bluuebunny/crossref_metadata_2025 huggingface dataset:
Cow's Milk and Linear Growth in Industrialized and Developing Countries
Authors: Hoppe Camilla , Mølgaard Christian , Michaelsen Kim F.
Published: April 2006

▪ Abstract  The strongest evidence that cow's milk stimulates linear growth comes from observational and intervention studies in developing countries that show considerable effects. Additionally, many observational studies from well-nourished populations also show an association between milk intake and growth. These results suggest that milk has a growth-stimulating effect even in situations where the nutrient intake is adequate. This effect is supported by studies that show milk intake stimulates circulating insulin-like growth factor (IGF)-I, which suggests that at least part of the growth-stimulating effects of milk occur through the stimulation of IGFs. Given that the biological purpose of milk is to support the newborn during a period of high growth velocity, such an effect seems plausible. Adding cow's milk to the diet of stunted children is likely to improve linear growth and thereby reduce morbidity. In well-nourished children, the long-term consequences of an increased consumption of cow's milk, which may lead to higher levels of IGF-I in circulation or an increase in the velocity of linear growth, are likely to be both positive and negative. Based on emerging data that suggest both growth and diet during early life program the IGF axis, the association between milk intake and later health is likely to be complex. [ Notice ]
Nutritional Epidemiology and Thyroid Hormone Metabolism
Authors: Vanderpas Jean
Published: April 2006

▪ Abstract  Severe iodine deficiency was the main cause of endemic goiter and cretinism. Most of the previously iodine-deficient areas are now supplemented, mainly with iodized salt. The geographical distribution of severe endemic areas has been progressively reduced, and at present, approximately 200 million people living in remote places are still at risk of severe iodine deficiency. International public health programs should be focused first on reaching these populations, and second on auditing and monitoring the operational work of supplementation programs. This second point is essential to prevent iodine-induced hyperthyroidism or interruptions of iodine supplement distribution, which could be catastrophic for the fetus and the young infant. Echography brings a complementary tool to clinical assessment of goiter by palpation. Inductively coupled plasma–mass spectrometry brings at least a definitive gold standard for iodine measurement and thyroid hormone measurement. Thiocyanate overload has been clearly documented as a goitrogen in Central Africa, and when associated with selenium deficiency, it may be included as risk factor for endemic myxedematous cretinism. Variable exposure to different environmental risk factors is likely the explanation of the variable distribution of two types of endemic cretinism (neurological and myxedematous), and the clinical overlap of the pathogeny of both syndromes is more important than previously described. It is possible that Kashin-Beck osteoarthropathy is another evanescent endemic disease that will disappear with the correction of iodine deficiency.
Cancer-Associated Cachexia and Underlying Biological Mechanisms
Authors: Baracos Vickie E.
Published: April 2006

▪ Abstract  Cancer metastases (spread to distant organs from the primary tumor site) signify systemic, progressive, and essentially incurable malignant disease. Anorexia and wasting develop continuously throughout the course of incurable cancer. Overall, in Westernized countries nearly exactly half of current cancer diagnoses end in cure and the other half end in death; thus, cancer-associated cachexia has a high prevalence. The pathophysiology of cancer-associated cachexia has two principal components: a failure of food intake and a systemic hypermetabolism/hypercatabolism syndrome. The superimposed metabolic changes result in a rate of depletion of physiological reserves of energy and protein that is greater than would be expected based on the prevailing level of food intake. These features indicate a need for nutritional support, metabolic management, and a clear appreciation of the context of life-limiting illness.
Choline: Critical Role During Fetal Development and Dietary Requirements in Adults
Authors: Zeisel Steven H.
Published: April 2006

▪ Abstract  Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.
Variations on a Gene: Rare and Common Variants in ABCA1 and Their Impact on HDL Cholesterol Levels and Atherosclerosis
Authors: Brunham Liam R. , Singaraja Roshni R. , Hayden Michael R.
Published: April 2006

▪ Abstract  Cholesterol and its metabolites play a variety of essential roles in living systems. Virtually all animal cells require cholesterol, which they acquire through synthesis or uptake, but only the liver can degrade cholesterol. The ABCA1 gene product regulates the rate-controlling step in the removal of cellular cholesterol: the efflux of cellular cholesterol and phospholipids to an apolipoprotein acceptor. Mutations in ABCA1, as seen in Tangier disease, result in accumulation of cellular cholesterol, reduced plasma high-density lipoprotein cholesterol, and increased risk for coronary artery disease. To date, more than 100 coding variants have been identified in ABCA1, and these variants result in a broad spectrum of biochemical and clinical phenotypes. Here we review genetic variation in ABCA1 and its critical role in cholesterol metabolism and atherosclerosis in the general population.
Immunonutrition in Surgery and Critical Care
Authors: Kudsk Kenneth A.
Published: April 2006

