ALBERT

Notes: Abstract About 40% of patients undergoing maintenance dialysis suffer from varying degrees of protein-energy malnutrition. This is a problem of substantial importance because many measures of nutritional status correlate with the risk of morbidity and mortality. There are many causes of protein-energy malnutrition in maintenance dialysis patients. Evidence indicates that nutritional decline begins even when the reduction in glomerular filtration rate is modest, and it is likely that the observed decrease in dietary protein and energy intake plays an important role. The nutrient intake of patients receiving maintenance dialysis also is often inadequate, and several lines of evidence suggest that toxins that accumulate with renal failure suppress appetite and contribute to nutritional decline once patients are on maintenance dialysis. Recent epidemiologic studies have suggested that both increased serum levels of leptin and inflammation may reduce nutrient intake and contribute to the development of protein-energy malnutrition. It is likely that associated illnesses, which are highly prevalent, contribute to malnutrition in maintenance dialysis patients. Recent data from the United States Renal Data System registry suggest that in the United States, the mortality rate of dialysis patients is improving. However, it remains high. We offer suggestions for predialysis and dialysis care of these patients that can result in improvement in their nutritional status. Whether this improvement will result in a decrease in patient morbidity and mortality is unknown.

Notes: Abstract Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5000 different flavonoids have been described. The six major subclasses of flavonoids include the flavones (e.g., apigenin, luteolin), flavonols (e.g., quercetin, myricetin), flavanones (e.g., naringenin, hesperidin), catechins or flavanols (e.g., epicatechin, gallocatechin), anthocyanidins (e.g., cyanidin, pelargonidin), and isoflavones (e.g., genistein, daidzein). Most of the flavonoids present in plants are attached to sugars (glycosides), although occasionally they are found as aglycones. Interest in the possible health benefits of flavonoids has increased owing to their potent antioxidant and free-radical scavenging activities observed in vitro. There is growing evidence from human feeding studies that the absorption and bioavailability of specific flavonoids is much higher than originally believed. However, epidemiologic studies exploring the role of flavonoids in human health have been inconclusive. Some studies support a protective effect of flavonoid consumption in cardiovascular disease and cancer, other studies demonstrate no effect, and a few studies suggest potential harm. Because there are many biological activities attributed to the flavonoids, some of which could be beneficial or detrimental depending on specific circumstances, further studies in both the laboratory and with populations are warranted.

Notes: Abstract Investigation of the in vivo kinetics of folate metabolism provides information that contributes to a better understanding of the manner in which this vitamin is processed in vivo. Kinetic studies can yield insight into the requirements for folate, especially with respect to factors that may lead to increased requirements. This review considers the strengths and weaknesses of various approaches to the study of folate kinetics and resulting data, followed by a summary and interpretation of existing data.

Notes: Abstract Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor involved in the control of metabolism. Research on PPARgamma is oriented towards understanding its role in insulin sensitization, which was inspired by the discovery that antidiabetic agents, the thiazolidinediones, were agonists for PPARgamma. PPARgamma stimulation improves glucose tolerance and insulin sensitivity in type 2 diabetic patients and in animal models of insulin resistance through mechanisms that are incompletely understood. Upon activation, PPARgamma heterodimerizes with retinoid X receptor, recruits specific cofactors, and binds to responsive DNA elements, thereby stimulating the transcription of target genes. Because PPARgamma is highly enriched in adipose tissue and because of its major role in adipocyte differentiation, it is thought that the effects of PPARgamma in adipose tissue are crucial to explain its role in insulin sensitization, but recent studies have highlighted the contribution of other tissues as well. Although relatively potent for their insulin-sensitizing action, currently marketed PPARgamma activators have some important undesirable side effects. These concerns led to the discovery of new ligands with potent antidiabetic properties but devoid of certain of these side effects. Data from human genetic studies and from PPARgamma heterozygous knockout mice indicate that a reduction in PPARgamma activity could paradoxically improve insulin sensitivity. These findings suggest that modulation of PPARgamma activity by partial agonists or compounds that affect cofactor recruitment might hold promise for the treatment of insulin resistance.

Notes: Abstract Skeletal muscle contains the majority of the body's glycogen stores and a similar amount of readily accessible energy as intramyocellular triglyceride (imTG). While a number of factors have been considered to contribute to the pathogenesis of insulin resistance (IR) in obesity and type 2 diabetes mellitus (DM), this review will focus on the potential role of skeletal muscle triglyceride content. In obesity and type 2 DM, there is an increased content of lipid within and around muscle fibers. Changes in muscle in fuel partitioning of lipid, between oxidation and storage of fat calories, almost certainly contribute to accumulation of imTG and to the pathogenesis of both obesity and type 2 DM. In metabolic health, skeletal muscle physiology is characterized by the capacity to utilize either lipid or carbohydrate fuels, and to effectively transition between these fuels. We will review recent findings that indicate that in type 2 DM and obesity, skeletal muscle manifests inflexibility in the transition between lipid and carbohydrate fuels. This inflexibility in fuel selection by skeletal muscle appears to be related to the accumulation of imTG and is an important aspect of IR of skeletal muscle in obesity and type 2 DM.

Notes: Abstract Different types of lean mice have been produced by genetic manipulation. Leanness can result from deficiency of stored energy or a lack of adipocytes to store the lipid. Mice lacking functional adipocytes are usually insulin resistant and have fatty livers, and elevated circulating triglyceride levels. Insulin resistance may result from the lack of adipocyte hormones (such as leptin) and increased metabolite (such as triglyceride) levels in nonadipose tissue. Mice with depleted adipocyte triglyceride levels typically are insulin sensitive and have normal or low liver and circulating triglycerides. Mechanisms to produce depleted adipocytes include increased energy expenditure by peripheral tissues, peripheral mechanisms to decrease food intake, and altered central regulation of these processes.

Notes: Abstract Ceruloplasmin is a serum ferroxidase that contains greater than 95% of the copper found in plasma. This protein is a member of the multicopper oxidase family, an evolutionarily conserved group of proteins that utilize copper to couple substrate oxidation with the four-electron reduction of oxygen to water. Despite the need for copper in ceruloplasmin function, this protein plays no essential role in the transport or metabolism of this metal. Aceruloplasminemia is a neurodegenerative disease resulting from inherited loss-of-function mutations in the ceruloplasmin gene. Characterization of this disorder revealed a critical physiological role for ceruloplasmin in determining the rate of iron efflux from cells with mobilizable iron stores and has provided new insights into human iron metabolism and nutrition.

Notes: Abstract In humans, the absence of galactose-1-phosphate uridyltransferase (GALT) leads to significant neonatal morbidity and mortality which are dependent on galactose ingestion, as well as long-term complications of primary ovarian failure and cognitive dysfunction, which are diet independent. The creation of a knockout mouse model for GALT deficiency was aimed at providing an organism in which metabolic challenges and gene manipulation could address the enigmatic pathophysiologic questions raised by humans with galactosemia. Instead, the mouse represents a biochemical phenotype without evidence of clinical morbidity. The similarities and differences between mice and humans with galactosemia are explored from metabolite, enzyme, and process points of view. The mouse both produces and oxidizes galactose in a manner similar to humans. It differs in brain accumulation of galactitol. Future directions for exploration of this enigmatic condition are discussed.

Notes: Abstract It has been a little more than 20 years since the first appreciation that the biologically active hormonal form of the secosteroid vitamin D-classically categorized as a regulator of calcium/phosphorous metabolism and bone mineralization-can exert effects on cells of the immune system. Since then a substantial literature has accumulated to suggest that these effects are exerted on multiple immune cell types, are predominantly suppressive at pharmacologic levels, and are potent enough to have true therapeutic potential in the management or prevention of immune-mediated diseases. Less clear at present, however, are the physiological roles played by the vitamin D endocrine system in the regulation of normal and abnormal immune responses. In this review, an appraisal of the current understanding of vitamin D-mediated immune regulation is presented that emphasizes progress towards its clinical application as well as the manner in which emerging models of normal immune function may facilitate a more complete understanding of its physiologic significance.

