ALBERT

Notes: Abstract The vast surface of the plant axis, stretching from root tips occasionally buried deeply in anoxic sediment, to apical meristems held far aloft, provides an extraordinarily diverse habitat for microorganisms. Each zone has to a greater or lesser extent its own cohort of microorganisms, in aggregate comprising representatives from all three primary domains of life-Bacteria, Archaea, and Eucarya. While the plant sets the stage for its microbial inhabitants, they, in turn, have established varied relationships with their large partner. These associations range from relatively inconsequential (transient epiphytic saprophytes) to substantial (epiphytic commensals, mutualistic symbionts, endophytes, or pathogens). Through recent technological breakthroughs, a much better perspective is beginning to emerge on the nature of these relationships, but still relatively little is known about the role of epiphytic microbial associations in the life of the plant.

Notes: Abstract Although evidence for horizontal gene transfer (HGT) in eukaryotes remains largely anecdotal, literature on HGT in fungi suggests that it may have been more important in the evolution of fungi than in other eukaryotes. Still, HGT in fungi has not been widely accepted because the mechanisms by which it may occur are unknown, because it is usually not directly observed but rather implied as an outcome, and because there are often equally plausible alternative explanations. Despite these reservations, HGT has been justifiably invoked for a variety of sequences including plasmids, introns, transposons, genes, gene clusters, and even whole chromosomes. In some instances HGT has also been confirmed under experimental conditions. It is this ability to address the phenomenon in an experimental setting that makes fungi well suited as model systems in which to study the mechanisms and consequences of HGT in eukaryotic organisms.

Notes: Abstract The unique coenocytic anatomy of the mycelia of the filamentous fungi and the formation of anastomoses between hyphae from different mycelia enable the intracellular accumulation and infectious transmission of plasmids and mutant mitochondrial DNAs (mtDNAs) that cause senescence. For reasons that are not fully apparent, mitochondria that are rendered dysfunctional by so-called "suppressive" mtDNA mutations proliferate rapidly in growing cells and gradually displace organelles that contain wild-type mtDNA molecules and are functional. The consequence of this process is senescence and death if the suppressive mtDNA contains a lethal mutation. Suppressive mtDNA mutations and mitochondrial plasmids can elicit cytoplasmically transmissible "mitochondrial hypovirulence" syndromes in at least some of the phytopathogenic fungi. In the chestnut-blight fungus Cryphonectria parasitica, the pattern of asexual transmission of mutant mtDNAs and mitochondrial plasmids resembles the pattern of "infectious" transmission displayed by the attenuating virus that is most commonly used for the biological control of this fungus. At least some of the attenuating mitochondrial hypovirulence factors are inherited maternally in crosses, whereas the viruses are not transmitted sexually. The natural control of blight in an isolated stand of chestnut trees has resulted from the invasion of the local population of C. parasitica by a senescence-inducing mutant mtDNA. Moreover, a mitochondrial plasmid, pCRY1, attenuates at least some virulent strains of C. parasitica, suggesting that such factors could be applied to control plant diseases caused by fungi.

Notes: I first describe my introduction to plant pathology and early experiences with employment, the environment, diseases, pests, and various plant pathologists. Then I recount a decade of stimulating studies at the University of Minnesota and the route I followed to a career in international agriculture with the Rockefeller Foundation in Colombia and later at Cornell University. My appreciation for and knowledge of traditional farmers and sustainable agriculture occurred as a slow awakening. Comments are made regarding problems, principles, and satisfactions associated with the improvement of efforts to aid food production in developing countries. My curious love affair with root and tuber crops, especially cassava, is explained and readily defended. My favorite pathogens, Phytophthora infestans and Ralstonia solanacearum, among others, are considered. The pleasures and satisfactions of teaching, writing, and sabbatical leaves are related. Finally, thoughts on the balance between basic and applied research in plant pathology are offered with significant nervousness about the future of our discipline.

Notes: Abstract Nineteen single dominant genes (R genes) for resistance to viruses, nematodes, and fungi have been positioned on the molecular map of potato using DNA markers. Fourteen of those genes are located in five "hotspots" for resistance in the potato genome. Quantitative trait loci (QTL) for resistance to late blight caused by the oomycete Phytophthora infestans, to tuber rot caused by the bacterium Erwinia carotovora ssp. atroseptica, and to root cyst nematodes have been identified on all 12 potato chromosomes. Some QTL for resistance to different pathogens are linked to each other and/or to resistance hotspots. Based on the genetic clustering with R genes, we propose that some QTL for resistance have a molecular basis similar to single R genes. Mapping potato genes with sequence similarity to cloned R genes of other plants and other defense-related genes reveals linkage between candidate genes, R genes, and resistance QTL. To explain the molecular basis of polygenic resistance in potato we propose (a) genes having structural similarity with cloned R genes and (b) genes involved in the defense response. The "candidate gene approach" enables the identification of markers highly useful for marker-assisted selection in potato breeding.

Notes: Abstract The controlled environment of greenhouses, the high value of the crops, and the limited number of registered fungicides offer a unique niche for the biological control of plant diseases. During the past ten years, over 80 biocontrol products have been marketed worldwide. A large percentage of these have been developed for greenhouse crops. Products to control soilborne pathogens such as Sclerotinia, Pythium, Rhizoctonia and Fusarium include Coniothyrium minitans, species of Gliocladium, Trichoderma, Streptomyces, and Bacillus, and nonpathogenic Fusarium. Products containing Trichoderma, Ampelomyces quisqualis, Bacillus, and Ulocladium are being developed to control the primary foliar diseases, Botrytis and powdery mildew. The development of Pseudomonas for the control of Pythium diseases in hydroponics and Pseudozyma flocculosa for the control of powdery mildew by two Canadian research programs is presented. In the future, biological control of diseases in greenhouses could predominate over chemical pesticides, in the same way that biological control of greenhouse insects predominates in the United Kingdom. The limitations in formulation, registration, and commercialization are discussed, along with suggested future research priorities.

Notes: Abstract Populations of plant viruses, like all other living beings, are genetically heterogeneous, a property long recognized in plant virology. Only recently have the processes resulting in genetic variation and diversity in virus populations and genetic structure been analyzed quantitatively. The subject of this review is the analysis of genetic variation, its quantification in plant virus populations, and what factors and processes determine the genetic structure of these populations and its temporal change. The high potential for genetic variation in plant viruses, through either mutation or genetic exchange by recombination or reassortment of genomic segments, need not necessarily result in high diversity of virus populations. Selection by factors such as the interaction of the virus with host plants and vectors and random genetic drift may in fact reduce genetic diversity in populations. There is evidence that negative selection results in virus-encoded proteins being not more variable than those of their hosts and vectors. Evidence suggests that small population diversity, and genetic stability, is the rule. Populations of plant viruses often consist of a few genetic variants and many infrequent variants. Their distribution may provide evidence of a population that is undifferentiated, differentiated by factors such as location, host plant, or time, or that fluctuates randomly in composition, depending on the virus.

Notes: Abstract The vast evolutionary gulf between plants and animals-in terms of structure, composition, and many environmental factors-would seem to preclude the possibility that these organisms could act as receptive hosts to the same microorganism. However, some pathogens are capable of establishing themselves and thriving in members of both the plant and animal kingdoms. The identification of functionally conserved virulence mechanisms required to infect hosts of divergent evolutionary origins demonstrates the remarkable conservation in some of the underlying virulence mechanisms of pathogenesis and is changing researchers' thinking about the evolution of microbial pathogenesis.

Notes: Abstract Polygalacturonase-inhibiting proteins (PGIPs) are extracellular plant proteins capable of inhibiting fungal endopolygalacturonases (PGs). Plants have evolved different PGIPs with specific recognition abilities against the many PGs produced by fungi. The genes encoding PGIPs are organized into families, and different members of each family may encode proteins with nearly identical characteristics but different specificities and regulation. PGIPs are typically induced by pathogen infection and stress-related signals. The recognition ability of PGIPs resides in their LRR (leucine-rich repeat) structure, where solvent-exposed residues in the beta-strand/beta-turn motifs of the LRRs are determinants of specificity. Manipulation of the primary structure of PGIPs is expected to generate more efficient PGIPs with novel recognition specificities to protect crop plants against pathogens.

Notes: Abstract This article summarizes studies of viral coat (capsid) proteins (CPs) of RNA plant viruses. In addition, we discuss and seek to interpret the knowledge accumulated to date. CPs are named for their primary function; to encapsidate viral genomic nucleic acids. However, encapsidation is only one feature of an extremely diverse array of structural, functional, and ecological roles played during viral infection and spread. Herein, we consider the evolution of viral CPs and their multitude of interactions with factors encoded by the virus, host plant, or viral vector (biological transmission agent) that influence the infection and epidemiological facets of plant disease. In addition, applications of today's understanding of CPs in the protection of crops from viral infection and use in the manufacture of valuable compounds are considered.

Notes: Most of us want to be successful in what we do-either financially or programmatically. For me, being a good, well-respected plant pathologist is what motivated me throughout my professional career. After being trained as a plant pathologist at the University of California-Davis, an institution that prides itself in solving problems, I spent the majority of my career in population-sparse Montana-"the last best place." And best place it has been for me as I became involved in researching a number of plant disease problems and solving a few. J.C. Walker's philosophy of keeping "one foot in the furrow" has stood by me, and I encourage young plant pathologists to adopt it as well to ensure a productive and satisfying life in agricultural science.

Notes: Abstract Historically, the study of plant viruses has contributed greatly to the elucidation of eukaryotic biology. Recently, concurrent with the development of viruses into expression vectors, the biotechnology industry has developed an increasing number of disease therapies utilizing recombinant proteins. Plant virus vectors are viewed as a viable option for recombinant protein production. Employing pathogens in the process of creating added value to agriculture is, in effect, making an ally from an enemy. This review discusses the development and use of viruses as expression vectors, with special emphasis on (+) strand RNA virus systems. Further, the use of virus expression vectors in large-scale agricultural settings to produce recombinant proteins is described, and the technical challenges that need to be addressed by agriculturists and molecular virologists to fully realize the potential of this latest evolution of plant science are outlined.