▪ Abstract  The benefits of specialty supplemented enteral diets administered to critically ill and critically injured patients and those undergoing major surgical procedures have been documented in a number of randomized prospective studies. It is unclear which nutrient or combination of nutrients causes the beneficial effects, but there are significant reductions in infectious complications depending upon the patient populations studied. It is imperative that the data be interpreted in the context of individual patient risk since specialty formulas appear most beneficial in patients at risk of subsequent complications or in those with significant pre-existing malnutrition. Although controversy exists regarding the use of specialty supplemented enteral diets in critically ill patients, they have been administered safely with minimal risk of adverse outcome in malnourished patients and in the critically ill and critically injured.
The Influence of Iron Status on Iodine Utilization and Thyroid Function
Authors: Zimmermann Michael B.
Published: April 2006

▪ Abstract  Despite significant progress, deficiencies of iron and iodine remain major public health problems affecting ≥30% of the global population. These deficiencies often coexist in children. Recent studies have demonstrated that a high prevalence of iron deficiency among children in areas of endemic goiter may reduce the effectiveness of iodized salt programs. These findings argue strongly for improving iron status in areas of overlapping deficiency, not only to combat anemia but also to increase the efficacy of iodine prophylaxis. The dual fortification of salt with iodine and iron may prove to be an effective and sustainable method to accomplish these important goals.
Fuel Metabolism in Starvation
Authors: Cahill George F.
Published: April 2006

▪ Abstract  This article, which is partly biographical and partly scientific, summarizes a life in academic medicine. It relates my progress from benchside to bedside and then to academic and research administration, and concludes with the teaching of human biology to college undergraduates. My experience as an intern (anno 1953) treating a youngster in diabetic ketoacidosis underscored our ignorance of the controls in human fuel metabolism. Circulating free fatty acids were then unknown, insulin could not be measured in biologic fluids, and β-hydroxybutyric acid, which was difficult to measure, was considered by many a metabolic poison. The central role of insulin and the metabolism of free fatty acids, glycerol, glucose, lactate, and pyruvate, combined with indirect calorimetry, needed characterization in a near-steady state, namely prolonged starvation. This is the main topic of this chapter. Due to its use by brain, D-β-hydroxybutyric acid not only has permitted man to survive prolonged starvation, but also may have therapeutic potential owing to its greater efficiency in providing cellular energy in ischemic states such as stroke, myocardial insufficiency, neonatal stress, genetic mitochondrial problems, and physical fatigue.
EXCITONS IN CONJUGATED OLIGOMER AGGREGATES, FILMS, AND CRYSTALS
Authors: Spano Frank C.
Published: April 2006

▪ Abstract  Recent experimental and theoretical investigations of excitons in conjugated oligomer nanoaggregates, thin films, and crystals are reviewed. The review focuses on the technologically important unsubstituted oligo-phenylene vinylenes (OPVn) and oligo-thiophenes (OTn), which exhibit side-by-side herringbone crystal packing. Many of the salient photophysical properties displayed by OPVn and OTn solid phases, including the large Davydov splitting, the rich variety of peaks due to vibronic coupling in both absorption and emission, and the unusual behavior of the emission origin, are accounted for in a model including excitonic coupling between molecules, linear exciton-phonon coupling, and disorder.
FEMTOSECOND TIME-RESOLVED PHOTOELECTRON IMAGING
Authors: Suzuki Toshinori
Published: April 2006

▪ Abstract  Femtosecond time-resolved photoelectron imaging (TRPEI) is a variant of time-resolved photoelectron spectroscopy used in the study of gas-phase photoinduced dynamics. A new observable, time-dependent photoionization-differential cross section provides useful information on wave-packet motions, electronic dephasing, and photoionization dynamics. This review describes fundamental issues and the most recent works involving TRPEI.
4D ULTRAFAST ELECTRON DIFFRACTION, CRYSTALLOGRAPHY, AND MICROSCOPY
Authors: Zewail Ahmed H.
Published: April 2006

▪ Abstract  In this review, we highlight the progress made in the development of 4D ultrafast electron diffraction (UED), crystallography (UEC), and microscopy (UEM) with a focus on concepts, methodologies, and prototypical applications. The joint atomic-scale resolutions in space and time, and sensitivity reached, make it possible to determine complex transient structures and assemblies in different phases. These applications include studies of isolated chemical reactions (molecular beams), interfaces, surfaces and nanocrystals, self-assembly, and 2D crystalline fatty-acid bilayers. In 4D UEM, we are now able, using timed, single-electron packets, to image nano-to-micro scale structures of materials and biological cells. Future applications of these methods are foreseen across areas of physics, chemistry, and biology.
Evolution of Plant Pathogenicity in Streptomyces
Authors: Loria Rosemary , Kers Johan , Joshi Madhumita
Published: April 2006