Notes: Abstract The association of malnutrition with surgical morbidity and mortality is well recognized. The question of whether this relationship is causal or simply an association in sick patients has been hotly debated. The field of nutrition support has grown out of the belief that correcting malnutrition will modify associated risks for poor outcome. It has been easier to substantiate this belief in some clinical situations than in others. The evidence for nutrition support during the perioperative period is reviewed and recommendations are made about where nutrition support is most useful and where it may be counterproductive. Some of the important unanswered questions about perioperative nutrition support are raised.

Notes: Abstract The resin of the Commiphora mukul tree has been used in Ayurvedic medicine for more than 2000 years to treat a variety of ailments. Studies in both animal models and humans have shown that this resin, termed gum guggul, can decrease elevated lipid levels. The stereoisomers E- and Z-guggulsterone have been identified as the active agents in this resin. Recent studies have shown that these compounds are antagonist ligands for the bile acid receptor farnesoid X receptor (FXR), which is an important regulator of cholesterol homeostasis. It is likely that this effect accounts for the hypolipidemic activity of these phytosteroids.

Notes: Abstract Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

Notes: The chapter reviews the historical development and interactions of U.S. agricultural, economic, nutrition, and development policies relating to the creation of the commercial environment of social, economic, technological, and political factors that favor the development of American obesity.

Notes: New insights into mammalian zinc metabolism have been acquired through the identification and characterization of zinc transporters. These proteins all have transmembrane domains, and are encoded by two solute-linked carrier (SLC) gene families: ZnT (SLC30) and Zip (SLC39). There are at least 9 ZnT and 15 Zip transporters in human cells. They appear to have opposite roles in cellular zinc homeostasis. ZnT transporters reduce intracellular zinc availability by promoting zinc efflux from cells or into intracellular vesicles, while Zip transporters increase intracellular zinc availability by promoting extracellular zinc uptake and, perhaps, vesicular zinc release into the cytoplasm. Both the ZnT and Zip transporter families exhibit unique tissue-specific expression, differential responsiveness to dietary zinc deficiency and excess, and differential responsiveness to physiologic stimuli via hormones and cytokines.

Notes: Much of the science underlying nutrition has come from biochemical studies. This certainly is true in our understanding of the metabolism and function of such micronutrient cofactors as vitamins and metal ions. My own interest stems from an early desire to understand the molecular events in an organism and ultimately to know the fate of those nutrients that are needed to maintain life. My training in chemistry, biochemistry, and nutrition was helpful in gaining knowledge about the interface among these disciplines. My interests followed an understandable trail, beginning with those factors that cause plant galls and continuing through carbohydrate metabolism to vitamins. After all, from studying such pentitols as ribitol with Professor Touster at Vanderbilt University through indoctrination with enzymes, vitamins, and coenzymes with Professor Snell at the University of California-Berkeley, it was rational to begin my independent academic life investigating the enzymes that convert a ribityl-containing vitamin, namely riboflavin, to its operational flavocoenzymes. While at Cornell University, I encountered Professor Wright, who shared an interest in biotin. My realization that there was a similar need to determine the metabolism of lipoate followed logically. Interactions with inorganic chemists such as Professor Sigel at Basel University, as well as inorganic chemists at Cornell, led to an interest in metal ions. As summarized in this article, my colleagues and I are pleased to have contributed to both basic knowledge about cofactors and to have utilized much of this information in extensions to applications. Along the way, I have served by teaching, researching, and administrating at the universities that provided my positions in academe, and I have worked to share the load of numerous public and professional duties that are summarized herein. Altogether it has been an enjoyable career to be a nutritional biochemist. I recommend it for those who follow.

Notes: Abstract Plant health management is the science and practice of understanding and overcoming the succession of biotic and abiotic factors that limit plants from achieving their full genetic potential as crops, ornamentals, timber trees, or other uses. Although practiced as long as agriculture itself, as a science-based concept, plant heath management is even younger than integrated pest management (IPM), and includes and builds upon but is not a replacement for IPM. Probably the greatest collection of success stories for plant health management is the number of diseases managed by cleaning up the planting material. The record for root health management is more mixed, with the loss or phase-out of soil fumigants, and practices such as crop rotation and clean tillage being replaced with more intensive cropping and less or no tillage. Perhaps the greatest scientific and technical advances for plant health management have come from the work aimed at management of the pathogens, pests, and other hazards that arrive by air. Flor's work on flax rust, which produced the gene-for-gene model, is possibly the most significant contribution of plant pathology to the life sciences in the twentieth century. Research aimed at the management of foliar pathogens is also the basis for modern theory on epidemiology, population biology, aerobiology, and disease prediction and decision-support systems. Even IPM arose mainly in response to the need to protect crops from pests that arrive by air. If the definition of biological control includes the plant induced or genetically modified to defend itself, as it should, then biological control has been the most significant approach to plant health management during the twentieth century and promises through modern biotechnology to be even more significant in the twenty-first century. Rather than "reducing losses," the advances are discussed here within the simple framework of achieving the attainable yield by increasing the actual and/or affordable and hence the average yield. Each of these four benchmark yields, as well as the absolute yield for crops, and their significance to the goals and achievements of plant health management are defined. Plant health management is a moving target, which I discuss metaphorically like an American football game, where one team is science and technology and the other is nature, where the S & T team is only beginning to know nature's rules while playing itself with the three sets of rules written to, respectively, satisfy the laws of economics, protect the environment, and gain social acceptance.

Notes: Abstract Lipopolysaccharides (LPSs) are ubiquitous, indispensable components of the cell surface of Gram-negative bacteria that apparently have diverse roles in bacterial pathogenesis of plants. As an outer membrane component, LPS may contribute to the exclusion of plant-derived antimicrobial compounds promoting the ability of a bacterial plant pathogen to infect plants. In contrast, LPS can be recognized by plants to directly trigger some plant defense-related responses. LPS can also alter the response of plants to subsequent bacterial inoculation; these delayed effects include alterations in the expression patterns of genes coding for some pathogenesis-related (PR) proteins, promotion of the synthesis of antimicrobial hydroxycinnamoyl-tyramine conjugates, and prevention of the hypersensitive reaction caused by avirulent bacteria. Prevention of the response may allow expression of resistance in the absence of catastrophic tissue damage. Recognition of LPS (and other nonspecific determinants) may initiate responses in plants that restrict the growth of nonpathogenic bacteria, whereas plant pathogens may possess hrp gene-dependent mechanisms to suppress such responses.

Notes: Abstract The family Closteroviridae comprises more than 30 plant viruses with flexuous, filamentous virions and includes representatives with either mono- or bipartite positive-strand ssRNA genomes. Closteroviruses are transmitted semipersistently by insects from three families of Homoptera, in infected plants are associated with phloem tissue, and demonstrate an astonishing genetic diversity that suggests extensive, on-going evolution. Phylogenetic analyses of their replicative genes as well as the conserved HSP70 demonstrate that closteroviruses co-evolved with their insect vectors, resulting in three major lineages, i.e. aphid-, mealybug-, and whitefly-transmitted viruses. Closteroviruses apparently represent an ancient and diverse virus family that may pose threats to agriculture and needs serious attention.

Notes: Abstract The population structure and ecological roles of the indigenous pathogen Phellinus weirii, cause of laminated root rot in conifer forests of western North America, are examined. This pathogen kills trees in slowly expanding mortality centers, creating gaps in the forest canopy. It is widespread, locally abundant, and very long-lived. It is among the most important disturbance agents in the long intervals between stand-replacing events such as wildfire or harvest in these ecosystems and shapes the structure and composition of both wild and managed forests. Trees are infected and killed regardless of individual vigor. Management of public lands is changing dramatically, with renewed emphasis on natural forest structures and processes but pathogens, especially root rot fungi, remain a significant challenge to "ecosystem management."