Notes: Abstract The feeding sites induced by sedentary root-endoparasitic nematodes have long fascinated researchers. Nematode feeding sites are constructed from plant cells, modified by the nematode to feed itself. Powerful new techniques are allowing us to begin to elucidate the molecular mechanisms that produce the ultrastructural features in nematode feeding cells. Many plant genes that are expressed in feeding sites produced by different nematodes have been identified in several plant species. Nematode-responsive plant genes can now be grouped in categories related to plant developmental pathways and their roles in the making of a feeding site can be illuminated. The black box of how nematodes bring about such elaborate cell differentiation in the plant is also starting to open. Although the information is far from complete, the groundwork is set so that the functions of the plant and nematode genes in feeding site development can begin to be assessed.

Notes: Abstract Host-selective toxins, a group of structurally complex and chemically diverse metabolites produced by plant pathogenic strains of certain fungal species, function as essential determinants of pathogenicity or virulence. Investigations into the molecular and biochemical responses to these disease determinants reveal responses typically associated with host defense and incompatibility induced by avirulence determinants. The characteristic responses that unify these disparate disease phenotypes are numerous, yet the evidence implicating a causal relationship of these responses, whether induced by host-selective toxins or avirulence factors, in determining the consequences of the host-pathogen interaction is equivocal. This review summarizes some examples of the action of host-selective toxins to illustrate the similarity in responses with those to avirulence determinants.

Notes: Abstract Antibiotics have been used since the 1950s to control certain bacterial diseases of high-value fruit, vegetable, and ornamental plants. Today, the antibiotics most commonly used on plants are oxytetracycline and streptomycin. In the USA, antibiotics applied to plants account for less than 0.5% of total antibiotic use. Resistance of plant pathogens to oxytetracycline is rare, but the emergence of streptomycin-resistant strains of Erwinia amylovora, Pseudomonas spp., and Xanthomonas campestris has impeded the control of several important diseases. A fraction of streptomycin-resistance genes in plant-associated bacteria are similar to those found in bacteria isolated from humans, animals, and soil, and are associated with transfer-proficient elements. However, the most common vehicles of streptomycin-resistance genes in human and plant pathogens are genetically distinct. Nonetheless, the role of antibiotic use on plants in the antibiotic-resistance crisis in human medicine is the subject of debate.

Notes: Abstract The usefulness of mixtures (multiline cultivars and cultivar mixtures) for disease management has been well demonstrated for rusts and powdery mildews of small grain crops. Such mixtures are more useful under some epidemiological conditions than under others, and experimental methodology, especially problems of scale, may be crucial in evaluating the potential efficacy of mixtures on disease. There are now examples of mixtures providing both low and high degrees of disease control for a wide range of pathosystems, including crops with large plants, and pathogens that demonstrate low host specificity, or are splash dispersed, soilborne, or insect vectored. Though most analyses of pathogen evolution in mixtures consider static costs of virulence to be the main mechanism countering selection for pathogen complexity, many other potential mechanisms need to be investigated. Agronomic and marketing considerations must be carefully evaluated when implementing mixture approaches to crop management. Practical difficulties associated with mixtures have often been overestimated, however, and mixtures will likely play an increasingly important role as we develop more sustainable agricultural systems.

Notes: During my career in Plant Pathology/Nematology, many major advancements have occurred in the study of nematodes-even with their being largely soilborne and thus often overlooked. These biotrophic organisms include the most widespread and important group of plant pathogens-the root-knot nematodes Meloidogyne species-which attack most major crops, as well as thousands of non-crop plant species. Landmark achievements that catalyzed research on these organisms included the discovery of effective nematicides, ectoparasitic forms, elucidation of disease complexes, nematodes as virus vectors, development of host resistance, and new technologies for research. Evolving research thrusts involve interfacing traditional and molecular systematics/diagnostics, adoption of the Caenorhabditis elegans-molecular genetics resource for general nematological research, focus on genetics of parasitism, use of molecular tools in developing host resistance, ecological and quantitative facets, and soil-biology-ecology based integrated management. Educational and international programs are encountering many changes and challenges, as is support for nematology in general.

Notes: Infection of maize kernels by toxigenic fungi remains a challenging problem despite decades of research progress. Cultural practices, including crop rotation, tillage, planting date, and management of irrigation and fertilization, have limited effects on infection and subsequent mycotoxin accumulation. Current infrastructure and grain storage practices in developed countries can prevent postharvest development of mycotoxins, but this aspect remains a threat in developing countries, especially in tropical areas. Because most mycotoxin problems develop in the field, strategies are needed to prevent infection of growing plants by toxigenic fungi. Developing genetic resistance to Aspergillus flavus, Gibberella zeae, and Fusarium spp. (particularly F. verticillioides) in maize is a high priority. Sources of resistance to each of these pathogens have been identified and have been incorporated into public and private breeding programs. However, few, if any, commercial cultivars have adequate levels of resistance. Efforts to control infection or mycotoxin development through conventional breeding and genetic engineering are reviewed. The role of transgenic insect control in the prevention of mycotoxins in maize is discussed.

Notes: The Pto gene in tomato confers gene-for-gene resistance to Pseudomonas syringae pv. tomato, the causative agent of bacterial speck disease. Pto was first introgressed from a wild species of tomato into cultivated tomato varieties over 60 years ago and is now widely used to control speck disease. Cloning of the Pto gene revealed that it encodes a cytoplasmically localized serine-threonine protein kinase. The molecular basis of gene-for-gene recognition in this pathosystem is the direct physical interaction of the Pto kinase with either of two Pseudomonas effector proteins, AvrPto and AvrPtoB. Upon recognition of AvrPto or AvrPtoB, the Pto kinase acts in concert with Prf, a leucine-rich repeat-containing protein, to activate multiple signal transduction pathways. There has been much progress in understanding the evolutionary origin of the Pto gene, structural details about how the Pto kinase interacts with AvrPto and AvrPtoB, signaling steps downstream of Pto, and defense responses activated by the Pto pathway. Future work on this model system will focus on how the interaction of the Pto kinase with bacterial effector proteins activates signal transduction, defining the specific role of signaling components, and ultimately, determining which host defense responses are most responsible for inhibiting growth of the pathogen and suppressing symptoms of bacterial speck disease.

Notes: Quorum sensing (QS) allows bacteria to assess their local population density and/or physical confinement via the secretion and detection of small, diffusible signal molecules. This review describes how phytopathogenic bacteria have incorporated QS mechanisms into complex regulatory cascades that control genes for pathogenicity and colonization of host surfaces. Traits regulated by QS include the production of extracellular polysaccharides, degradative enzymes, antibiotics, siderophores, and pigments, as well as Hrp protein secretion, Ti plasmid transfer, motility, biofilm formation, and epiphytic fitness. Since QS regulatory systems are often required for pathogenesis, interference with QS signaling may offer a means of controlling bacterial diseases of plants. Several bacterial pathogens of plants that have been intensively studied and have revealed information of both fundamental and practical importance are reviewed here: Agrobacterium tumefaciens, Pantoea stewartii, Erwinia carotovora, Ralstonia solanacearum, Pseudomonas syringae, Pseudomonas aeruginosa, and Xanthomonas campestris.

Notes: Natural and agricultural ecosystems harbor a wide variety of microorganisms that play an integral role in plant health, crop productivity, and preservation of multiple ecosystem functions. Interactions within and among microbial communities are numerous and range from synergistic and mutualistic to antagonistic and parasitic. Antagonistic and parasitic interactions have been exploited in the area of biological control of plant pathogenic microorganisms. To date, biocontrol is typically viewed from the perspective of how antagonists affect pathogens. This review examines the other face of this interaction: how plant pathogens respond to antagonists and how this can affect the efficacy of biocontrol. Just as microbial antagonists utilize a diverse arsenal of mechanisms to dominate interactions with pathogens, pathogens have surprisingly diverse responses to counteract antagonism. These responses include detoxification, repression of biosynthetic genes involved in biocontrol, active efflux of antibiotics, and antibiotic resistance. Understanding pathogen self-defense mechanisms for coping with antagonist assault provides a novel approach to improving the durability of biologically based disease control strategies and has implications for the deployment of transgenes (microorganisms or plants).

Notes: Biotechnology offers sustainable solutions to the problem of plant parasitic nematode control. There are several possible approaches for developing transgenic plants with improved nematode resistance; these include anti-invasion and migration strategies, feeding-cell attenuation, and antinematode feeding and development strategies. The essential elements of an effective control strategy are (a) genes that encode an antinematode effector protein, peptide or interfering RNA and (b) promoters that direct a specific pattern of expression for that effector. This review summarizes information on effectors that act directly against the nematode as well as those aimed at disrupting the nematode feeding site. We discuss patterns of promoter activity that could deliver expression of these effectors in a restricted and directed manner. Societal opposition to the technology of GM-nematode control is also discussed.

Notes: An increasing interest has emerged with respect to the importance of microbial diversity in soil habitats. The extent of the diversity of microorganisms in soil is seen to be critical to the maintenance of soil health and quality, as a wide range of microorganisms is involved in important soil functions. This review focuses on recent data relating how plant type, soil type, and soil management regime affect the microbial diversity of soil and the implication for the soil's disease suppressiveness. The two main drivers of soil microbial community structure, i.e., plant type and soil type, are thought to exert their function in a complex manner. We propose that the fact that in some situations the soil and in others the plant type is the key factor determining soil microbial diversity is related to the complexity of the microbial interactions in soil, including interactions between microorganisms and soil and microorganisms and plants. A conceptual framework, based on the relative strengths of the shaping forces exerted by plant and soil versus the ecological behavior of microorganisms, is proposed.