Abstract  Among the multitude of soil-inhabiting, saprophytic Streptomyces species are a growing number of plant pathogens that cause economically important diseases, including potato scab. Streptomyces scabies is the dominant pathogenic species worldwide, but is only one of many that cause very similar disease symptoms on plants. Molecular genetic analysis is beginning to identify the mechanisms used by plant pathogenic species to manipulate their hosts. The nitrated dipeptide phytotoxin, thaxtomin, inhibits cellulose biosynthesis in expanding plant tissues, stimulates Ca2+ spiking, and causes cell death. A secreted necrogenic protein, Nec1, contributes to virulence on diverse plant species. The thaxtomin biosynthetic genes and nec1 lie on a large mobilizable PAI, along with other putative virulence genes including a cytokinin biosynthetic pathway and a saponinase homolog. The PAI is mobilized during conjugation and site-specifically inserts in the linear chromosome of recipient species, accounting for the emergence of new pathogens in agricultural systems. The recently available genome sequence of S. scabies will accelerate research on host-pathogen interactions.
Noel T. Keen—Pioneer Leader in Molecular Plant Pathology
Authors: Collmer Alan , Gold Scott
Published: April 2006

Noel T. Keen (1940–2002) made pioneering contributions to molecular plant pathology during a period when the study of disease mechanisms was transformed by the new tools of molecular genetics. His primary contributions involved race-specific elicitors of plant defenses and bacterial pectic enzymes. In collaboration with Brian J. Staskawicz and Frances Jurnak, respectively, Noel cloned the first avirulence gene and determined that pectate lyase C possessed a novel structural motif, known as the parallel β-helix. Noel received his B.S. and M.S. from Iowa State University in Ames and his Ph.D. from the Department of Plant Pathology at the University of Wisconsin in Madison in 1968. He joined the faculty of the Department of Plant Pathology at the University of California at Riverside the same year and remained there his entire career. He served as Chair of the department from 1983 to 1989 and in 1997 assumed the William and Sue Johnson Endowed Chair in Molecular Plant Pathology. He became a Fellow of the American Phytopathological Society in 1991, a Fellow of the American Association for the Advancement of Science in 1996, a Fellow of the American Academy of Microbiology in 1997, and a member of the National Academy of Sciences in 1997. He was serving as President of the American Phytopathological Society (2001–2002) at the time of his death.
Long-Distance RNA-RNA Interactions in Plant Virus Gene Expression and Replication
Authors: Miller W. Allen , White K. Andrew
Published: April 2006

Abstract  The vast majority of plant and animal viruses have RNA genomes. Viral gene expression and replication are controlled by cis-acting elements in the viral genome, which have been viewed conventionally as localized structures. However, recent research has altered this perception and provided compelling evidence for cooperative activity involving distantly positioned RNA elements. This chapter focuses on viral RNA elements that interact across hundreds or thousands of intervening nucleotides to control translation, genomic RNA synthesis, and subgenomic mRNA transcription. We discuss evidence supporting the existence and function of the interactions, and speculate on the regulatory roles that such long-distance interactions play in the virus life cycle. We emphasize viruses in the Tombusviridae and Luteoviridae families in which long-distance interactions are best characterized, but similar phenomena in other viruses are also discussed. Many more examples likely remain undiscovered.
Fitness of Human Enteric Pathogens on Plants and Implications for Food Safety
Authors: Brandl Maria T.
Published: April 2006

Abstract  The continuous rise in the number of outbreaks of foodborne illness linked to fresh fruit and vegetables challenges the notion that enteric pathogens are defined mostly by their ability to colonize the intestinal habitat. This review describes the epidemiology of produce-associated outbreaks of foodborne disease and presents recently acquired knowledge about the behavior of enteric pathogens on plants, with an emphasis on Salmonella enterica, Escherichia coli O157:H7, and Listeria monocytogenes. The growth and survival of enteric pathogens on plants are discussed in the light of knowledge and concepts in plant microbial ecology, including epiphytic fitness, the physicochemical nature of plant surfaces, biofilm formation, and microbe-microbe and plant-microbe interactions. Information regarding the various stresses that affect the survival of enteric pathogens and the molecular events that underlie their interactions in the plant environment provides a good foundation for assessing their role in the infectious dose of the pathogens when contaminated fresh produce is the vehicle of illness.
Biology of Flower-Infecting Fungi
Authors: Ngugi Henry K. , Scherm Harald
Published: April 2006