Notes: Abstract Wheat (Triticum aestivum L) is grown throughout the grasslands from southern Mexico into the prairie provinces of Canada, a distance of nearly 4200 km. The total area seeded to wheat varies considerably each year; however, from 28 to 32 million ha are planted in the Great Plains of the United States alone. Generally in the central Great Plains, an area from central Texas through central Nebraska, 15 million ha are seeded to winter wheat each year. A wide range of environmental conditions exist throughout this area that may affect the development and final severity of wheat leaf rust (caused by Puccinia triticina L), stripe rust (caused by P. striiformis), and stem rust (caused by P. graminis Pers. f. sp tritici) epidemics and the subsequent reduction in wheat yields. Variation in severity of rust epidemics in this area depends on differences in crop maturity at the time of infection by primary inoculum, host resistance used, and environmental conditions. The interrelationships among time, host, pathogen and environment are complex, and studying the interactions is very difficult. Historically, cultivars with new or different leaf rust resistance genes become ineffective after several years of large-scale production within the Great Plains, and then cultivars carrying new or different resistance genes must be developed and released into production. This is the typical "boom and bust" cycle of the cereal rust resistance genes in the central Great Plains.

Notes: Abstract Host plant resistance has been used extensively for disease control in many crop species; however, the resistance conferred by many sources is not durable as a result of rapid changes in the pathogen. Although many resistance genes have been identified in plant germplasm, there is no easy way to predict the quality or durability of these resistance genes. In this review, we revisit the hypothesis that resistance genes imposing a high penalty to the pathogen for adaptation will likely be durable. By elucidating the molecular changes involved in pathogen adaptation and the associated fitness cost, a proactive approach may be developed to predict the durability of resistance genes available for deployment.

Notes: Abstract The Burkholderia cepacia complex (Bcc) consists of several species of closely related and extremely versatile gram-negative bacteria found naturally in soil, water, and the rhizosphere of plants. Strains of Bcc have been used in biological control of plant diseases and bioremediation, while some strains are plant pathogens or opportunistic pathogens of humans with cystic fibrosis. The ecological versatility of these bacteria is likely due to their unusually large genomes, which are often comprised of several (typically two or three) large replicons, as well as their ability to use a large array of compounds as sole carbon sources. The original species B. cepacia has been split into eight genetic species (genomovars), including five named species, but taxonomic distinctions have not enabled biological control strains to be clearly distinguished from human pathogenic strains. This has led to a reassessment of the risk of several strains registered by the U.S. Environmental Protection Agency for biological control. We review the biology of Bcc bacteria, especially how our growing knowledge of Bcc ecology and pathogenicity might be used in risk assessment. The capability of this bacterial complex to cause disease in plants and humans, as well as to control plant diseases, affords a rare opportunity to explore traits that may function in all three environments.

Notes: Abstract Fungal pathogens cause many of the most serious crop diseases. One of the principal reasons for the success of this group is their ability to locate and perceive appropriate host surfaces and then to elaborate specialized infection structures. Here we review the processes implicated in surface attachment, germ tube elongation, and development of appressoria. The involvement of surface-acting proteins such as fungal hydrophobins and integrins in these processes is evaluated, along with a description of studies that have revealed the existence of conserved signaling pathways that regulate appressorium formation. Finally, we anticipate the prospect of genome-level analysis of fungal pathogens and the key research questions that will need to be addressed.

Notes: Abstract The fungi are the most economically important plant pathogens and continue to be the focus of extensive research with a wide variety of methodologies. Enhancements in microscopy techniques have increased our ability to visualize the intimate interaction of fungi and their host plants. Improving methods allow pharmacological inhibition and genetic dissection of the determinants of fungal pathogenicity in a gene-by-gene approach. Identification and analysis of genes differentially transcribed in ways pertinent to pathogenicity continues to be a frequent research approach. Genome-wide analysis is gaining favor in biological research and fungal plant pathogens are no exception. Several industrial research groups are exploring fungal plant pathogenesis based on genomic sequence data and genome-wide mutagenesis. In March 2001 the first publicly available complete genome of a filamentous fungus (Neurospora crassa) was released. N. crassa is of course a saprophyte and there is no complete sequence available for a plant pathogenic fungus in public databases. However, freely accessible entire genome sequences for both plant pathogenic fungi and their hosts are on the horizon. Sequence availability promises to revolutionize the rate at which data relevant to disease processes will be accrued. In this review we describe approaches currently applied to the study of plant pathogenic fungi and explore developments of potential future benefit with existing technologies not yet applied to this group of important organisms.

Notes: Abstract This review deals with a comparative analysis of seven genome sequences from plant-associated bacteria. These are the genomes of Agrobacterium tumefaciens, Mesorhizobium loti, Sinorhizobium meliloti, Xanthomonas campestris pv campestris, Xanthomonas axonopodis pv citri, Xylella fastidiosa, and Ralstonia solanacearum. Genome structure and the metabolism pathways available highlight the compromise between the genome size and lifestyle. Despite the recognized importance of the type III secretion system in controlling host compatibility, its presence is not universal in all necrogenic pathogens. Hemolysins, hemagglutinins, and some adhesins, previously reported only for mammalian pathogens, are present in most organisms discussed. Different numbers and combinations of cell wall degrading enzymes and genes to overcome the oxidative burst generally induced by the plant host are characterized in these genomes. A total of 19 genes not involved in housekeeping functions were found common to all these bacteria.

Notes: Abstract The structural proteins of plant viruses have evolved to self-associate into complex macromolecules that are centrally involved in virus biology. In this review, the structural and biophysical properties of the Tobacco mosaic virus (TMV) coat protein (CP) are addressed in relation to its role in host resistance and disease development. TMV CP affects the display of several specific virus and host responses, including cross-protection, systemic virus movement, hypersensitive disease resistance, and symptom development. Studies indicate that the three-dimensional structure of CP is critical to the control of these responses, either directly through specific structural motifs or indirectly via alterations in CP assembly. Thus, both the structure and assembly of the TMV CP function as determinants in the induction of disease and resistance responses.

Notes: Abstract Agricultural soils suppressive to soilborne plant pathogens occur worldwide, and for several of these soils the biological basis of suppressiveness has been described. Two classical types of suppressiveness are known. General suppression owes its activity to the total microbial biomass in soil and is not transferable between soils. Specific suppression owes its activity to the effects of individual or select groups of microorganisms and is transferable. The microbial basis of specific suppression to four diseases, Fusarium wilts, potato scab, apple replant disease, and take-all, is discussed. One of the best-described examples occurs in take-all decline soils. In Washington State, take-all decline results from the buildup of fluorescent Pseudomonas spp. that produce the antifungal metabolite 2,4-diacetylphloroglucinol. Producers of this metabolite may have a broader role in disease-suppressive soils worldwide. By coupling molecular technologies with traditional approaches used in plant pathology and microbiology, it is possible to dissect the microbial composition and complex interactions in suppressive soils.

Notes: Abstract Losses from postharvest fruit diseases range from 1 to 20 percent in the United States, depending on the commodity. The application of fungicides to fruits after harvest to reduce decay has been increasingly curtailed by the development of pathogen resistance to many key fungicides, the lack of replacement fungicides, negative public perception regarding the safety of pesticides and consequent restrictions on fungicide use. Biological control of postharvest diseases (BCPD) has emerged as an effective alternative. Because wound-invading necrotrophic pathogens are vulnerable to biocontrol, antagonists can be applied directly to the targeted area (fruit wounds), and a single application using existing delivery systems (drenches, line sprayers, on-line dips) can significantly reduce fruit decays. The pioneering biocontrol products BioSave and Aspire were registered by EPA in 1995 for control of postharvest rots of pome and citrus fruit, respectively, and are commercially available. The limitations of these biocontrol products can be addressed by enhancing biocontrol through manipulation of the environment, using mixtures of beneficial organisms, physiological and genetic enhancement of the biocontrol mechanisms, manipulation of formulations, and integration of biocontrol with other alternative methods that alone do not provide adequate protection but in combination with biocontrol provide additive or synergistic effects.

Notes: Carl von Tubeuf, a founder of plant pathology in Europe, pioneered biological control of a major plant disease and introduced the term "biological control" to plant pathology. His book on plant diseases was one of the first to be published in English. He was proficient in many areas, and his interests included plant diseases, mycology, forest insects, white pine blister rust, the mistletoes, plant protection laws, and nature conservation.