Notes: Fusarium head blight (FHB) is a devastating disease of wheat and barley worldwide. Resistant cultivars could reduce damage from FHB. Chinese wheat cultivar Sumai 3 and its derivatives represent the greatest degree of resistance to FHB known. A major quantitative trait locus (QTL) on chromosome 3BS and other minor QTL for FHB resistance have been identified in these cultivars and used in wheat-breeding programs worldwide. Many breeding lines with the 3BS resistance QTL and improved agronomic traits have been developed. In barley, only limited sources of FHB resistance are available, especially in six-rowed barley, and none of them contains a DON level low enough to meet the safety requirement of the brewing industry. Several QTL have been identified for lower FHB severity, DON content, and kernel discoloration and used to enhance FHB resistance in barley. Marker-assisted selection for FHB resistance QTL on 3BS of wheat and on 2H of barley is in progress.

Notes: The xenognostic mechanisms of two multi-host pathogens, the causative agent of crown gall tumors Agrobacterium tumefaciens and the parasitic plant Striga asiatica, are compared. Both organisms are general plant pathogens and require similar information prior to host commitment. Two mechanistic strategies, chemical perception and metabolic complementation, are used to ensure successful host commitment. The critical reactions at host-parasite contact are proton and electron transfer events. Such strategies may be common among multi-host pathogens.

Notes: Identification of the biological properties contributing to the function of suppressive soils is a necessary first step to the management of such systems for use in the control of soilborne diseases. The development and application of molecular methods for the characterization and monitoring of soil microbial properties will enable a more rapid and detailed assessment of the biological nature of soil suppressiveness. Although suppressive soils have provided a wealth of microbial resources that have subsequently been applied for the biological control of soilborne plant pathogens, the full functional capabilities of the phenomena have not been realized in production agricultural ecosystems. Cultural practices, such as the application of soil amendments, have the capacity to enhance disease suppression, though the biological modes of action may vary from that initially resident to the soil. Plants have a distinct impact on characteristics and activity of resident soil microbial communities, and therefore play an important role in determining the development of the disease-suppressive state. Likewise, plant genotype will modulate these same biological communities, and should be considered when developing strategies to exploit the potential of such a natural disease control system. Implementation of consistently effective practices to manage this resource in an economically and environmentally feasible manner will require more detailed investigation of these biologically complex systems and refinement of currently available methodologies.

Notes: Systemic acquired resistance (SAR) is a mechanism of induced defense that confers long-lasting protection against a broad spectrum of microorganisms. SAR requires the signal molecule salicylic acid (SA) and is associated with accumulation of pathogenesis-related proteins, which are thought to contribute to resistance. Much progress has been made recently in elucidating the mechanism of SAR. Using the model plant Arabidopsis, it was discovered that the isochorismate pathway is the major source of SA during SAR. In response to SA, the positive regulator protein NPR1 moves to the nucleus where it interacts with TGA transcription factors to induce defense gene expression, thus activating SAR. Exciting new data suggest that the mobile signal for SAR might be a lipid molecule. We discuss the molecular and genetic data that have contributed to our understanding of SAR and present a model describing the sequence of events leading from initial infection to the induction of defense genes.

Notes: Xylella fastidiosa 9a5c (XF-9a5c) and Xanthomonas axonopodis pv. citri (XAC) are bacteria that infect citrus plants. Sequencing of the genomes of these strains is complete and comparative analyses are now under way with the genomes of other bacteria of the same genera. In this review, we present an overview of this comparative genomic work. We also present a detailed genomic comparison between XF-9a5a and XAC. Based on this analysis, genes and operons were identified that might be relevant for adaptation to citrus. XAC has two copies of a type II secretion system, a large number of cell wall-degrading enzymes and sugar transporters, a complete energy metabolism, a whole set of avirulence genes associated with a type III secretion system, and a complete flagellar and chemotatic system. By contrast, XF-9a5c possesses more genes involved with type IV pili biosynthesis than does XAC, contains genes encoding for production of colicins, and has 4 copies of Type I restriction/modification system while XAC has only one.

Notes: Most hypovirulence in the chestnut blight fungus, Cryphonectria parasitica, is associated with infection by fungal viruses in the family Hypoviridae. Hypovirulence has controlled chestnut blight well in some locations in Europe and in Michigan in the United States. In contrast, with few exceptions, biological control has failed almost completely in eastern North America. Therapeutic treatment of individual cankers is successful in most cases, but the success of hypovirulence at the population level depends on the natural spread of viruses. Characteristics of three interacting trophic levels (virus, fungus, and tree), plus the environment, determine the success or failure of hypovirulence. Vegetative incompatibility restricts virus transmission, but this factor alone is a poor predictor of biological control. Any factor reducing the rate of chestnut blight epidemics enhances hypovirus invasion. Overall, however, not enough is understood about the epidemiological dynamics of this system to determine the crucial factors regulating the establishment of hypovirulence in chestnut forests.

Notes: Disease diagnosis is based on a number of factors, including laboratory tests for pathogen identification. Rapid development of genomic techniques for characterization of bacteria over the past decade has greatly simplified and improved pathogen detection and identification, but DNA-based methods have not yet entirely replaced traditional culture and phenotypic tests in the plant industry. The first section of this review focuses on rapid immunodiagnostic and DNA-based detection methods for known bacterial pathogens in plants or plant products, which often manifest no symptoms of disease. The second section covers the broader topic of disease diagnosis and new methods for identifying and characterizing bacteria.

Notes: Abstract In light of the well-documented health benefits of physical activity and the fact that the majority of adult men and women are inactive, promoting regular physical activity is a public health priority. This chapter reviews current research findings regarding the determinants of exercise behavior. It also discusses the implications of this knowledge for individual and public health recommendations and intervention strategies for promoting physical activity. The discussion is predicated on the belief that physical activity is a complex, dynamic process. During their lives, individuals typically move through various phases of exercise participation that are determined by diverse factors. This chapter discusses physical activity determinants in two broad categories: individual characteristics, including motivations, self-efficacy, exercise history, skills, and other health behaviors; and environmental characteristics such as access, cost, and time barriers and social and cultural supports.

Notes: Abstract The relative stability of body weight over the long term and under a variety of environmental conditions that alter short-term energy intake and expenditure provides strong evidence for the regulation of body energy content. The lipostatic theory of energy balance regulation proposed 40 years ago that circulating factors, generated in proportion to body fat stores, acted as signals to the brain, eliciting changes in energy intake and expenditure. The discovery of leptin and its receptors has now provided a molecular basis for this theory. Leptin functions as much more than an adipocyte-derived signal of lipid stores, however. Although suppression of food intake is an important centrally mediated effect of leptin, considerable evidence indicates that leptin also functions both directly and indirectly, via the brain, to orchestrate complex metabolic changes in a number of organs and tissues, altering nutrient flux to favor energy expenditure over energy storage.

Notes: Abstract One of the most often studied associations in epidemiology is dietary fat and breast cancer risk. That migrants from low-risk countries increase their risk on immigrating to higher-risk countries suggests that some modifiable lifestyle or environmental factor is responsible for the development of breast cancer. Although early international correlational studies and experimental animals studies support dietary fat as a risk factor for breast cancer, more recent data from case-control studies and cohort studies have been equivocal, thus the analytical data do not support a strong positive association. The conflicting results from analytic studies may be due to methodologic issues associated with study design, dietary assessment tools, measurement error, improper statistical analyses, and a lack of heterogeneity in fat intake among the study population. Moreover, current dietary questionnaires may be inadequate in capturing true dietary intakes or capturing the risk with exposure during earlier periods of a woman's life. Although two large clinical trials investigating the fat/breast cancer relationships issue are underway, researchers are generally skeptical at their ability to detect an independent association between fat and breast cancer risk. Further epidemiologic studies using current methodology may not prove to be fruitful in generating definitive answers to shed light on this controversial issue. In addition, rather than concentrating on dietary fat, researchers should focus on diets that are not only low in saturated fat, but also high in fruit and vegetable consumption. Researchers should take advantage of advances in molecular and genetic technology for a different perspective in examining the issue. For example, markers of susceptibility to breast cancer that can detect women at higher risk for breast cancer may be helpful in clarifying the role of dietary fat. More comprehensive and multiple approaches to studying dietary factors and breast cancer are recommended.

Notes: Abstract Apolipoprotein (apo)B circulates in two distinct forms, apoB100 and apoB48. Human liver secretes apoB100, the product of a large mRNA encoding 4536 residues. The small intestine of all mammals secretes apoB48, which arises following C-to-U deamination of a single cytidine base in the nuclear apoB transcript, introducing a translational stop codon. This process, referred to as apoB RNA editing, operates through a multicomponent enzyme complex that contains a single catalytic subunit, apobec-1, in addition to other protein factors that have yet to be cloned. ApoB RNA editing also exhibits stringent cis-acting requirements that include both structural and sequence-specific elements-specifically efficiency elements that flank the minimal cassette, an AU-rich RNA context, and an 11-nucleotide mooring sequence-located in proximity to a suitably positioned (usually upstream) cytidine. C-to-U RNA editing may become unconstrained under circumstances where apobec-1 is overexpressed, in which case multiple cytidines in apoB RNA, as well as in other transcripts, undergo C-to-U editing. ApoB RNA editing is eliminated following targeting of apobec-1, establishing that there is no genetic redundancy in this function. Under physiological circumstances, apoB RNA editing exhibits developmental, hormonal, and nutritional regulation, in some cases related to transcriptional regulation of apobec-1 mRNA. ApoB and the microsomal triglyceride transfer protein (MTP) are essential for the assembly and secretion of apoB-containing lipoproteins. MTP functions by transferring lipid to apoB during its translation and by transporting triglycerides into the endoplasmic reticulum to form apoB-free lipid droplets. These droplets fuse with nascent apoB-containing particles to form mature, very low-density lipoproteins or chylomicrons. In cultured hepatic cells, lipid availability dictates the rate of apoB production. Unlipidated or underlipidated forms of apoB are subjected to presecretory degradation, a process mediated by retrograde transport from the lumen of the endoplasmic reticulum to the cytosol, coupled with multiubquitination and proteasomal degradation. Although control of lipid secretion in vivo is primarily achieved at the level of lipoprotein particle size, regulation of apoB production by presecretory degradation may be relevant in some dyslipidemic states.