Abstract  The ability to infect host flowers offers important ecological benefits to plant-parasitic fungi; not surprisingly, therefore, numerous fungal species from a wide range of taxonomic groups have adopted a life style that involves flower infection. Although flower-infecting fungi are very diverse, they can be classified readily into three major groups: opportunistic, unspecialized pathogens causing necrotic symptoms such as blossom blights (group 1), and specialist flower pathogens which infect inflorescences either through the gynoecium (group 2) or systemically through the apical meristem (group 3). This three-tier system is supported by life history attributes such as host range, mode of spore transmission, degree of host sterilization as a result of infection, and whether or not the fungus undergoes an obligate sexual cycle, produces resting spores in affected inflorescences, and is r- or K-selected. Across the three groups, the flower as an infection court poses important challenges for disease management. Ecologically and evolutionarily, terms and concepts borrowed from the study of venereal (sexually transmitted) diseases of animals do not adequately capture the range of strategies employed by fungi that infect flowers.
Coexistence of Related Pathogen Species on Arable Crops in Space and Time
Authors: Fitt Bruce D.L. , Huang Yong-Ju , Bosch Frank van den , West Jonathan S.
Published: April 2006

Abstract  This review considers factors affecting the coexistence of closely related pathogen species on arable crops, with particular reference to data available at Rothamsted for Septoria tritici/Stagonospora nodorum (Mycosphaerella graminicola/Phaeosphaeria nodorum) (septoria leaf blotch diseases on winter wheat), Oculimacula yallundae/O. acuformis (eyespot disease of winter cereals), and Leptosphaeria maculans/L. biglobosa (phoma stem canker on winter oilseed rape). Factors affecting the short-term, medium-term, and long-term coexistence of such related pathogen species are reviewed, and their evolution from common ancestors considered. Small niche differences between the related pathogen species enable them to coexist on the same host. The niche differences result from small differences in their biology/epidemiology, leading to separation in space, time, or resource use. Changes in both natural (e.g., fluctuating temperature) and man-made (e.g., agronomic practices, pollution) factors influence the coexistence. Such factors may result in coexistence between the related species in some parts of the world, whereas in other parts only one species occurs. These principles illustrated with pathogens of arable crops are generic to other host-pathogen systems.
Climate Change Effects on Plant Disease: Genomes to Ecosystems
Authors: Garrett K. A. , Dendy S. P. , Frank E. E. , Rouse M. N. , Travers S. E.
Published: April 2006

Abstract  Research in the effects of climate change on plant disease continues to be limited, but some striking progress has been made. At the genomic level, advances in technologies for the high-throughput analysis of gene expression have made it possible to begin discriminating responses to different biotic and abiotic stressors and potential trade-offs in responses. At the scale of the individual plant, enough experiments have been performed to begin synthesizing the effects of climate variables on infection rates, though pathosystem-specific characteristics make synthesis challenging. Models of plant disease have now been developed to incorporate more sophisticated climate predictions. At the population level, the adaptive potential of plant and pathogen populations may prove to be one of the most important predictors of the magnitude of climate change effects. Ecosystem ecologists are now addressing the role of plant disease in ecosystem processes and the challenge of scaling up from individual infection probabilities to epidemics and broader impacts.
Significance of Inducible Defense-related Proteins in Infected Plants
Authors: van Loon L.C. , Rep M. , Pieterse C.M.J.
Published: April 2006

Abstract  Inducible defense-related proteins have been described in many plant species upon infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several types of proteins are common and have been classified into 17 families of pathogenesis-related proteins (PRs). Others have so far been found to occur more specifically in some plant species. Most PRs and related proteins are induced through the action of the signaling compounds salicylic acid, jasmonic acid, or ethylene, and possess antimicrobial activities in vitro through hydrolytic activities on cell walls, contact toxicity, and perhaps an involvement in defense signaling. However, when expressed in transgenic plants, they reduce only a limited number of diseases, depending on the nature of the protein, plant species, and pathogen involved. As exemplified by the PR-1 proteins in Arabidopsis and rice, many homologous proteins belonging to the same family are regulated developmentally and may serve different functions in specific organs or tissues. Several defense-related proteins are induced during senescence, wounding or cold stress, and some possess antifreeze activity. Many defense-related proteins are present constitutively in floral tissues and a substantial number of PR-like proteins in pollen, fruits, and vegetables can provoke allergy in humans. The evolutionary conservation of similar defense-related proteins in monocots and dicots, but also their divergent occurrence in other conditions, suggest that these proteins serve essential functions in plant life, whether in defense or not.
Molecular Ecology and Emergence of Tropical Plant Viruses
Authors: Fargette D. , Konaté G. , Fauquet C. , Muller E. , Peterschmitt M. , Thresh J.M.
Published: April 2006