Notes: Gibberella species are destructive plant pathogens, although many are more familiar under their Fusarium anamorph names. The recent synthesis of phylogenetic, biological, and morphological species approaches has revitalized taxonomy of a genus that was first described almost 200 years ago. Twelve sexual species of Gibberella of agricultural importance were selected for this review to represent phylogenetic, biological, and chemical diversity of the genus. Even closely related Gibberella species can differ in reproductive mode, geographic and host distribution, plant pathogenesis, and production of toxins and other biologically active metabolites. Gibberella species have proven amenable to meiotic and molecular genetic analysis; A complete genome sequence of G. zeae should soon be available. Combining gene disruption strategies with new genomics technologies for expression profiling should help plant pathologists to understand the pathological and evolutionary significance of biological and chemical diversity in Gibberella and to identify novel strategies for disease control.

Notes: The U.S. National Research Council (NRC) concluded in 2002 that U.S. agriculture is vulnerable to attack and that the country has inadequate plans for dealing with agricultural bioterrorism. This article addresses the vulnerability of U.S. crops to attack from biological weapons by reviewing the costs and impact of plant diseases on crops, pointing out the difficulty in preventing deliberate introduction of pathogens and discovering new disease outbreaks quickly, and discussing why a plant pathogen might be chosen as a biological weapon. To put the threat into context, a brief historical review of anti-crop biological weapons programs is given. The argument is made that the country can become much better prepared to counter bioterrorism by developing a list of likely anti-crop threat agents, or categories of agents, that is based on a formal risk analysis; making structural changes to the plant protection system, such as expanding diagnostic laboratories, networking the laboratories in a national system, and educating first responders; and by increasing our understanding of the molecular biology and epidemiology of threat agents, which could lead to improved disease control, faster and more sensitive diagnostic methods, and predictions of disease invasion, persistence, and spread following pathogen introduction.

Notes: Parasitic nematodes that infect humans, animals, and plants cause serious diseases that are deleterious to human health and agricultural productivity. Chemical and biological control methods have reduced the impact of these parasites. However, surviving environmental stages lead to persistent reinfection of host species. In addition, development of resistance to nematicides and anthelmintics by these parasites and reduced availability of some nematicides, for environmental protection, pose significant obstacles for current and future prospects of effective parasite control. Due to marked differences in host species, research on animal and plant parasitic nematodes often proceeds independently. Despite the differences between animals and plants, basic cellular properties are shared among these host organisms. Some common properties may be important for mechanisms [homologous or convergent (homoplastic)] by which nematodes successfully infect these diverse hosts or by which animal and plant hosts resist infections by these pathogens. Here we compare host/parasite interactions between plant parasitic nematodes (PPN) and animal parasitic nematodes, with an emphasis on mammalian hosts (MPN). Similarities and differences are considered in the context of progress on molecular dissection of these interactions. A comprehensive coverage is not possible in the space allotted. Instead, an illustrative approach is used to establish examples that, it is hoped, exemplify the value of the comparative approach.

Notes: Mycorrhizae regulate elemental and energy flows in terrestrial ecosystems. We understand much of how mycorrhizae work, but integrating all possible mechanisms into a whole has proven elusive. Multiple evolutionary events and the long evolutionary history mean that different plants and fungi bring independent characteristics to the symbiosis. This variety results in extensive physiological variation. How do we integrate functional responses with diversity to understand the role of mycorrhizae in ecosystems? We review ecophysiological mechanisms of mycorrhizae and organize these into functional groups. Species-area relationships are not curvilinear, but resemble the "broken stick" model. We coupled functional groups with a metacommunity analysis to show how complex behavior can be generated using a simple matrix model of resource exchange. This approach provides insights into how we might integrate diversity and function across landscapes.

Notes: The current standard treatment for management of soilborne pests in some high-value crop production systems is preplant fumigation with mixtures of methyl bromide and chloropicrin. With the impending phase-out of methyl bromide, the agricultural industries that rely on soil fumigation face the need for development of alternative pest management strategies. To maintain farm productivity, immediate term research has focused on evaluation of alternative fumigants, modification of current crop production practices to accommodate their use, and improvement of application technologies to reduce the environmental effects of fumigant applications. Longer-term research goals have focused on developing a more integrated approach for pest management that incorporates the use of cultural practices to reduce pathogen pressure, host resistance to disease, and biological approaches for stimulating plant growth and control of root diseases.

Notes: Members of the Luteoviridae are transmitted by aphids in a circulative, nonpropagative manner that requires the virus to be acquired through gut tissue into the aphid hemocoel and then exit through salivary tissues. This process is aphid species-specific and involves specific recognition of the virus by unidentified components on the membranes of gut and salivary tissues. Transport through the tissues is an endocytosis/exocytosis process. Both structural proteins of the virus are involved in the transmission process, with multiple protein domains regulating the movement and survival of the virus in the aphid and plant. Here we review what is known about the genetic, cellular, and molecular mechanisms regulating these complex and specific virus-aphid interactions.

Notes: Beet necrotic yellow vein virus (BNYVV) and Beet soilborne mosaic virus (BSBMV) are members of the genus Benyvirus, and Burdock mottle virus (BdMV) is a tentative member. BNYVV and BSBMV are vectored by the plasmodiophorid Polymyxa betae, which has a worldwide distribution. Polymyxa betae is morphologically indistinguishable from P. graminis, but recent molecular studies support separation of the two species. The geographic distribution of BNYVV is also worldwide, but BSBMV has been identified only in the United States. In Europe and Japan, several genotypic strains of BNYVV have been identified, and those with a fifth RNA appear to be more aggressive. No thorough survey of genotypic variability of BNYVV or BSBMV has been conducted in the United States. However, both viruses are widespread and frequently found in the same field, infecting the same beet plant. The implications of this close proximity, with regard to disease incidence and severity, and for recombination, are uncertain. Recent technological advances that permit improved detection and quantification of these viruses and their vector offer tremendous research opportunities.

Notes: Parasitic biotrophs such as mildews and rusts evolved specific mechanisms that keep host cells alive during infection. These fungi appear to absorb nutrients mainly by proton-symport-driven transporter proteins that reside in specialized feeding structures. Accumulating evidence suggests that biotrophic fungi both suppress induction of plant defense responses in physical proximity to infection sites and induce specific host genes for the establishment of biotrophy. The peculiarities of biotrophic pathogenesis likely reflect diverse types of plant disease-resistance responses. The cloning of race-specific resistance genes to powdery mildew infection and of genes required for their function provides first insights into molecular mechanisms enabling the host to recognize mildew effector components and suggests candidate mechanisms of resistance signaling. Resistance to powdery mildew fungi that result from mutations in host genes promises to shed light on mechanisms that are required for the establishment of disease susceptibility.

Notes: This article presents the experiences of a woman in academic plant pathology from the 1950s to today. Topics include the social climate for women in science, personal and professional developments and research discoveries, public policy issues in agriculture and biotechnology affecting plant pathology, and projections for the future of plant pathology.

Notes: Abstract Plant pathology came of age at the turn of this century and we can be proud of the many significant contributions it has made to fundamental research as well as to service to growers. The twenty-first century will present our profession with dramatic challenges to meet the demands for increased food, fiber, and fuel production from a declining agricultural base. This can be accomplished only if plant pathology retains its integrity as a profession and remains abreast of advancements in the fields of biotechnology and communications.

Notes: Abstract Cornelius Lott Shear was one of the most influential plant pathologists of the early twentieth century. He was first and foremost an excellent mycologist who did pioneering research on pathogenic fungi and, as a senior pathologist with the USDA's Bureau of Plant Industry, studied important crop diseases and offered useful control measures. Shear's successful research enhanced his reputation among his fellow pathologists and allowed him to embark on what was perhaps his most significant contribution to plant pathology, his pivotal role in the creation of the American Phytopathological Society in 1908. Shear felt that an independent society dedicated to the unique needs of plant pathologists would facilitate communication and cooperation among practitioners. Between his scientific research and his role in the creation of APS, Shear stands out for the enormous impact he had on his science.