Notes: Abstract Plants consumed by humans contain thousands of phenolic compounds. The effects of dietary polyphenols are of great current interest due to their antioxidative and possible anticarcinogenic activities. A popular belief is that dietary polyphenols are anticarcinogens because they are antioxidants, but direct evidence for this supposition is lacking. This chapter reviews the inhibition of tumorigenesis by phenolic acids and derivatives, tea and catechins, isoflavones and soy preparations, quercetin and other flavonoids, resveratrol, and lignans as well as the mechanisms involved based on studies in vivo and in vitro. Polyphenols may inhibit carcinogenesis by affecting the molecular events in the initiation, promotion, and progression stages. Isoflavones and lignans may influence tumor formation by affecting estrogen-related activities. The bioavailability of the dietary polyphenols is discussed extensively, because the tissue levels of the effective compounds determine the biological activity. Understanding the bioavailability and blood and tissue levels of polyphenols is also important in extrapolating results from studies in cell lines to animal models and humans. Epidemiological studies concerning polyphenol consumption and human cancer risk suggest the protective effects of certain food items and polyphenols, but more studies are needed for clear-cut conclusions. Perspectives on the application of dietary polyphenols for the prevention of human cancer and possible concerns on the consumption of excessive amounts of polyphenols are discussed.

Notes: Abstract Nitric oxide (NO) is synthesized from L-arginine by NO synthase (NOS). As an endothelium-derived relaxing factor, a mediator of immune responses, a neurotransmitter, a cytotoxic free radical, and a signaling molecule, NO plays crucial roles in virtually every cellular and organ function in the body. The discovery of NO synthesis has unified traditionally diverse research areas in nutrition, physiology, immunology, pathology, and neuroscience. Increasing evidence over the past decade shows that many dietary factors, including protein, amino acids, glucose, fructose, cholesterol, fatty acids, vitamins, minerals, phytoestrogens, ethanol, and polyphenols, are either beneficial to health or contribute to the pathogenesis of chronic diseases partially through modulation of NO production by inducible NOS or constitutive NOS. Although most published studies have focused on only a single nutrient and have generated new and exciting knowledge, future studies are necessary to investigate the interactions of dietary factors on NO synthesis and to define the underlying molecular mechanisms.

Notes: Abstract The urea cycle is comprised of five enzymes but also requires other enzymes and mitochondrial amino acid transporters to function fully. The complete urea cycle is expressed in liver and to a small degree also in enterocytes. However, highly regulated expression of several enzymes present in the urea cycle occurs also in many other tissues, where these enzymes are involved in synthesis of nitric oxide, polyamines, proline and glutamate. Glucagon, insulin, and glucocorticoids are major regulators of the expression of urea cycle enzymes in liver. In contrast, the "urea cycle" enzymes in nonhepatic cells are regulated by a wide range of pro- and antiinflammatory cytokines and other agents. Regulation of these enzymes is largely transcriptional in virtually all cell types. This review emphasizes recent information regarding roles and regulation of urea cycle and arginine metabolic enzymes in liver and other cell types.

Notes: Abstract This paper is an attempt to discuss the problem of malnutrition within the framework of the global need for development and the challenges posed by the trends of neoliberalism and globalization. We argue that there is a two-way link between poverty and health in which nutrition plays an important role both as an active and as a mediating factor. Key concepts are exposed and expanded: (a) Development per se does not ensure better health; (b) unequal distribution of income has an independent effect on health indicators after adjusting for total income; (c) improving health can make an important contribution to reducing poverty; (d ) improving nutrition throughout the whole life course is an indispensable strategy for better health; (e) obesity has to be included amongst the most critical health problems, has different traits, and presents with different challenges in the developing world and in the industrialized countries.

Notes: Abstract Humans and other mammals are colonized by a vast, complex, and dynamic consortium of microorganisms. One evolutionary driving force for maintaining this metabolically active microbial society is to salvage energy from nutrients, particularly carbohydrates, that are otherwise nondigestible by the host. Much of our understanding of the molecular mechanisms by which members of the intestinal microbiota degrade complex polysaccharides comes from studies of Bacteroides thetaiotaomicron, a prominent and genetically manipulatable component of the normal human and mouse gut. Colonization of germ-free mice with B. thetaiotaomicron has shown how this anaerobe modifies many aspects of intestinal cellular differentiation/gene expression to benefit both host and microbe. These and other studies underscore the importance of understanding precisely how nutrient metabolism serves to establish and sustain symbiotic relationships between mammals and their bacterial partners.

Notes: Abstract The progression of the aging process leads to a decreased margin of homeostatic reserve and a reduced ability to accommodate metabolic challenges, including nutritional stress. Nutritional frailty refers to the disability that occurs in old age owing to rapid, unintentional loss of body weight and loss of lean body mass (sarcopenia). Sarcopenia, a loss of muscle mass and strength, contributes to functional impairment. Weight loss is commonly due to a reduction in food intake; its possible etiology includes a host of physiological and nonphysiological causes. The release of cytokines during chronic disease may also be an important determinant of frailty. In addition to being anorectic, cytokines also contribute to lipolysis, muscle protein breakdown, and nitrogen loss. Whereas the multiple causes of nutritional frailty are not completely understood, clinical interventions for weight loss, sarcopenia, and cytokine alterations have been used with modest success.

Notes: Abstract Since the late 1980s, there has been an explosion of information on the molecular mechanisms and functions of vitamin A. This review focuses on the essential role of vitamin A in female reproduction and embryonic development and the metabolism of vitamin A (retinol) that results in these functions. Evidence strongly supports that in situ-generated all-trans retinoic acid (atRA) is the functional form of vitamin A in female reproduction and embryonic development. This is supported by the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency with atRA, the block in embryonic development that occurs in retinaldehyde dehydrogenase type 2 null mutant mice, and the essential roles of the retinoic acid receptors, at least in embryogenesis. Early studies of embryos from marginally vitamin A-deficient (VAD) pregnant rats revealed a collection of defects called the vitamin A-deficiency syndrome. The manipulation of all-trans retinoic acid (atRA) levels in the diet of VAD female rats undergoing a reproduction cycle has proved to be an important new tool in deciphering the points of atRA function in early embryos and has provided a means to generate large numbers of embryos at later stages of development with the vitamin A-deficiency syndrome. The essentiality of the retinoid receptors in mediating the activity of atRA is exemplified by the many compound null mutant embryos that now recapitulate both the original vitamin A-deficiency syndrome and exhibit a host of new defects, many of which can also be observed in the VAD-atRA-supported rat embryo model and in retinaldehyde dehydrogenase type 2 (RALDH2) mutant mice. A major task for the future is to elucidate the atRA-dependent pathways that are normally operational in vitamin A-sufficient animals and that are perturbed in deficiency, thus leading to the characteristic VAD phenotypes described above.

Notes: Abstract Phytosterols are cholesterol-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. They are absorbed only in trace amounts but inhibit the absorption of intestinal cholesterol including recirculating endogenous biliary cholesterol, a key step in cholesterol elimination. Natural dietary intake varies from about 167-437 mg/day. Attempts to measure biological effects in feeding studies have been impeded by limited solubility in both water and fat. Esterification of phytosterols with long-chain fatty acids increases fat solubility by 10-fold and allows delivery of several grams daily in fatty foods such as margarine. A dose of 2 g/day as the ester reduces low density lipoprotein cholesterol by 10%, and little difference is observed between Delta5-sterols and 5alpha-reduced sterols (stanols). Phytosterols can also be dispersed in water after emulsification with lecithin and reduce cholesterol absorption when added to nonfat foods. In contrast to these supplementation studies, much less is known about the effect of low phytosterol levels in the natural diet. However, reduction of cholesterol absorption can be measured at a dose of only 150 mg during otherwise sterol-free test meals, suggesting that natural food phytosterols may be clinically important. Current literature suggests that phytosterols are safe when added to the diet, and measured absorption and plasma levels are very small. Increasing the aggregate amount of phytosterols consumed in a variety of foods may be an important way of reducing population cholesterol levels and preventing coronary heart disease.

Notes: Abstract Selenium is an essential trace element that is incorporated into proteins as selenocysteine (Sec), the twenty-first amino acid. Sec is encoded by a UGA codon in the selenoprotein mRNA. The decoding of UGA as Sec requires the reprogramming of translation because UGA is normally read as a stop codon. The translation of selenoprotein mRNAs requires cis-acting sequences in the mRNA and novel trans-acting factors dedicated to Sec incorporation. Selenoprotein synthesis in vivo is highly selenium-dependent, and there is a hierarchy of selenoprotein expression in mammals when selenium is limiting. This review describes emerging themes from studies on the mechanism, kinetics, and efficiency of Sec insertion in prokaryotes. Recent developments that provide mechanistic insight into how the eukaryotic ribosome distinguishes between UGA/Sec and UGA/stop codons are discussed. The efficiency and regulation of mammalian selenoprotein synthesis are considered in the context of current models for Sec insertion.

Notes: Abstract An evolutionary perspective is used to elucidate the etiology of the current epidemic of type 2 diabetes estimated at 151 million people. Our primate legacy, fossil hominid, and hunting-gathering lifestyles selected for adaptive metabolically thrifty genotypes and phenotypes are rendered deleterious through modern lifestyles that increase energy input and reduce output. The processes of modernization or globalization include the availability and abundance of calorically dense/low-fiber/high-glycemic foods and the adoption of sedentary Western lifestyles, leading to obesity among both children and adults in developed and developing countries. These trends are projected to continue for a number of decades.