Abstract  An appreciation of the risks caused by emergent plant viruses is critical in tropical areas that rely heavily on agriculture for subsistence and rural livelihood. Molecular ecology, within 10 years, has unraveled the factors responsible for the emergence of several of the economically most important tropical plant viruses: Rice yellow mottle virus (RYMV), Cassava mosaic geminiviruses (CMGs), Maize streak virus (MSV), and Banana streak virus (BSV). A large range of mechanisms—most unsuspected until recently—were involved: recombination and synergism between virus species, new vector biotypes, genome integration of the virus, host adaptation, and long-distance dispersal. A complex chain of molecular and ecological events resulted in novel virus-vector-plant-environment interactions that led to virus emergence. It invariably involved a major agricultural change: crop introduction, cultural intensification, germplasm movement, and new genotypes. A current challenge is now to complement the analysis of the causes by an assessment of the risks of emergence. Recent attempts to assess the risks of emergence of virulent virus strains are described.
PLATONIC QUANDARIES: Recent Scholarship on Plato
Authors: Allen Danielle
Published: April 2006

▪ Abstract  Recent scholarship on Plato falls into three categories: Straussian readings, Socratic readings, and the readings of the Chastened Utopians. The first group follows Strauss in reaffirming that Plato saw human nature as unchangeable and human political possibilities as relatively limited; on this account, the Republic is a joke that argues against all utopian projects. The second group focuses on Socrates rather than Plato, directing attention primarily toward individual self-fashioning that may or may not have political effects. The third group sees Plato as having believed in the possibility of political change and as having sought to intervene in the politics of his day. The central issue contested by these different schools of thought is whether human nature is malleable; specific issues of gender and militarism arise repeatedly in the discussion of this question.
NEW MACROECONOMICS AND POLITICAL SCIENCE
Authors: Iversen Torben , Soskice David
Published: April 2006

▪ Abstract  We review the use of macroeconomics in political science over the past 40 years. The field has been dominated by new classical theory, which leaves little room for economic policy and focuses attention on what democratic governments can do wrong in the short term. The resulting literatures on political business cycles and central bank independence are large and sophisticated, but they fail, we argue, to account for most of the observed variance in economic policies and outcomes. In the past decade, mainstream macroeconomics has moved away from new classical approaches toward New Keynesian theories with greater scope for macroeconomic policy. These new approaches, with little impact so far in political science, are reviewed and their implications drawn out. Instead of explaining short-sighted government behavior in an economy with little scope for economic policy, the key question for political science may be why governments often pursue longer-run objectives in an economy with considerable scope for economic policy.
FOREIGN POLICY AND THE ELECTORAL CONNECTION
Authors: Aldrich John H. , Gelpi Christopher , Feaver Peter , Reifler Jason , Sharp Kristin Thompson
Published: April 2006

▪ Abstract  Public opinion is central to representation, democratic accountability, and decision making. Yet, the public was long believed to be relatively uninterested in foreign affairs, absent an immediate threat to safety and welfare. It had become conventional to say that “voting ends at water's edge.” We start the examination of the scholarly understanding of the role of foreign affairs in public opinion and voting at that low point of view. Much subsequent development saw an increasing degree of holding and using of attitudes and beliefs about foreign affairs among the public. Moving in parallel with developments in political psychology, theoretical and methodological advances led to an increasingly widely shared view that the public holds reasonably sensible and nuanced views, that these help shape their political behaviors, and that these, in turn, help shape and constrain foreign policy making.
Low Fertility at the Turn of the Twenty-First Century
Authors: Morgan S. Philip , Taylor Miles G.
Published: April 2006

In the past few decades, demographic concerns have shifted from rapid population growth fueled by high fertility to concerns of population decline produced by very low, sub-replacement fertility levels. Once considered a problem unique to Europe or developed nations, concerns now center on the global spread of low fertility. Nearly half of the world's population now lives in countries with fertility at or below replacement levels. Further, by the mid-twenty-first century three of four countries now described as developing are projected to reach or slip below replacement fertility. We review the research on low fertility through the predominant frameworks and theories used to explain it. These explanations range from decomposition and proximate determinant frameworks to grand theories on the fundamental causes underlying the pervasiveness and spread of low fertility. We focus on the ability of theory to situate previous and future findings and conclude with directions for furthur research.
Legitimacy as a Social Process
Authors: Johnson Cathryn , Dowd Timothy J. , Ridgeway Cecilia L.
Published: April 2006