Notes: Abstract The twentieth century has been productive for the science of plant pathology and the field of host-parasite interactions-both in understanding how pathogens and plant defense work and in developing more effective means of disease control. Early in the twentieth century, plant pathology adopted a philosophy that encouraged basic scientific investigation of pathogens and disease defense. That philosophy led to the strategy of developing disease-resistant plants as a prima facie disease-control measure-and in the process saved billions of dollars and avoided the use of tons of pesticides. Plant pathology rapidly adopted molecular cloning and its spin-off technologies, and these have fueled major advances in our basic understanding of plant diseases. This knowledge and the development of efficient technologies for producing transgenic plants convey optimism that plant diseases will be more efficiently controlled in the twenty-first century.

Notes: Abstract Interest in the rust fungi derives from their success as plant pathogens. For example, the epidemic on coffee had serious economic and social impacts on diverse cultures. During the century, research on the rust germling shifted from a study of germling development, including a search for the signals that induce differentiation, to an examination of the genes expressed during host colonization. Research on host resistance was most influenced by Stakman, who studied the genetics and epidemiology of rust disease. His innovations enabled Flor to propose the gene-for-gene hypothesis, a concept that stimulated development of resistant crops, and led to research that gradually shifted during the century to an examination of the molecular basis of rust genetics.

Notes: The genome structures of a large number of viruses transmitted by olpidium and plasmodiophorid vectors have been determined. The viruses are highly diverse, belonging to 12 genera in at least 4 families. Plasmodiophorids are now classified as protists rather than true fungi. This finding, along with the recognition of the great variety of viruses transmitted by olpidium and plasmodiophorid vectors, will likely lead to an elaboration of the details of in vitro and in vivo transmission mechanisms. Recent progress in elucidating the interaction between Cucumber necrosis virus (CNV) and its zoospore vector suggests that specific sites on the capsid as well as on the zoospore are involved in transmission. Moreover, some features of CNV/zoospore attachment are similar to poliovirus/host cell interactions, suggesting evolutionary conservation of functional features of plant and animal virus capsids.

Notes: Many phytopathogenic bacteria inject virulence effector proteins into plant cells via a Hrp type III secretion system (TTSS). Without the TTSS, these pathogens cannot defeat basal defenses, grow in plants, produce disease lesions in hosts, or elicit the hypersensitive response (HR) in nonhosts. Pathogen genome projects employing bioinformatic methods to identify TTSS Hrp regulon promoters and TTSS pathway targeting signals suggest that phytopathogenic Pseudomonas, Xanthomonas, and Ralstonia spp. harbor large arsenals of effectors. The Hrp TTSS employs customized cytoplasmic chaperones, conserved export components in the bacterial envelope (also used by the TTSS of animal pathogens), and a more specialized set of TTSS-secreted proteins to deliver effectors across the plant cell wall and plasma membrane. Many effectors can act as molecular double agents that betray the pathogen to plant defenses in some interactions and suppress host defenses in others. Investigations of the functions of effectors within plant cells have demonstrated the plasma membrane and nucleus as subcellular sites for several effectors, revealed some effectors to possess cysteine protease or protein tyrosine phosphatase activity, and provided new clues to the coevolution of bacterium-plant interactions.

Notes: Although many subviral RNAs reduce or intensify disease symptoms caused by the helper virus, only recently have clues concerning the mechanism of disease modulation been revealed. New models for DI RNA-mediated reduction in helper virus levels and symptom attenuation include DI RNA enhancement of posttranscriptional gene silencing (PTGS), which is an antiviral defense mechanism in plants. Symptom enhancement by the satRNA of Cucumber mosaic virus is caused by minus-strand induction of the programmed cell death pathway. In contrast, symptom enhancement by satC of Turnip crinkle virus is due to satC interference with virion formation, leading to increased levels of free coat protein, which is the viral suppressor of PTGS. Mutualism between satRNA and helper virus can be seen for the satRNA of Groundnut rosette virus, which contributes to the virus by allowing virion assembly. These novel findings are leading to re-evaluation of the relationships between subviral RNAs, helper viruses, and hosts.

Notes: Abstract Much attention has focused on the effects of leptin as a central satiety agent. There is now a significant amount of evidence that leptin is active in the periphery. This review focuses on the ability of leptin to modify insulin sensitivity, tissue metabolism, stress responses, and reproductive function. Leptin's effect on several of these systems is mediated via the hypothalamic-pituitary axis. Therefore, although in vitro studies provide evidence for direct effects on specific tissues and metabolic pathways, it is essential to consider the interactions between leptin and other regulatory factors in vivo. Little is known about the regulation of peripheral receptor expression or the production of binding proteins. Both of these factors determine the bioactivity of circulating leptin and have the potential to induce a peripheral resistance to leptin, similar to the central "leptin resistance" observed in obese subjects. Future research will clarify which of the endocrine and metabolic actions of peripheral leptin are of physiological relevance and which should be considered a pharmacological manipulation.

Notes: Abstract Fasting or malnutrition (FM) has dramatic effects on small intestinal mucosal structure and transport function. Intestinal secretion of ions and fluid is increased by FM both under basal conditions and in response to secretory agonists. Intestinal permeability to ions and macromolecules may also be elevated by FM, which increases the potential for fluid and electrolyte losses and for anaphylactic responses to luminal antigens. Mucosal atrophy induced by FM reduces total intestinal absorption of nutrients, but nutrient absorption normalized to mucosal mass may actually be enhanced by a variety of mechanisms, including increased transporter gene expression, electrochemical gradients, and ratio of mature to immature cells. These observations underscore the value of enteral feeding during health and disease.

Notes: Abstract The transport and cellular metabolism of Cu depends on a series of membrane proteins and smaller soluble peptides that comprise a functionally integrated system for maintaining cellular Cu homeostasis. Inward transport across the plasma membrane appears to be a function of integral membrane proteins that form the channels that select Cu ions for passage. Two membrane-bound Cu-transporting ATPase enzymes, ATP7A and ATP7B, the products of the Menkes and Wilson disease genes, respectively, catalyze an ATP-dependent transfer of Cu to intracellular compartments or expel Cu from the cell. ATP7A and ATP7B work in concert with a series of smaller peptides, the copper chaperones, that exchange Cu at the ATPase sites or incorporate the Cu directly into the structure of Cu-dependent enzymes such as cytochrome c oxidase and Cu, Zn superoxide dismutase. These mechanisms come into play in response to a high influx of Cu or during the course of normal Cu metabolism.

Notes: Abstract Hormone-sensitive lipase, the rate-limiting enzyme of intracellular TG hydrolysis, is a major determinant of fatty acid mobilization in adipose tissue as well as other tissues. It plays a pivotal role in lipid metabolism, overall energy homeostasis, and, presumably, cellular events involving fatty acid signaling. Detailed knowledge about its structure and regulation may provide information regarding the pathogenesis of such human diseases as obesity and diabetes and may generate concepts for new treatments of these diseases. The current review summarizes the recent advances with regard to hormone-sensitive lipase structure and molecular mechanisms involved in regulating its activity and lipolysis in general. A summary of the current knowledge regarding regulation of expression, potential involvement in lipid disorders, and role in tissues other than adipose tissue is also provided.

Notes: Abstract The major transcriptional factors involved in the adipogenic process include proteins belonging to the CCAAT/enhancer binding protein family, peroxisome proliferator-activated receptor gamma, and adipocyte determination and differentiation dependent factor 1, also known as sterol regulatory element-binding protein 1. This process has been characterized with the aid of cell lines that represent various stages in the path of adipocyte commitment, ranging from pluripotent mesodermal fibroblasts to preadipocytes. Molecular analyses have led to a cascade model for adipogenesis based on timed expression of CCAAT/enhancer-binding proteins and peroxisome proliferator-activated receptor gamma. Gene targeting and transgenic-mouse technologies, which allow the manipulation of endogenous genes for these transcription factors, have also contributed to the understanding of adipogenesis. This review aims to integrate this information to gain an understanding of the transcriptional regulation of fat cell formation.