Notes: The discovery of the function of the receptor for the ecotropic retrovirus as a membrane transporter for the essential amino acids lysine and arginine was a landmark finding in the field of molecular nutrition. This finding indicated that cationic amino acid transporters (CATs) act pathologically as viral receptors. The importance of this transporter was further supported by knockout mice that were not viable after birth. CAT-1 was the first amino acid transporter to be cloned; several other CATs were later characterized biochemically and molecularly. These transporters mediate the bidirectional transport of cationic amino acids, thus supporting important metabolic functions, such as synthesis of proteins, nitric oxide (NO) synthesis, polyamine biosynthesis, and interorgan amino acid flow. This review briefly describes the advances in the regulation of cationic amino acid transport, focusing on the molecular mechanisms that regulate the CAT-1 transporter. Of particular interest to this review is the regulation of CAT-1 by nutritional stresses, such as amino acid availability. The studies that are reviewed conclude that the CAT-1 gene is essential for cell survival during stress because it allows cells to resume growth as soon as amino acids become available.

Notes: Alcohol metabolism takes place primarily in the liver. Initial exposures to ethanol have a major impact on the hepatic redox state and intermediary metabolism as a consequence of ethanol metabolism via alcohol dehydrogenase. However, upon continued exposure to ethanol, the progression of liver injury involves ethanol metabolism via CYP2E1 and consequent oxidant stress, as well as potential direct effects of ethanol on membrane proteins that are independent of ethanol metabolism. Multiple organ systems contribute to liver injury, including the innate immune system and adipose tissue. In response to ethanol exposure, specific signal transduction pathways, including NFkappaB and the mitogen-activated protein kinase family members ERK1/2, JNK, and p38, are activated. These complex responses to ethanol exposure translate into activation of nuclear transcription factors and altered gene expression within the liver, leading to the development of steatosis and inflammation in the early stages of alcohol-induced liver injury.

Notes: Pernicious anemia is a common cause of megaloblastic anemia throughout the world and especially in persons of European or African descent. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia. The breast-fed infant of a vitamin B12-deficient mother is at risk for severe developmental abnormalities, growth failure, and anemia. Elevated methylmalonic acid and/or total homocysteine are sensitive indicators of vitamin B12-deficient diets and correlate with clinical abnormalities. Dietary vitamin B12 deficiency is a severe problem in the Indian subcontinent, Mexico, Central and South America, and selected areas in Africa. Dietary vitamin B12 deficiency is not prevalent in Asia, except in vegetarians. Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae.

Notes: Tissue concentrations of both homocysteine (Hcy) and cysteine (Cys) are maintained at low levels by regulated production and efficient removal of these thiols. The regulation of the metabolism of methionine and Cys is discussed from the standpoint of maintaining low levels of Hcy and Cys while, at the same time, ensuring an adequate supply of these thiols for their essential functions. S-Adenosylmethionine coordinately regulates the flux through remethylation and transsulfuration, and glycine N-methyltransferase regulates flux through transmethylation and hence the S-adenosylmethionine/S-adenosylhomocysteine ratio. Cystathionine beta-synthase activity is also regulated in response to the redox environment, and transcription of the gene is hormonally regulated in response to fuel supply (insulin, glucagon, and glucocorticoids). The H2S-producing capacity of cystathionine gamma-lyase may be regulated in response to nitric oxide. Cys is substrate for a variety of anabolic and catabolic enzymes. Its concentration is regulated primarily by hepatic Cys dioxygenase; the level of Cys dioxygenase is upregulated in a Cys-responsive manner via a decrease in the rate of polyubiquitination and, hence, degradation by the 26S proteasome.

Notes: Erythropoiesis is the process in which new erythrocytes are produced. These new erythrocytes replace the oldest erythrocytes (normally about one percent) that are phagocytosed and destroyed each day. Folate, vitamin B12, and iron have crucial roles in erythropoiesis. Erythroblasts require folate and vitamin B12 for proliferation during their differentiation. Deficiency of folate or vitamin B12 inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes erythroblast apoptosis, resulting in anemia from ineffective erythropoiesis. Erythroblasts require large amounts of iron for hemoglobin synthesis. Large amounts of iron are recycled daily with hemoglobin breakdown from destroyed old erythrocytes. Many recently identified proteins are involved in absorption, storage, and cellular export of nonheme iron and in erythroblast uptake and utilization of iron. Erythroblast heme levels regulate uptake of iron and globin synthesis such that iron deficiency causes anemia by retarded production rates with smaller, less hemoglobinized erythrocytes.

Notes: Package size, plate shape, lighting, socializing, and variety are only a few of the environmental factors that can influence the consumption volume of food far more than most people realize. Although such environmental factors appear unrelated, they generally influence consumption volume by inhibiting consumption monitoring and by suggesting alternative consumption norms. For researchers, this review suggests that redirecting the focus of investigations to the psychological mechanisms behind consumption will raise the profile and impact of research. For health professionals, this review underscores how small structural changes in personal environments can reduce the unknowing overconsumption of food.

Notes: More than one million Americans were expected to be diagnosed with cancer in 2003 (7a). Compelling experimental, epidemiological, and clinical evidence indicates that many cancers are preventable, especially because diet and nutrition are key factors in the modulation of cancer risk. The road to nutritional intervention in cancer prevention has led to successful trials as well as trials that did not reach their intended endpoints. This chapter reviews four case studies of trials, with two ending in success and two ending in null findings or adverse effects. The goal is to identify lessons learned from all four case studies and from the investigations of the complexities inherent to nutritional intervention trials. Additional insights are presented by the research addressing potential mechanisms underlying the endpoints of human trials. Future progress in nutrition and cancer prevention will require expertise from multidisciplinary teams to develop new knowledge about specific nutrients and dietary modifications within a framework of interaction between animal and human research.

Notes: The concept of systemic photoprotection by dietary means is gaining momentum. Skin is continuously exposed to ultraviolet (UV) radiation, the major cause of skin disorders such as sunburn, photodamage, and nonmelanoma skin cancer. Most of the erythemal annual UV dose is encountered under nonvacation conditions, when no sunscreen is applied. In the absence of topically added compounds, skin protection depends solely on endogenous defense. Micronutrients can act as UV absorbers, as antioxidants, or can modulate signaling pathways elicited upon UV exposure. UV-induced erythema is a suitable parameter to assess photoprotection. Dietary protection is provided by carotenoids, tocopherols, ascorbate, flavonoids, or n-3 fatty acids, contributing to maintenance resistance as part of lifelong protection.

Notes: Thymic atrophy, lymphopenia, and compromised cell- and antibody-mediated responses that cause increased rates of infections of longer duration are the immunological hallmarks of zinc deficiency (ZD) in humans and higher animals. As the deficiency advances, a reprogramming of the immune system occurs, beginning with the activation of the stress axis and chronic production of glucocorticoids that accelerate apoptosis among pre-B and -T cells. This reduces lymphopoiesis and causes atrophy of the thymus. In contrast, myelopoiesis is preserved, thereby providing protection for the first line of immune defense or innate immunity. Changes in gene expression for cytokines, DNA repair enzymes, zinc transporters, signaling molecules, etc., suggest that cells of the immune system are attempting to adapt to the stress of suboptimal zinc. Better understanding of the molecular and cellular changes made in response to inadequate zinc should lead to the development of immunotherapeutic interventions.

Notes: Ascorbic acid synthesis in the pig occurs at mid-pregnancy, but activity of the enzyme l-gulono-gamma-lactone oxidase (GLO) declines thereafter during gestation and remains low when the pig nurses the sow. During late gestation the ascorbic acid concentration in the fetus increases, but serum and liver ascorbic acid concentration in the sow declines without affecting the dam's liver GLO activity. It is presumed that as gestation progresses an increased amount of maternal ascorbic acid is transferred to the fetus and to the mammary gland. Colostrum and milk are rich sources of the vitamin and supply the nursing pig with ascorbic acid. The available data suggest that high amounts of ascorbic acid appear to suppress liver GLO activity in the pig. Upon weaning, when exogenous vitamin C is generally not provided, liver GLO activity and serum ascorbic acid increases. During the initial periods postweaning, some reports have indicated growth benefits of supplemental vitamin C. Body tissues differ in their concentrations of ascorbic acid, but tissues of high metabolic need generally have greater concentrations. The corpus luteum in the female, the testis in the male, and the adrenal glands in all pigs contain greater concentrations of the vitamin. Knockout genes preventing ascorbic acid synthesis in pigs have demonstrated poor skeletal and collagen formation and poor antioxidant protection. Under periods of stress ascorbic acid declines in the adrenal, but the pig rapidly recovers to its resting state once the stressor agent is removed. Although there are periods when supplemental vitamin C has been shown to promote pig performance (e.g., during high environmental stress and early postweaning), supplemental vitamin C has not been shown to routinely enhance pig performance.

Notes: Fatty acid desaturases introduce a double bond in a specific position of long-chain fatty acids, and are conserved across kingdoms. Degree of unsaturation of fatty acids affects physical properties of membrane phospholipids and stored triglycerides. In addition, metabolites of polyunsaturated fatty acids are used as signaling molecules in many organisms. Three desaturases, Delta9, Delta6, and Delta5, are present in humans. Delta-9 catalyzes synthesis of monounsaturated fatty acids. Oleic acid, a main product of Delta9 desaturase, is the major fatty acid in mammalian adipose triglycerides, and is also used for phospholipid and cholesteryl ester synthesis. Delta-6 and Delta5 desaturases are required for the synthesis of highly unsaturated fatty acids (HUFAs), which are mainly esterified into phospholipids and contribute to maintaining membrane fluidity. While HUFAs may be required for cold tolerance in plants and fish, the primary role of HUFAs in mammals is cell signaling. Arachidonic acid is required as substrates for eicosanoid synthesis, while docosahexaenoic acid is required in visual and neuronal functions. Desaturases in mammals are regulated at the transcriptional level. Reflecting overlapping functions, three desaturases share a common mechanism of a feedback regulation to maintain products in membrane phospholipids. At the same time, regulation of Delta9 desaturase differs from Delta6 and Delta5 desaturases because its products are incorporated into more diverse lipid groups. Combinations of multiple transcription factors achieve this sophisticated differential regulation.

