must dominate at large transverse momentum, which implies that most charmonium in this kinematic region is produced by the hadronization of individual high-pT partons. The second is the development of a factorization formalism for quarkonium production based on nonrelativistic QCD that allows the formation of charmonium from color-octet pairs to be treated systematically. This review summarizes these theoretical developments and their implications for quarkonium production in high-energy colliders.

Notes: Abstract A mesoscopic system with strong interaction between constituents, the atomic nucleus is a good candidate for studying the manifestations of quantum chaos. Recent experimental and theoretical developments give clear evidence of the dominant role chaotic dynamics plays not only in local level statistics, but also in the damping of collective motion, isospin and parity nonconservation, thermalization, and decay into continuum. In this review, those and other phenomena are discussed from the general viewpoint of quantum chaos and complexity. The complexity of eigenstates measured by information entropy in the mean-field basis is more informative than the standard signatures of chaos in the level statistics. It evolves regularly as a function of excitation energy and provides an alternative temperature scale. This sheds new light on the problems of foundations of statistical mechanics and quantum decoherence.

Notes: Abstract This review discusses the experimental and theoretical status of various parton-model sum rules. The basis of the sum rules in perturbative quantum chromodynamics is discussed. Their use in extracting the value of the strong coupling constant is evaluated, and the failure of the naive version of some of these sum rules is assessed.