Notes: Abstract Epidemiologic studies from numerous disparate populations reveal that individuals with the habit of daily moderate wine consumption enjoy significant reductions in all-cause and particularly cardiovascular mortality when compared with individuals who abstain or who drink alcohol to excess. Researchers are working to explain this observation in molecular and nutritional terms. Moderate ethanol intake from any type of beverage improves lipoprotein metabolism and lowers cardiovascular mortality risk. The question now is whether wine, particularly red wine with its abundant content of phenolic acids and polyphenols, confers additional health benefits. Discovering the nutritional properties of wine is a challenging task, which requires that the biological actions and bioavailability of the 〉200 individual phenolic compounds be documented and interpreted within the societal factors that stratify wine consumption and the myriad effects of alcohol alone. Further challenge arises because the health benefits of wine address the prevention of slowly developing diseases for which validated biomarkers are rare. Thus, although the benefits of the polyphenols from fruits and vegetables are increasingly accepted, consensus on wine is developing more slowly. Scientific research has demonstrated that the molecules present in grapes and in wine alter cellular metabolism and signaling, which is consistent mechanistically with reducing arterial disease. Future research must address specific mechanisms both of alcohol and of polyphenolic action and develop biomarkers of their role in disease prevention in individuals.

Notes: Abstract A range of compounds in or derived from the diet modulates apoptosis in cell cultures in vitro. These observations have important implications concerning the mechanisms whereby dietary components affect health. Proapoptotic compounds could protect against cancer by enhancing elimination of initiated, precancerous cells, and antiapoptotic compounds could promote tumor formation by inhibiting apoptosis in genetically damaged cells. Proapoptotic compounds could also contribute to age-related degenerative diseases by activating cell death in postmitotic cells or shifting the normal balance of mitosis and apoptosis in tissues with regenerative capacity. Many age-related diseases, for example macular degeneration and Parkinson's disease, appear to have oxidative stress as an underlying component that interacts with genetic, dietary, and environmental factors to determine relative risk in an individual. Oxidative stress activates apoptosis, and antioxidants protect against apoptosis in vitro; thus, a central role of dietary antioxidants may be to protect against apoptosis. However, little in vivo data are available to directly link diet with altered apoptosis as an underlying determinant of disease. Moreover, the possible antagonistic effects of different dietary components and the uncertainty about whether proapoptotic compounds that may protect against cancer could contribute to degenerative diseases and vice versa indicate that there is a great need for better in vivo assessment of apoptosis and that caution should be exercised when extrapolating in vitro data on apoptosis to in vivo dietary recommendations.

Notes: Abstract Polarized epithelia have several functional and morphological similarities, including a high capacity for uptake of various substances present in the fluids facing the apical epithelial surfaces. Studies during the past decade have shown that receptor-mediated endocytosis, rather than nonspecific pinocytosis, accounts for the apical epithelial uptake of many carrier-bound nutrients and hormones. The two interacting receptors of distinct evolutionary origin, megalin and cubilin, are main receptors in this process. Both receptors are apically expressed in polarized epithelia, in which they function as biological affinity matrices for overlapping repertoires of ligands. The ability to bind multiple ligands is accounted for by a high number of replicated low-density lipoprotein receptor type-A repeats in megalin and CUB (complement C1r/C1s, Uegf, and bone morphogenic protein-1) domains in cubilin. Here we summarize and discuss the structural, genetic, and functional aspects of megalin and cubilin, with emphasis on their function as receptors for uptake of protein-associated vitamins, lipids, and hormones.

Notes: Abstract Obesity is now recognized as a serious chronic disease, but there is pessimism about how successful treatment can be. A general perception is that almost no one succeeds in long-term maintenance of weight loss. To define long-term weight loss success, we need an accepted definition. We propose defining successful long-term weight loss maintenance as intentionally losing at least 10% of initial body weight and keeping it off for at least 1 year. According to this definition, the picture is much more optimistic, with perhaps greater than 20% of overweight/obese persons able to achieve success. We found that in the National Weight Control Registry, successful long-term weight loss maintainers (average weight loss of 30 kg for an average of 5.5 years) share common behavioral strategies, including eating a diet low in fat, frequent self-monitoring of body weight and food intake, and high levels of regular physical activity. Weight loss maintenance may get easier over time. Once these successful maintainers have maintained a weight loss for 2-5 years, the chances of longer-term success greatly increase.

Notes: Abstract Accurate assessment of dietary intake among preschool-aged children is important for clinical care and research, for nutrition monitoring and evaluating nutrition interventions, and for epidemiologic research. We identified 25 studies published between January 1976 and August 2000 that evaluated the validity of food recalls (n = 12), food frequency questionnaires (n = 9), food records (n = 2), or other methods (n = 2). We identified four studies that evaluated the reproducibility of food frequency questionnaires. Validity studies varied in validation standard and study design, making comparisons between studies difficult. In general, food frequency questionnaires overestimated total energy intake and were better at ranking, than quantifying, nutrient intake. Compared with the validation standard, food recalls both overestimated and underestimated energy intake. When choosing a method to estimate diet, both purpose of the assessment and practicality of the method must be considered, in addition to the validity and reproducibility reported in the scientific literature.

Notes: Abstract Poor people in developing countries endure the burden of disease caused by four common species of soil-transmitted nematode that inhabit the gastrointestinal tract. Disease accompanying these infections is manifested mainly as nutritional disturbance, with the differing infections having their deleterious effects at different phases during the human life cycle. Reduced food intake, impaired digestion, malabsorption, and poor growth rate are frequently observed in children suffering from ascariasis and trichuriasis. Poor iron status and iron deficiency anemia are the hallmarks of hookworm disease. The course and outcome of pregnancy, growth, and development during childhood and the extent of worker productivity are diminished during hookworm disease. Less is known about the impact of these infections in children under 2 years of age. The severity of disease caused by soil-transmitted nematodes has consistently been found to depend on the number of worms present per person. Cost-effective measures based on highly efficacious anthelminthic drugs are now available to reduce and control disease caused by these infections.

Notes: Abstract The health benefits of pre- and probiotics have been the subject of increased research interests. These food supplements have been demonstrated to alter the pre-existing intestinal flora so as to provide an advantage to the host. This review focuses on the scientific evidence both for and against their role in promoting health and treating disease. Specific attention is turned to their effects on immunomodulation, lipid metabolism, cancer prevention, diarrhea, Helicobacter pylori, necrotizing enterocolitis, allergy, and inflammatory bowel disease.

Notes: Abstract DNA methylation at cytosines in CpG dinucleotides can lead to changes in gene expression and function without altering the primary sequence of the DNA. Methylation can be affected by dietary levels of methyl-donor components, such as folic acid. This may be an important mechanism for environmentally induced changes in gene expression. Recent literature supports a role for DNA-methylation changes in a number of adult-onset disorders and during development. These changes may be significant for better understanding certain birth defects (e.g., neural tube defects) and the long-term consequences of early environmental influences on gene expression (metabolic programming). Optimal "methylation diets" should be investigated as part of the prevention and treatment of all these conditions, as well as in disorders such as Rett syndrome, whose primary defects may lie in DNA methylation-dependent gene regulation.

Notes: Abstract The anorexia of aging is a syndrome characterized by unexplained losses in food intake and body weight that occur near the end of life. Proposed etiologies cover a wide range of biological and psychological conditions. The observation of this phenomenon in older laboratory animals suggests that physiological changes play a significant causal role. Research on the neurochemical control of energy balance has received much attention in recent years, and age-related alterations in the neuropeptidergic effectors of food intake have been implicated in the anorexia of aging. This review provides an update on putative mechanisms underlying this dysregulation of feeding during advanced age.

Notes: Abstract The possible role of carotenoids and their metabolites in disease prevention is far from fully understood, because the bioavailabilities of carotenoids are complicated by multiple factors that affect their absorption, breakdown, transport, and storage. Rapid progress in developing sophisticated methodologies, including use of stable-isotope dilution methods, now allows for an accurate determination of the true vitamin A activity of provitamin A carotenoids. The recent identification of specific enzymes, which catalyze the breakdown of beta-carotene as well as nonprovitamin A carotenoids, is providing a better understanding of the functions of carotenoids at the molecular level. The pathways and possible mechanisms of carotenoid breakdown and factors affecting the bioavailability of carotenoids, such as carotenoid type, food matrix, interaction with other carotenoids and other food components, nutritional status, aging, and infection, are discussed in this review.