Notes: Abstract Vitamin D is a secosteroid that is metabolically activated and degraded through the actions of three cytochrome P450 hydroxylase enzymes. Bioactivation occurs through the sequential actions of cytochromes P450C25 and P450C1, resulting in synthesis of the pleiotropic hormone 1,25-dihydroxyvitamin D (1,25VD), which regulates over 60 genes whose actions include those associated with calcium homeostasis and immune responses as well as cellular growth, differentiation, and apoptosis. Inactivation of 1,25VD occurs by C23/C24 oxidation pathways that are catalyzed by the multifunctional cytochrome P450C24 enzyme. Both P450C1 and P450C24 are highly regulated enzymes whose differential expression is controlled in response to numerous cellular modulatory agents such as parathyroid hormone (PTH), calcitonin, interferon gamma, calcium, phosphorus, and pituitary hormones as well as the secosteroid hormone 1,25VD. Most thoroughly studied at the molecular level are the actions of PTH to upregulate P450C1 gene expression and 1,25VD to induce the expression of P450C24. The regulatory action of PTH is mediated through the protein kinase A pathway and involves the phosphorylation of transcription factors that function at the proximal promoter of the P450C1 gene. The upregulation of P450C24 by 1,25VD has both a rapid nongenomic and a slower genomic component that are functionally linked. The rapid response involves protein kinase C and mitogen-activated protein kinase (MAPK) pathways that direct the phosphorylation of nuclear transcription factors. The slower genomic actions are linked to the binding of 1,25VD to the vitamin D receptor (VDR) and the interaction of the VDR-1,25VD complex with its heterodimer partner retinoid-X-receptor and associated coactivators. The regulatory complex is assembled on vitamin D response elements in the proximal promoter of the P450C24 gene and functions to increase the transcription rate.

Notes: Abstract Biotin is a water-soluble vitamin required by all organisms by virtue of its essential role in carboxylation reactions. Although the metabolism and role of biotin in intermediary metabolism are well established, biotin remains one of the most poorly understood water-soluble vitamins in terms of nutritional requirements and responsiveness to physiological and pharmacological states. Significant advances in the understanding of biotin nutriture have been recently accomplished through the description of the kinetics and regulation of biotin transport and improved methods for biotin status assessment. Additionally, the potential role of biotin in the regulation of gene expression has been strengthened through description of altered gene expression during biotin deficiency and through newly described enzymatic activities of the enzyme biotinidase. Given mounting evidence of suboptimum biotin status, a more complete understanding of these aspects of biotin should lead to a greater appreciation of the ways in which biotin aids in the maintenance of health.

Notes: Abstract Long-chain fatty acids are an important constituent of the diet and they contribute to a multitude of cellular pathways and functions. Uptake of long-chain fatty acids across plasma membranes is the first step in fatty acid utilization, and recent evidence supports an important regulatory role for this process. Although uptake of fatty acids involves two components, passive diffusion through the lipid bilayer and protein-facilitated transfer, the latter component appears to play the major role in mediating uptake by key tissues. Identification of several proteins as fatty acid transporters, and emerging evidence from genetically altered animal models for some of these proteins, has contributed significant insight towards understanding the limiting role of transport in the regulation of fatty acid utilization. We are also beginning to better appreciate how disturbances in fatty acid utilization influence general metabolism and contribute to metabolic pathology.

Notes: Studies utilizing experimental animals, epidemiological approaches, cellular models, and clinical trials all provide evidence that retinoic acid and some of its synthetic derivatives (retinoids) are useful pharmacological agents in cancer therapy and prevention. In this chapter, we first review the current knowledge of retinoic acid receptors (RARs) and their role in mediating the actions of retinoic acid. We then focus on a discussion of RARalpha and acute promyelocytic leukemia followed by a discussion of the role of RARs, in particular RARbeta expression, in other cancer types. Loss of normal RAR function in the presence of physiological levels of RA (either due to alterations in the protein structure or level of expression) is associated with a variety of different cancers. In some cases treatment with pharmacological doses of RA can be effective.

Notes: Epidemiological and clinical studies have established that the n-6 fatty acid, linoleic acid (LA), and the n-3 fatty acids, linolenic acid (LNA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) collectively protect against coronary heart disease (CHD). LA is the major dietary fatty acid regulating low-density lipoprotein (LDL)-C metabolism by downregulating LDL-C production and enhancing its clearance. Further, the available mass of LA is a critical factor determining the hyperlipemic effects of other dietary fat components, such as saturated and trans fatty acids, as well as cholesterol. By contrast, n-3 fatty acids, especially EPA and DHA, are potent antiarryhthmic agents. EPA and DHA also improve vascular endothelial function and help lower blood pressure, platelet sensitivity, and the serum triglyceride level. The distinct functions of these two families make the balance between dietary n-6 and n-3 fatty acids an important consideration influencing cardiovascular health. Based on published literature describing practical dietary intakes, we suggest that consumption of ~6% en LA, 0.75% en LNA, and 0.25% en EPA + DHA represents adequate and achievable intakes for most healthy adults. This corresponds to an n-6/n-3 ratio of ~6:1. However, the absolute mass of essential fatty acids consumed, rather than their n-6/n-3 ratio, should be the first consideration when contemplating lifelong dietary habits affecting cardiovascular benefit from their intake.

Notes: Development of bioinformatics tools provided researchers with the ability to identify full sets of trace element-containing proteins in organisms for which complete genomic sequences are available. Recently, independent bioinformatics methods were used to identify all, or almost all, genes encoding selenocysteine-containing proteins in human, mouse, and Drosophila genomes, characterizing entire selenoproteomes in these organisms. It also should be possible to search for entire sets of other trace element-associated proteins, such as metal-containing proteins, although methods for their identification are still in development.

Notes: Cell replication is tightly controlled in normal tissues and aberrant during disease progression, such as in tumorigenesis. The replication of cells can be divided into four distinct phases: Gap 1 (G1), synthesis (S), gap 2 (G2), and mitosis (M). The progression from one phase to the next is intricately regulated and has many "checkpoints" that take into account cellular status and environmental cues. Among the modulators of cell cycle progression are specific nutrients, which function as energy sources or regulate the production and/or function of proteins needed to advance cells through a replicative cycle. In this review, we focus on the roles of specific nutrients (vitamin A, vitamin D, iron, folic acid, vitamin B12, zinc, and glucose) in the control of cell cycle progression and discuss how insights into the mechanisms by which these nutrients modulate this process can be and have been used to control aberrant cell growth in the treatment of prevalent pathologies.

Notes: Abstract During the twentieth century disease detectives progressed by jagged leaps in understanding patterns of plant disease. With ladders, airplanes, and automatic traps they observed airborne spores, and with meteorological theory they explained takeoff, flight, and landing. They analyzed the grand, logistic rise of epidemics and the roles of horizontal versus vertical resistance. From early experiments on the details of life cycles and weather, they simulated epidemics with new computers. Early in the century they revealed genetic diversity with differential varieties and late in the century with differential fungicides and DNA. They learned the interplay of pest, photosynthesis, and supply and demand to reckon loss. Integrating observations of pest, host, losses, and weather, they placed winning short-term bets for farmer and environment on whether to spray. In the twenty-first century, their goal can be analyses so sound that the world can securely place winning long-term bets.

Notes: Abstract Several economically important diseases of unknown or recently determined cause are reviewed. Citrus blight (CB), first described over 100 years ago, was shown in 1984 to be transmitted by root-graft inoculations; the cause remains unknown and is controversial. Based on graft transmission, it is considered to be an infectious agent by some; others suggest that the cause of CB is abiotic. Citrus variegated chlorosis, although probably long present in Argentina, where it was considered to be a variant of CB, was identified as a specific disease and shown to be caused by a strain of Xylella fastidiosa after if reached epidemic levels in Brazil in 1987. Citrus psorosis, described in 1933 as the first virus disease of citrus, is perhaps one of the last to be characterized. In 1988, it was shown to be caused by a very unusual virus. The cause of lettuce big vein appears to be a viruslike agent that is transmitted by a soilborne fungus. Double-stranded RNAs were associated with the disease, suggesting it may be caused by an unidentified RNA virus. Rio Grande gummosis, dry rot root, peach tree short life, and some replant diseases may be diseases of complex etiology. Various microorganisms have been isolated from trees with these diseases, but the diseases may be attributable in part to environmental factors. Determination of the cause of these diseases of complex etiology has proven difficult, in part, because they affect only mature trees.

Notes: Abstract Ralstonia solanacearum causes a lethal bacterial wilt disease of diverse plants. It invades the xylem vessels of roots and disseminates into the stem where it multiplies and wilts by excessive exopolysaccharide production. Many of its key extracytoplasmic virulence and pathogenicity factors are transcriptionally controlled by an extensive network of distinct, interacting signal transduction pathways. The core of this sensory network is the five-gene Phc system that regulates exopolysaccharide, cell-wall-degrading exoenzymes, and other factors in response to a self-produced signal molecule that monitors the pathogen's growth status and environment. Four additional environmentally responsive two-component systems work independently and with the Phc system to fine-tune virulence gene expression. Another critical system is Prh which transduces plant cell-derived signals through a six-gene cascade to activate deployment of the Type III secretion pathway encoded by the hrp pathogenicity genes. Here I summarize knowledge about the regulated targets, signal transduction mechanisms, and crosstalk between Phc, Prh, and other systems. I also provide insight into why R. solanacearum has evolved such a sophisticated sensory apparatus, and how it functions in disease.

Notes: Abstract Diseases caused by species in the genus Phytophthora are responsible for significant economic losses on a wide range of host plants. Spatial pattern is one of the most characteristic ecological properties of a species, and reflects environmental and genetic heterogeneity and reproductive population growth acting on the processes of reproduction, dispersal, and mortality. Species of Phytophthora can be dispersed either in soil, via surface water movement down rows, from rain splash dispersal, by air, or via movement by humans or invertebrate activity. Dispersal results in patchiness in patterns of disease or inoculum in soil. In this chapter we discuss the mechanisms of dispersal of members of this important genus and describe several methods that can be used to statistically analyze data for which spatial coordinates are known. The methods include testing spatial autocorrelation for binary data or continuous data, semivariograms, and regression models for spatial data. The goal of spatial pattern analysis is to gain an understanding of the mechanisms of dispersal of propagules and to sort out the physical and biological factors that are important for spread of plant pathogens and ultimately, for disease management.