To gain an in-depth understanding of legitimacy as a general social process, we review contemporary approaches to legitimacy within two areas of sociology: social psychology and organizations. A comparison of these distinct approaches allows us to explain the process, both in implicit and explicit ways at different levels of analysis, through which a social object is construed as legitimate. This comparison also suggests four stages in the process by which new social objects, both individual (worthy/unworthy individuals) and collective (organizational forms), gain legitimation: innovation, local validation, diffusion, and general validation. We then show how legitimation of the status quo—that is, the acceptance of widespread consensual schemas/beliefs in the larger society—often fosters the stability of nonoptimal actions and practices that are created as a result of these new individual and collective social objects. Finally, we discuss how consensual beliefs such as status beliefs and cultural capital fuel the reproduction of inefficiency and inequality in groups and organizations.
Law and the American State
Authors: Skrentny John D.
Published: April 2006

Although classical theories of the state and key texts of historical institutionalism and American political development (APD) defined the American state as a fundamentally legal entity, contemporary studies of the American state show a range of roles for law and courts, from no role at all, to a constraint or obstacle, to a positive force for state development. This review maps these varying roles, showing that law and courts are most absent or play negative roles in studies of the growth of the national administrative welfare state. It highlights new studies in this area that show the American state as a legal state and surveys growing numbers of historical institutionalist and APD studies of the state and economic and social regulation, where law and courts are more prominent. It points to the important but mostly neglected subjects of criminal and tort law as areas for future study that unite law and the state. Finally, it concludes by showing how concepts from the sociology of law—legal mobilization, law/court effectiveness, and legal consciousness—can inform state-centered political studies. Portraying the American state as a legal state yields a richer conception, reveals new and important subject matter and explanatory strategies, and can encourage dialogue between scholars of law and scholars of the state.
The Science of Human Rights, War Crimes, and Humanitarian Emergencies
Authors: Hagan John , Schoenfeld Heather , Palloni Alberto
Published: April 2006

Sociology can be an important disciplinary bridge between the study of what demographers call forced migration and mortality and what legal sociologists and criminologists understand as war crimes. The challenge is to develop a critically informed sociological synthesis that joins our understanding of the frequently politicized health and violence dimensions of what are also diplomatically called “complex” humanitarian emergencies. The frequency of these emergencies is growing, and there is an increasing amount of data collected by governmental and nongovernmental organizations exposing large-scale violations of human rights and war crimes. Yet analyses of these data are often inadequate. Although the humanitarian emergency in Kosovo marked a high point in collaborative human rights research, the circumstances that allowed this collaboration are probably atypical. We consider how, in increasingly challenging circumstances such as the Darfur region of Sudan, population health and legal and criminological surveys can be joined to provide more comprehensive estimates of deaths resulting from violent attacks as well as from disease and starvation. The discipline of sociology, with its expertise in population-based surveys and other measurement and analytic techniques, has the capacity to bridge differences and to provide more meaningfully synthesized conclusions.
Community Ecology and the Sociology of Organizations
Authors: Freeman John H. , Audia Pino G.
Published: April 2006

Research on organizations is increasingly informed by analysis of community context. Community can be conceptualized as sets of relations between organizational forms or as places where organizations are located in resource space or in geography. In both modes, organizations operate interdependently with social institutions and with other units of social structure. Because such relationships channel flows of resources, opportunities are granted or withheld from social actors depending in part on their organization connections. Such considerations encourage analyses of organizations in ways that spread the relevance of results beyond organizationally defined research problem areas.
Organizational Restructuring and its Consequences: Rhetorical and Structural
Authors: Hirsch Paul M. , Soucey Michaela De
Published: April 2006

In this review, we examine the idea of organizational restructuring as a conceptual tool and how it has been used to alter societal definitions and interpretations of employment. Although use of the term restructuring is relatively recent, the broad issue of changing employment conditions with which it is concerned has a long history, going back to the industrial revolution. Our main focus is a consideration of the causes and consequences of restructuring, in its more recent rhetorical and structural versions. In their pursuit of greater efficiencies, organizations adapt to the demands of increasingly global markets, and these adaptations are crucial components of what is popularly referred to as the new economy. Such developments are applauded in most economic theory, but sociologists examine both sides of their social impact, including the adverse effects and implications of such externalities as the social disruptions caused by downsizing and other organizational and corporate changes. These studies provide important contributions to our knowledge of how much, and when, promises of organizational efficiency are in fact deliverable and responsive to those affected by them. We argue that the language of restructuring is regularly used to mask, reframe, and sugarcoat economic slumps as possessing positive social outcomes. We conclude by positioning restructuring as an important component of the current American export of managerial ideology to transnational contexts and suggest further examination of how restructuring affects the culture of business in these other national contexts.
Problems and Prospects in the Study of Physician-Patient Interaction: 30 Years of Research
Authors: Heritage John , Maynard Douglas W.
Published: April 2006