Notes: Abstract A full review of the strengths and limitations of the various methods used to define amino acid requirements is provided. The focus is on the recent development of carbon oxidation techniques such as indicator amino acid oxidation and 24-h amino acid balance to determine dietary indispensable (essential) amino acid needs in adults. All approaches depend on the change in a metabolic parameter in response to graded intake of the test amino acid. In humans, the within-subject variance is less than the between-subject variance, which has led to an appreciation of the need to study each subject across a range of intakes, above and below the mean requirement level. The data can then be analyzed using two-phase linear regression crossover and a precise population mean requirement can be determined. Several approaches have been used to define the variance of the mean requirement. Finally, a minimally invasive indicator amino acid oxidation model has been developed which allows the determination of dietary essential amino acid requirements in children and other vulnerable populations.

Notes: Abstract Atwater and his colleagues began studying food consumption in the closing years of the nineteenth century and from the very start devoted much effort to collecting data from poor and minority households. This paper reviews some of the fruits of these labors, particularly from the standpoint of what they contribute toward a better historical understanding of American food habits and nutrition. It surveys dietary data from African American, Appalachian white, Mexican American, native-born poor, and immigrant households. These data shed light on several areas of historical concern, including rural versus urban nutrition, seasonal hunger, class disparities, and food-habit change. I suggest the economically and culturally diverse sample of dietary patterns that comes to us as a legacy of the Atwater era sets the stage for a history of American food habits considerably more sophisticated than has been realized to date.

Notes: Abstract Intestinal epithelial cell turnover (proliferation, migration, differentiation, and apoptosis) and gut barrier functions are dynamic processes that are markedly affected by nutritional status, the route of feeding, and the adequacy of specific nutrients in the diet. Emerging studies are defining potential therapeutic roles for specific nutrients and diet-derived compounds (including arginine, glutamate, glutamine, glutathione, glycine, vitamin A, zinc, and specific lipids) in gut mucosal turnover, repair, adaptation after massive bowel resection, and barrier function. The role and regulation of endogenous bowel flora in generating short-chain fatty acids from diet-derived fiber and other diet-derived compounds and the effects of these agents on gut function are increasingly being elucidated. Results of these investigations should define new nutritional methods for trophic and cytoprotective effects on the intestine in conditions such as inflammatory bowel disease, malnutrition, and short bowel syndrome.

Notes: Abstract The macular region of the primate retina is yellow in color due to the presence of the macular pigment, composed of two dietary xanthophylls, lutein and zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably formed from either lutein or zeaxanthin in the retina. By absorbing blue-light, the macular pigment protects the underlying photoreceptor cell layer from light damage, possibly initiated by the formation of reactive oxygen species during a photosensitized reaction. There is ample epidemiological evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration, an irreversible process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to be protective against the development of age-related macular degeneration, a causative relationship has yet to be experimentally demonstrated.

Notes: Abstract In the postgenomic era of biology, much attention has been given to functional genomics, or the relation between genes and higher levels of organization in the cell. The latter are typically represented as mRNA, protein, or organic metabolite complements. The theme of this review is that the operational unit of function in complex biological systems is more properly seen as the fully assembled metabolic pathway in the whole organism. Due to the connectivity, interactions, and complexity of metabolic pathways, the measurement of components is an inadequate method for predicting phenotype. Measurement of the outputs of pathways (molecular fluxes) involves different tools than static measures of components, however. Here, we review recently developed stable isotope-mass spectrometric tools for measuring fluxes through metabolic pathways in vivo, focusing on the response to dietary macronutrients (carbohydrates and fats). Methods discussed include measurement of lipid dynamics, DNA replication, hepatic assembly of lipoproteins, and long-lived protein synthesis. Measuring fluxes through multiple pathways concurrently allows regulatory themes to emerge. Use of 2H2O-labeling is emerging as a particularly powerful approach for multiple concurrent biosynthetic flux measurements. Several examples demonstrate that pathway flux results are often unexpected and not predicted by classic biochemistry or the expression of genes and proteins.

Notes: Abstract Microorganisms have successfully adapted to changes in food production, processing, and preservation techniques, resulting in a number of new and emerging foodborne pathogens and the re-emergence of organisms that have been problematic in the past. To protect public health, science must meet the challenges that result from the remarkable adaptability of foodborne pathogens. However, not all of the challenges of preventing foodborne illness reside in the realm of science. Food safety policy must evolve in reponse to new scientific understanding of hazards in the food supply and an ever-changing food processing industry. The laws, regulations, and organizations comprising the food safety system frequently lag behind current scientific knowledge of the risks posed by foodborne pathogens. Future systemic changes to enhance food safety will require better understanding of risks associated with specific pathogens occurring in the food supply and the costs and benefits of implementing mitigation strategies.

Notes: Ferritin, a major form of endogenous iron in food legumes such as soybeans, is a novel and natural alternative for iron supplementation strategies where effectiveness is limited by acceptability, cost, or undesirable side effects. A member of the nonheme iron group of dietary iron sources, ferritin is a complex with Fe3+ iron in a mineral (thousands of iron atoms inside a protein cage) protected from complexation. Ferritin illustrates the wide range of chemical and biological properties among nonheme iron sources. The wide range of nonheme iron receptors matched to the structure of the iron complexes that occurs in microorganisms may, by analogy, exist in humans. An understanding of the chemistry and biology of each type of dietary iron source (ferritin, heme, Fe2+ ion, etc.), and of the interactions dependent on food sources, genes, and gender, is required to design diets that will eradicate global iron deficiency in the twenty-first century.

Notes: Soy infant formulas are widely used, but few studies have evaluated long-term safety or examined specific forms of toxicity, such as to the endocrine or immune systems. This review focuses on newer experimental studies of the effects on estrogen activity, immune function, and thyroid economy of genistein and daidzein, two isoflavones in soy infant formula, and existing human studies of soy formula use. In order to judge the likelihood that an endpoint seen in laboratory studies might occur in soy-fed infants, we examined the doses and the resulting serum or plasma concentrations from the laboratory studies and compared them with doses and concentrations seen in soy-fed infants. We also summarized the estimates of the potency of the isoflavone compounds relative to estradiol. Given the scarcity and inconsistency of existing human data and the substantial laboratory evidence of hormonal and other activity at doses relevant to the soy-fed infant, we conclude that more clinical and epidemiological study is warranted.

Notes: Animals have developed highly adaptive and redundant mechanisms to maintain energy balance by matching caloric intake to caloric expenditure. Recent evidence has pointed to a variety of peripheral signals that inform specific central nervous system (CNS) circuits about the status of peripheral energy stores as critical to the maintenance of energy balance. A critical component of these CNS circuits is the melanocortin system. Regulation of signaling by melanocortin 3 and melanocortin 4 receptors in the CNS is controlled via neuronal cell bodies in the arcuate nucleus of the hypothalamus that synthesize melanocortin receptor agonists such as alpha-melanocyte-stimulating hormone (alpha-MSH) or antagonists such as agouti-related protein (AgRP). The activity of these two populations of neurons is reciprocally regulated by a number of peripheral and central systems that influence energy balance. Further, increased melanocortin signaling via pharmacological or genetic means in the CNS causes potent reductions in food intake and weight loss. Decreased melanocortin signaling via pharmacological or genetic means results in increased food intake and weight gain. Reviewed here is the wide range of evidence that points to the melanocortin system as a critical node in the diverse neurocircuitry that regulates food intake and body weight.

Notes: Zinc is an essential micronutrient for human growth, development, and immune function. Zinc deficiency impairs overall immune function and resistance to infection. Mild to moderate zinc deficiency can be best detected through a positive response to supplementation trials. Zinc supplementation has been shown to have a positive effect on the incidence of diarrhea (18% reduction, 95% CI: 7-28%) and pneumonia (41% reduction, 95% CI: 17-59%), and might lead to a decrease in the incidence of malaria. Zinc has also proven to decrease the duration of diarrhea by 15% (95% CI: 5-24%). Maternal zinc supplementation may lead to a decrease in infant infections. Studies assessing the role of zinc supplementation among persons with HIV, tuberculosis, and the common cold have not been conclusive. Two studies have shown zinc supplementation to decrease child mortality by more than 50%. Zinc clearly has an important role in infant and childhood infectious diseases; programs to increase the intake of zinc among deficient populations are needed.