Notes: E.M. Freeman's role in early cereal disease research and the beginning of plant pathology at the University of Minnesota has been overshadowed largely by the enormous prestige of his student, E.C. Stakman. During the first decade of the twentieth century, Freeman was responsible for the transferral from Europe to the United States and the subsequent nurturing of important conceptual and technical developments in the area of cereal disease pathology. Under Freeman's leadership, these ideas would come to shape the direction of plant pathology research at the University of Minnesota for decades to follow.

Notes: Abstract Most apomictic root-knot nematodes (RKN; Meloidogyne spp.) have host ranges that encompass the majority of flowering plants, and M. incognita is possibly the world's most damaging crop pathogen. The ancestors, age, and origins of the polyphagous RKN are obscure, but there is increasing evidence that M. incognita, M. javanica, and M. arenaria are closely related, heterogeneous species with a recent, hybrid (reticulate) origin. If so, they must owe much of their current worldwide distributions to spread by agriculture. Host resistance appears to be generally durable in the field, but laboratory studies suggest that apomixis does not prevent evolution in response to selection by a parasitic bacterium (Pasteuria penetrans) and host resistance. Maintaining general fitness may be the evolutionary priority for most populations of polyphagous RKN, and a wide host range, important in the field but not in the laboratory, may be conserved by apomixis. Several factors may help confer a wide host range, including suppression of host resistance, perhaps as a consequence of the strength of the induced susceptible response. Resistance genes effective against RKN appear not to have resulted from coevolution. Rates of juvenile invasion and/or development are low in many wild and some crop plants, with the result that they are both poor hosts and sustain less damage. Overall, it is suggested that greater coordination, particularly of fundamental research, is required.

Notes: Abstract Yellow rust of barley is an invasive disease that was found in the past 10 years in North America. The causal agent, Puccinia striiformis f. sp. hordei, was introduced into Colombia, South America, from Europe in 1975. It spread to all major barley-producing areas in South America by 1982. In 1988 it was found in Mexico and in 1991 in Texas. Since then it has been found in all major barley-producing areas of the American West. Originally described as race (R) 24, barley yellow rust in North America is now known to be a very heterogeneous population. Resistance has been identified, evaluated, and is being introduced into commercial malting and other barley cultivars. Cultural and chemical controls are effective and available. An integrated approach using general field resistance and other tactics is described for sustainable management of barley yellow rust.

Notes: Abstract This retrospective review deals with the sequence of events and research progress on control of stripe rust of wheat and barley in North America. From the discovery of stripe rust in 1915, it documents the early years of stripe rust research, the 20-year hiatus when stripe rust was not considered important and research was almost nonexistent, the short period in the 1950s when stripe rust became prevalent in the central United States, and the severe epidemics in the West in the 1960s and the associated revival and expansion of research. Finally, it covers 1968 to 2001 when the earlier information was consolidated and combined with results of new research to enable prediction and control of stripe rust, especially in the West.

Notes: The replication of positive-strand RNA viruses is a complex multi-step process involving interactions between the viral genome, virus-encoded replication factors, and host factors. The plant virus brome mosaic virus (BMV) has served as a model for positive-strand RNA virus replication, recombination, and virion assembly. This review addresses recent findings on the identification and characterization of host factors in BMV RNA replication. To date, all characterized host factors facilitate steps that lead to assembly of a functional BMV RNA replication complex. Some of these host factors are required for regulation of viral gene expression. Others are needed to co-regulate BMV RNA translation and recruitment of BMV RNAs from translation to viral RNA replication complexes on the endoplasmic reticulum. Other host factors provide essential lipid modifications in the endoplasmic reticulum membrane or function as molecular chaperones to activate the replication complex. Characterizing the functions of these host factors is revealing basic aspects of virus RNA replication and helping to define the normal functions of these factors in the host.

Notes: Like many other plant RNA viruses, Wheat streak mosaic virus (WSMV) sequence diversity within and among infected plants is low given the large number of virions produced. This may be explained by considering aspects of plant virus life history. Intracellular replication of RNA viruses is predominately linear, not exponential, which means that the rate at which mutations accumulate also is linear. Bottlenecks during systemic movement further limit diversity. Analysis of mixed infections with two WSMV isolates suggests that about four viral genomes participate in systemic invasion of each tiller. Low effective population size increases the role of stochastic processes on dynamics of plant virus population genetics and evolution. Despite low pair-wise diversity among isolates, the number of polymorphic sites within the U.S. population is about the same as between divergent strains or a sister species. Characteristics of polymorphism in the WSMV coat protein gene suggest that most variation appears neutral.

Notes: We used the California Pesticide Use Reports to study use of fungicides, bactericides, fumigants, and selected insecticides, primarily for vegetable, fruit, and nut production in California from 1993 to 2000. There were no obvious trends in decreased use of most compounds used to treat plant disease. However, growers have rapidly adopted recently introduced "conventional" compounds. There is very limited use of microbial biocontrol agents to control plant disease and no indication of an increase. We used case studies to explore the potential of different strategies to reduce pesticide use or risk. There have been reductions in use of organophosphate insecticides, largely by substitution with pyrethroids. Theoretically, replacement of "calendar spray" pesticide programs with "environmentally driven" programs could reduce pesticide use in years with lower disease pressure, but this assumes that the majority of growers currently use a "calendar spray" program and that growers who use less than recommended by an environmentally driven program would not increase their use.

Notes: cAMP regulates morphogenesis and virulence in a wide variety of fungi including the plant pathogens. In saprophytic yeasts such as Saccharomyces cerevisiae, cAMP signaling plays an important role in nutrient sensing. In filamentous saprophytes, the cAMP pathway appears to play an integral role in vegetative growth and sporulation, with possible connections to mating. Infection-related morphogenesis includes sporulation (conidia and teliospores), formation of appressoria, infection hyphae, and sclerotia. Here, we review studies of cAMP signaling in a variety of plant fungal pathogens. The primary fungi to be considered include Ustilago maydis, Magnaporthe grisea, Cryphonectria parasitica, Colletotrichum and Fusarium species, and Erisyphe graminis. We also include related information on Trichoderma species that act as mycoparasites and biocontrol agents of phytopathogenic fungi. We point out similarities in infection mechanisms, conservation of signaling components, as well as instances of cross-talk with other signaling pathways.

Notes: Bacteria associated with plants have been observed frequently to form assemblages referred to as aggregates, microcolonies, symplasmata, or biofilms on leaves and on root surfaces and within intercellular spaces of plant tissues. In a wide range of habitats, biofilms are purported to be microniches of conditions markedly different from those of the ambient environment and drive microbial cells to effect functions not possible alone or outside of biofilms. This review constructs a portrait of how biofilms associated with leaves, roots and within intercellular spaces influence the ecology of the bacteria they harbor and the relationship of bacteria with plants. We also consider how biofilms may enhance airborne dissemination, ubiquity and diversification of plant-associated bacteria and may influence strategies for biological control of plant disease and for assuring food safety. Trapped by a nexus, coordinates uncertain Ever expanding or contracting Cannibalistic and scavenging sorties Excavations through signs of past alliances Consensus signals sound revelry Then time warped by viscosity Genomes showing codependence A virtual microbial beach party With no curfew and no time-out A few estranged cells seeking exit options, Looking for another menagerie. David Sands, Montana State University, Bozeman, February 2003

Notes: Spiroplasma citri, the type species of the genus Spiroplasma (Spiroplasmataceae, Mollicutes), is restricted to the phloem sieve tubes and transmitted by phloem sap-feeding insects, as is characteristic of the phytopathogenic mollicutes. The spiroplasmas are the only mollicutes showing motility and helical morphology, apparently mediated by a contractile fibrillar cytoskeleton bound to the inner surface of the spiroplasmal membrane. MreB genes, which are involved in cell-shape determination, have been identified in S. citri. Identified genes of other functional groups are those involved in the transmission of S. citri by the leafhoppers and genes coding for lipoproteins, including spiralin, bound to the outer surface of the spiroplasma membrane. S. citri mutants that are unable to use fructose induce only mild and delayed symptoms. Fructose utilization by the sieve tube-restricted wild-type spiroplasmas is postulated to deprive the companion cells of fructose, thereby impairing sucrose loading into the sieve tubes.

Notes: There is increasing pressure to reduce the use of pesticides in modern crop production to decrease the environmental impact of current practice and to lower production costs. It is therefore imperative that sprays are only applied when and where needed. Since diseases in fields are frequently patchy, sprays may be applied unnecessarily to disease-free areas. Disease control could be more efficient if disease patches within fields could be identified and spray applied only to the infected areas. Recent developments in optical sensor technology have the potential to enable direct detection of foliar disease under field conditions. This review assesses recent developments in the use of optical methods for detecting foliar disease, evaluates the likely benefits of spatially selective disease control in field crops, and discusses practicalities and limitations of using optical disease detection systems for crop protection in precision pest management.

Notes: Tobacco mosaic virus (TMV) has had an illustrious history for more than 100 years, dating to Beijerinck's description of the mosaic disease of tobacco as a contagium vivum fluidum and the modern usage of the word "virus." Since then, TMV has been acknowledged as a preferred didactic model and a symbolic model to illuminate the essential features that define a virus. TMV additionally emerged as a prototypic model to investigate the biology of host plants, namely tobacco. TMV also exemplifies how a model system furthers novel, and often unexpected, developments in biology and virology. Today, TMV is used as a tool to study host-pathogen interactions and cellular trafficking, and as a technology to express valuable pharmaceutical proteins in tobacco. The history of TMV illustrates how pragmatic strategies to control an economically important disease of tobacco have had unexpected and transforming effects across platforms that impinge on plant health and public health. Tobacco mosaic virus: An RNA virus that causes mosaic disease in tobacco and similar effects in other plants, much used as an experimental subject; abbrev. TMV. (8)

Notes: Abstract Throughout the world, the most common nutritional deficiency disorder of infants is iron deficiency. Developing effective strategies for preventing iron deficiency requires detailed knowledge of iron retention under ordinary living conditions. For the adult population, such knowledge is at an advanced stage, but relatively little is known about infants. Many reports of iron retention by infants have been based on the assumption that, as in normal and iron-deficient adults, 80%-100% of newly absorbed iron is promptly incorporated into circulating erythrocytes, but this assumption is not supported by available data. This communication presents a review of iron retention by term and preterm infants, as determined by metabolic balance studies or 59Fe whole-body counting studies, and it explores the relationship between iron retention and postnatal age, iron nutritional status, iron intake (or dose), and type of feeding.