Working within the functionalist perspective that he did so much to develop, Parsons (1951) conceptualized the physician-patient relationship according to a normative framework defined by the pattern variable scheme. As Parsons clearly recognized, this normative conceptualization was one that empirical reality at best only approximates. In the 1970s, two major studies established doctor-patient interaction as a viable research domain. In the present review, we consider approaches to the medical interview developing from these initiatives and that have a primary focus on observable features of doctor-patient interaction. Within this orientation, we consider literature dealing with social, moral, and technical dilemmas that physicians and patients face in primary care and the resources that they deploy in solving them. This literature embodies a steady evolution away from a doctor-centered emphasis toward a more balanced focus on the conduct of doctors and patients together.
Melanin-concentrating hormone stimulates human growth hormone secretion: a novel effect of MCH on the hypothalamic-pituitary axis
Authors: Segal-Lieberman Gabriella , Rubinfeld Hadara , Glick Moran , Kronfeld-Schor Noga , Shimon Ilan
Published: April 2006

Melanin-concentrating hormone (MCH), a 19-amino acid orexigenic (appetite-stimulating) hypothalamic peptide, is an important regulator of energy homeostasis. It is cleaved from its precursor prepro-MCH (ppMCH) along with several other neuropeptides whose roles are not fully defined. Because pituitary hormones such as growth hormone (GH), ACTH, and thyroid-stimulating hormone affect body weight and composition, appetite, insulin sensitivity, and lipoprotein metabolism, we investigated whether MCH exerts direct effects on the human pituitary to regulate energy balance using dispersed human fetal pituitaries (21–22 wk gestation) and cultured GH-secreting adenomas. We found that MCH receptor-1 (MCH-R1), but not MCH receptor-2, is expressed in both normal (fetal and adult) human pituitary tissues and in GH cell adenomas. MCH (10 nM) stimulated GH release from human fetal pituitary cultures by up to 62% during a 4-h incubation ( P < 0.05). Interestingly, neuropeptide EI (10 nM), which is also cleaved from ppMCH, increased human GH secretion by up to 124% in fetal pituitaries. A milder, albeit significant, induction of GH secretion by MCH (20%) was seen in cultured GH-secreting pituitary adenomas. A comparable stimulation of GH secretion was seen when cultured mouse pituitary cells were treated with MCH. Treatment of cultured GH adenoma cells with MCH (100 nM) induced extracellular signal-regulated kinases 1 and 2 phosphorylation, suggesting activation of MCH-R1. In aggregate, these data suggest that MCH may regulate pituitary GH secretion and imply a potential cross-talk mechanism between appetite-regulating neuropeptides and pituitary hormones.
Effects of calcium-sensing receptor on the secretion of parathyroid hormone-related peptide and its impact on humoral hypercalcemia of malignancy
Authors: Chattopadhyay Naibedya
Published: April 2006

The extracellular calcium-sensing receptor (CaR) plays a key role in the defense against hypercalcemia by “sensing” extracellular calcium (Ca2+o) levels in the parathyroid and kidney, the key organs maintaining systemic calcium homeostasis. However, CaR function can be aberrant in certain pathophysiological states, e.g., in some types of cancers known to produce humoral hypercalcemia of malignancy (HHM) in humans and animal models in which high Ca2+o, via the CaR, produces a homeostatically inappropriate stimulation of parathyroid hormone-related peptide (PTHrP) secretion from these tumors. Increased levels of PTHrP set a cycle in motion whereby elevated systemic levels of Ca2+oresulting from its increased bone-resorptive and positive renal calcium-reabsorbing effects give rise to hypercalcemia, which in turn begets worsening hypercalcemia by stimulating further release of PTHrP by the cancer cells. I review the relationship between CaR activation and PTHrP release in normal and tumor cells giving rise to HHM and/or malignant osteolysis and the actions of the receptor on key cellular events such as proliferation, angiogenesis, and apoptosis of cancer cells that will favor tumor growth and osseous metastasis. I also illustrate diverse signaling mechanisms underlying CaR-stimulated PTHrP secretion and other cellular events in tumor cells. Finally, I raise several necessary questions to demonstrate the roles of the receptor in promoting tumors and metastases that will enable consideration of the CaR as a potential antagonizing/neutralizing target for the treatment of HHM.
The molecular mechanism of EGF receptor activation in pancreatic β-cells by thyrotropin-releasing hormone
Authors: Luo LuGuang , Yano Naohiro , Luo John Z. Q.
Published: April 2006