Notes: Increased longevity and improved medical management of children with chronic illnesses has led to a focus on the short- and long-term consequences of these conditions on bone health. Bone loss is influenced by diet, malabsorption, and disease-related imbalances in bone turnover. It may be exacerbated by common medications, especially corticosteroids. Assessment of bone mass and quality, calcium absorption, kinetically derived rates of bone turnover, and biochemical markers of bone turnover have increased our knowledge of the pathophysiology of bone loss in these children as well as provided insights into possible therapeutic interventions. Increased intake of calcium and vitamin D, while useful, is unlikely to prevent or resolve bone loss in many chronically ill children. Emphasis on combination of nutritional interventions with exercise and newer bone-sparing therapies may be necessary.

Notes: Identifying bioactive compounds and establishing their health effects are active areas of scientific inquiry. There are exciting prospects that select bioactive compounds will reduce the risk of many diseases, including chronic diseases such as cardiovascular disease. Recent findings have established that cardiovascular disease is a disease of inflammation, and consequently is amenable to intervention via molecules that have anti-inflammatory effects. In addition, research demonstrating adverse effects of oxidants on atherogenesis raises the possibility that antioxidants can confer cardioprotective effects. This review provides an overview of research approaches that can be used to unravel the biology and health effects of bioactive compounds. Because of the number of bioactive compounds and the diversity of likely biological effects, numerous and diverse experimental approaches must be taken to increase our understanding of the biology of bioactive compounds. Recognizing the complexity of this biology, sophisticated experimental designs and analytical methodologies must be employed to advance the field. The discovery of novel health effects of bioactive compounds will provide the scientific basis for future efforts to use biotechnology to modify/fortify foods and food components as a means to improve public health.

Notes: Abstract Although triacylglycerol stores play the critical role in an organism's ability to withstand fuel deprivation and are strongly associated with such disorders as diabetes, obesity, and atherosclerotic heart disease, information concerning the enzymes of triacylglycerol synthesis, their regulation by hormones, nutrients, and physiological conditions, their mechanisms of action, and the roles of specific isoforms has been limited by a lack of cloned cDNAs and purified proteins. Fortunately, molecular tools for several key enzymes in the synthetic pathway are becoming available. This review summarizes recent studies of these enzymes, their regulation under varying physiological conditions, their purported roles in synthesis of triacylglycerol and related glycerolipids, the possible functions of different isoenzymes, and the evidence for specialized cellular pools of triacylglycerol and glycerolipid intermediates.

Notes: Abstract Iron homeostasis is maintained by regulating its absorption: Under conditions of deficiency, assimilation is enhanced but iron uptake is otherwise limited to prevent toxicity due to overload. Iron deficiency remains the most important micronutrient deficiency worldwide, but increasing awareness of the genetic basis for iron-loading diseases points to iron overload as a major public health issue as well. Recent identification of mutant alleles causing iron uptake disorders in mice and humans provides new insights into the mechanisms involved in iron transport and its regulation. This article summarizes these discoveries and discusses their impact on our current understanding of iron transport and its regulation.

Notes: Abstract Pregnancy and lactation are periods of high calcium requirement. This review highlights recent advances in our understanding of calcium and bone metabolism during human pregnancy and lactation and discusses the findings in relation to the calcium nutrition of the mother. The evidence indicates that pregnancy and lactation are characterized by physiological adaptive processes that are independent of maternal calcium intake and that provide the calcium necessary for fetal growth and breast-milk production without requiring an increase in maternal calcium intake. There are firm data that demonstrate that a low calcium intake during lactation does not lead to impaired lactational performance or to exaggerated bone loss. However, more research is required to define whether a low calcium intake prior to or during pregnancy can have deleterious effects on reproductive and lactational performance, and on the long-term health of the mother and child.

Notes: Abstract Four recently discovered homologues of the brown adipose tissue-specific mitochondrial uncoupling protein (UCP1) vary from 29% to 58% in their similarity to UCP1. Although these homologues share important structural features with UCP1 and like UCP1 can reduce the mitochondrial membrane potential when expressed in yeast, there is no clear evidence that they can function thermogenically in vivo. On the other hand, evidence continues to accumulate indicating that the up-regulation of Ucp1 reduces excessive adiposity.

Notes: Abstract In the past, alcoholic liver disease was attributed exclusively to dietary deficiencies, but experimental and judicious clinical studies have now established alcohol's hepatotoxicity. Despite an adequate diet, it can contribute to the entire spectrum of liver diseases, mainly by generating oxidative stress through its microsomal metabolism via cytochrome P4502E1 (CYP2E1). It also interferes with nutrient activation, resulting in changes in nutritional requirements. This is exemplified by methionine, one of the essential amino acids for humans, which needs to be activated to S-adenosylmethionine (SAMe), a process impaired by liver disease. Thus, SAMe rather than methionine is the compound that must be supplemented in the presence of significant liver disease. In baboons, SAMe attenuated mitochondrial lesions and replenished glutathione; it also significantly reduced mortality in patients with Child A or B cirrhosis. Similarly, decreased phosphatidylethanolamine methyltransferase activity is associated with alcoholic liver disease, resulting in phosphatidylcholine depletion and serious consequences for the integrity of membranes. This can be offset by polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated phosphatidylcholines comprising dilinoleoylphosphatidylcholine (DLPC), which has high bioavailability. PPC (and DLPC) opposes major toxic effects of alcohol, with down-regulation of CYP2E1 and reduction of oxidative stress, deactivation of hepatic stellate cells, and increased collagenase activity, which in baboons, results in prevention of ethanol-induced septal fibrosis and cirrhosis. Corresponding clinical trials are ongoing.

Notes: Abstract Traditional food resources of indigenous peoples are now recognized as containing a variety of environmental contaminants which reach food species through local or long-range transport avenues. In this chapter we review the published reports of contaminants contained in traditional food in northern North America and Europe as organochlorines, heavy metals, and radionuclides. Usually, multiple contaminants are contained in the same food species. Measurement of dietary exposure to these environmental contaminants is reviewed, as are major issues of risk assessment, evaluation, and management. The dilemma faced by indigenous peoples in weighing the multiple nutritional and socioeconomic benefits of traditional food use against risk of contaminants in culturally important food resources is described.

Notes: Abstract Nutritional iron deficiency (ID) is caused by an intake of dietary iron insufficient to cover physiological iron requirements. Studies on iron absorption from whole diets have examined relationships between dietary iron bioavailability/absorption, iron losses, and amounts of stored iron. New insights have been obtained into regulation of iron absorption and expected rates of changes of iron stores or hemoglobin iron deficits when bioavailability or iron content of the diet has been modified and when losses of iron occur. Negative effects of ID are probably related to age, up to about 20 years, explaining some of earlier controversies. Difficulties in establishing the prevalence of mild ID are outlined. The degree of underestimation of the prevalence of mild ID when using multiple diagnostic criteria is discussed. It is suggested that current low-energy lifestyles are a common denominator for the current high prevalence not only of ID but also of obesity, diabetes, and osteoporosis.

Notes: Abstract Long-chain fatty acids are a vital metabolic energy source and are building blocks of membrane lipids. The yeast Saccharomyces cerevisiae is a valuable model system for elucidation of gene-function relationships in such eukaryotic processes as fatty acid metabolism. Yeast degrades fatty acids only in the peroxisome, and recently, genes encoding core and auxiliary enzymes of peroxisomal beta-oxidation have been identified. Mechanisms involved in fatty acid induction of gene expression have been described, and novel fatty acid-responsive genes have been discovered via yeast genome analysis. In addition, a number of genes essential for synthesis of the variety of fatty acids in yeast have been cloned. Advances in understanding such processes in S. cerevisiae will provide helpful insights to functional genomics approaches in more complex organisms.