Notes: Abstract Sustained dynamic exercise stimulates amino acid oxidation, chiefly of the branched-chain amino acids, and ammonia production in proportion to exercise intensity; if the exercise is intense enough, there is a net loss of muscle protein (as a result of decreased protein synthesis, increased breakdown, or both); some of the amino acids are oxidized as fuel, whereas the rest provide substrates for gluconeogenesis and possibly for acid-based regulation. Protein balance is restored after exercise, but no hypertrophy occurs with habitual dynamic exercise. Resistance exercise causes little change in amino acid oxidation but probably depresses protein synthesis and elevates breakdown acutely. After exercise, protein synthesis rebounds for 〈=48 h, but breakdown remains elevated, and net positive balance is achieved only if amino acid availability is increased. There is no evidence that habitual exercise increases protein requirements; indeed protein metabolism may become more efficient as a result of training.

Notes: Abstract Currently, estimates of human zinc requirements depend primarily on a factorial approach. The availability of tracer techniques employing zinc stable isotopes has facilitated the acquisition of data on major variables of zinc homeostasis in addition to those that can be measured with careful metabolic balance techniques. These data have promising potential to facilitate and improve the factorial approach. The thesis proposed in this paper is that realistic estimations of dietary zinc requirements by a factorial approach require attention to the dynamic interrelationships between major variables of zinc homeostasis. This applies especially to the positive relationship between endogenous fecal zinc and total absorbed zinc, which is the essential starting point in estimating physiologic and, from there, dietary requirements.

Notes: Abstract Dietary essential fatty acids are the precursors for eicosanoids. Among the eicosanoids derived from arachidonic acid, prostaglandin (PG) E2 is known to possess immunosuppressive actions. Thus, it has been a prevailing hypothesis that the immuno-modulatory roles of dietary fatty acids are mediated at least in part through the alteration of PG biosynthesis. PGs exert their biological effects through their cognate receptors. There are four subtypes of PGE receptors (EP1, EP2, EP3, and EP4) so far identified. Although the association of EP receptors with G proteins coupled to adenylate cyclase and the mobilization of intracellular calcium are well documented, downstream signaling pathways for these receptors are virtually unknown. Identification of downstream signaling pathways for each subtype of EP receptors and target genes regulated by the activation of the receptor will help with our understanding of the mechanism by which dietary fatty acids affect immune responses through the modulation of PGE2 biosynthesis. Emerging evidence suggests that fatty acids can additionally act as second messengers, regulators of signal transducing molecules or transcription factors. Acylation with long-chain fatty acids can occur on a variety of signaling molecules and can affect their membrane translocation and functions. Dietary fatty acids can alter functional properties of lipid mediators by changing the composition of acyl moieties of these molecules. Evidence accumulated recently indicates that long-chain unsaturated fatty acids and their metabolites bind and activate peroxisome proliferator-activated receptors (PPARs). PPARs are nuclear hormone receptors and transcription factors that regulate the expression of broad arrays of genes involved not only in lipid and glucose metabolism, but also in immune and inflammatory responses. PPARs may therefore be important cellular targets that mediate modulation of immune responses by dietary fatty acids. Together, it becomes clear now that multiple steps in various receptor-mediated signaling pathways can be modulated by dietary fatty acids. It will be a challenging task to quantitatively determine how different fatty acids alter functional properties of multitude of signaling components and final cellular responses. Elucidating the mechanism of actions of fatty acids on receptor-mediated signaling pathways in immuno-competent cells will provide a new insight for understanding the immuno-modulatory roles of dietary fatty acids.

Notes: Abstract The cloning of the G protein-coupled, extracellular calcium (Ca2+o)-sensing receptor (CaR) has identified a central mediator of the mechanism governing systemic Ca2+o homeostasis. This system enables organisms to adapt successfully to wide variations in dietary Ca2+o intake while maintaining near constancy of Ca2+o. Whereas discussions of Ca2+o homeostasis have generally focused on the key role of Ca2+o-elicited changes in parathyroid hormone secretion, the presence of the CaRs in effector tissues of this system enables direct regulation of processes (e.g. renal tubular Ca2+ reabsorption and possibly bone formation and resorption) that add additional layers of homeostatic control. As we understand more about how the CaR regulates these tissues, we may find that it participates in other processes relevant to mineral ion homeostasis, including the control of the 1-hydroxylation and activation of vitamin D3 or reabsorption of phosphate in the renal proximal tubule. Regardless, the remarkable sensitivity of the CaR to small changes in Ca2+o allows adjustments in the response of the Ca2+o homeostatic system to increases or decreases in the intake of dietary Ca2+, for instance, that cause barely detectable alterations in Ca2+o. Furthermore, the CaR likely participates in coordinating interactions among several different homeostatic control systems (including those for water, Mg2+o, Na+, extracellular volume, and/or blood pressure), despite the fact that these systems are often considered to function largely independently of mineral ion metabolism.

Notes: Abstract The microsomal triglyceride transfer protein (MTP) is a dimeric lipid transfer protein consisting of protein disulfide isomerase and a unique 97-kDa subunit. In vitro, MTP accelerates the transport of triglyceride, cholesteryl ester, and phospholipid between membranes. It was recently demonstrated that abetalipoproteinemia, a hereditary disease characterized as an inability to produce chylomicrons and very low-density lipoproteins in the intestine and liver, respectively, results from mutations in the gene encoding the 97-kDa subunit of the microsomal triglyceride transfer protein. Downstream effects resulting from this defect include malnutrition, very low plasma cholesterol and triglyceride levels, altered lipid and protein compositions of membranes and lipoprotein particles, and vitamin deficiencies. Unless treated, abetalipoproteinemic subjects develop gastrointestinal, neurological, ophthalmological, and hematological abnormalities.

Notes: Abstract Research on human milk oligosaccharides (HMOs) has received much attention in recent years. However, it started about a century ago with the observation that oligosaccharides might be growth factors for a so-called bifidus flora in breast-fed infants and extends to the recent finding of cell adhesion molecules in human milk. The latter are involved in inflammatory events recognizing carbohydrate sequences that also can be found in human milk. The similarities between epithelial cell surface carbohydrates and oligosaccharides in human milk strengthen the idea that specific interactions of those oligosaccharides with pathogenic microorganisms do occur preventing the attachment of microbes to epithelial cells. HMOs may act as soluble receptors for different pathogens, thus increasing the resistance of breast-fed infants. However, we need to know more about the metabolism of oligosaccharides in the gastrointestinal tract. How far are oligosaccharides degraded by intestinal enzymes and does oligosaccharide processing (e.g. degradation, synthesis, and elongation of core structures) occur in intestinal epithelial cells? Further research on HMOs is certainly needed to increase our knowledge of infant nutrition as it is affected by complex oligosaccharides.

Notes: Abstract C/EBPs are a family of transcription factors that play important roles in energy metabolism. Although initially thought to be constitutive regulators of transcription, an increasing amount of evidence indicates that their transactivating capacity within the cell can be modulated by nutrients and hormones. There are several mechanisms whereby this occurs. First, hormones/nutrients are known to directly alter the expression of C/EBPs. Second, hormones/nutrients may cause an alteration in the phosphorylation state of C/EBPs, which can affect their DNA-binding activity or transactivating capacity. Third, C/EBPs can function as accessory factors on gene promoters within a hormone response unit, interacting with other transcription factors to enhance the degree of responsiveness to specific hormones. Given their role in regulating genes involved in a wide variety of metabolic events, advancing our understanding of the molecular mechanism of action of C/EBPs will undoubtedly further our appreciation for the role these transcription factors play in both health and disease.

Notes: Abstract Folate catabolism has been assumed to result from the nonenzymatic oxidative degradation of labile folate cofactors. Increased rates of folate catabolism and simultaneous folate deficiency occur in several physiological states, including pregnancy, cancer, and when anticonvulsant drugs are used. These studies have introduced the possibility that folate catabolism may be a regulated cellular process that influences intracellular folate concentrations. Recent studies have demonstrated that the iron storage protein ferritin can catabolize folate in vitro and in vivo, and increased heavy-chain ferritin synthesis decreases intracellular folate concentrations independent of exogenous folate levels in cell culture models. Ferritin levels are elevated in most physiological states associated with increased folate catabolism. Therefore, folate catabolism is emerging as an important component in the regulation of intracellular folate concentrations and whole-body folate status.

Notes: Abstract Nutritionists have long understood that intestinal nematode parasites have deleterious effects on host nutritional status, but only recently has the importance of malnutrition as a predisposing factor to intestinal nematodes been recognized. Here we review experimental and field studies on the effects of protein, energy, zinc, vitamin A, and iron deficiencies on gastrointestinal (GI) nematodes of humans, livestock, and laboratory rodents, and draw certain conclusions about the state of our current understanding. In general, malnutrition promotes the establishment, survival, and fecundity of these parasites, but the magnitude of the effect depends on factors such as host species, parasite species, particular infection protocol used, magnitude of the infection, severity of the nutritional deficiency, and presence of single or multiple infections and single or multiple nutritional deficiencies. We highlight the Th2 arm of the immune system as a component of primary importance in the association between malnutrition and GI nematode infections. We summarize what is known about underlying mechanisms that may account for the observed patterns. Finally, we suggest future research directions.