Thyrotropin-releasing hormone (TRH) and its receptor subtype TRH receptor-1 (TRHR1) are found in pancreatic β-cells, and it has been shown that TRH might have potential for autocrine/paracrine regulation through the TRHR1 receptor. In this paper, TRHR1 is studied to find whether it can initiate multiple signal transduction pathways to activate the epidermal growth factor (EGF) receptor in pancreatic β-cells. By initiating TRHR1 G protein-coupled receptor (GPCR) and dissociated αβγ-complex, TRH (200 nM) activates tyrosine residues at Tyr845(a known target for Src) and Tyr1068in the EGF receptor complex of an immortalized mouse β-cell line, βTC-6. Through manipulating the activation of Src, PKC, and heparin-binding EGF-like growth factor (HB-EGF), with corresponding individual inhibitors and activators, multiple signal transduction pathways linking TRH to EGF receptors in βTC-6 cell line have been revealed. The pathways include the activation of Src kinase and the release of HB-EGF as a consequence of matrix metalloproteinase (MMP)-3 activation. Alternatively, TRH inhibited PKC activity by reducing the EGF receptor serine/threonine phosphorylation, thereby enhancing tyrosine phosphorylation. TRH receptor activation of Src may have a central role in mediating the effects of TRH on the EGF receptor. The activation of the EGF receptor by TRH in multiple circumstances may have important implications for pancreatic β-cell biology.
Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state
Authors: Abraldes Juan G. , Iwakiri Yasuko , Loureiro-Silva Mauricio , Haq Omar , Sessa William C. , Groszmann Roberto J.
Published: April 2006

Increased nitric oxide (NO) is the main factor leading to the hyperdynamic circulation associated with advanced portal hypertension (PHT), but the initial mechanisms and the magnitude of increase in portal pressure required to trigger NO production are not known. We addressed these issues by studying systemic and splanchnic hemodynamics and endothelial NO synthase (eNOS) and VEGF expression in rats with different degrees of portal hypertension. Portal vein ligation (PVL) performed over needles of three different calibers (16-, 18-, and 20-gauge) yielded different degrees of PHT and portosystemic shunting. Compared with sham rats, all three groups of PVL rats exhibited features of hyperdynamic circulation. Rats with minimal portal hypertension (PVL with a 16-gauge needle) showed an early increase in VEGF and eNOS expression selectively at the jejunum. Immunofluorescence showed that VEGF expression was located in highly vascularized areas of the mucosa. Inhibition of VEGF signaling markedly attenuated the increase in eNOS expression. In conclusion, mild increases in portal pressure are enough to upregulate eNOS at the intestinal microcirculation, and this occurs, at least in part, through VEGF upregulation.
Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4
Authors: Xiang Fan , Sakata Yasuhiko , Cui Lei , Youngblood Joey M. , Nakagami Hironori , Liao James K. , Liao Ronglih , Chin Michael T.
Published: April 2006

Pathological cardiac hypertrophy is considered a precursor to clinical heart failure. Understanding the transcriptional regulators that suppress the hypertrophic response may have profound implications for the treatment of heart disease. We report the generation of transgenic mice that overexpress the transcription factor CHF1/Hey2 in the myocardium. In response to the α-adrenergic agonist phenylephrine, they show marked attenuation in the hypertrophic response compared with wild-type controls, even though blood pressure is similar in both groups. Isolated myocytes from transgenic mice demonstrate a similar resistance to phenylephrine-induced hypertrophy in vitro, providing further evidence that the protective effect of CHF1/Hey2 is mediated at the myocyte level. Induction of the hypertrophy marker genes ANF, BNP, and β- MHC in the transgenic cells is concurrently suppressed in vivo and in vitro, demonstrating that the induction of hypertrophy-associated genes is repressed by CHF1/Hey2. Transfection of CHF1/Hey2 into neonatal cardiomyocytes suppresses activation of an ANF reporter plasmid by the transcription factor GATA4, which has previously been shown to activate a hypertrophic transcriptional program. Furthermore, CHF1/Hey2 binds GATA4 directly in coimmunoprecipitation assays and inhibits the binding of GATA4 to its recognition sequence within the ANF promoter. Our findings demonstrate that CHF1/Hey2 functions as an antihypertrophic gene, possibly through inhibition of a GATA4-dependent hypertrophic program.
Involvement of cyclooxygenase-2 and prostaglandins in the molecular pathogenesis of inflammatory lung diseases
Authors: Park Gye Young , Christman John W.
Published: April 2006

Inducible cyclooxygenase (COX-2) and its metabolites have diverse and potent biological actions that are important for both physiological and disease states of lung. The wide variety of prostaglandin (PG) products are influenced by the level of cellular activation, the exact nature of the stimulus, and the specific cell type involved in their production. In turn, the anti- and proinflammatory response of PG is mediated by a blend of specific surface and intracellular receptors that mediate diverse cellular events. The complexity of this system is being at least partially resolved by the generation of specific molecular biological research tools that include cloning and characterization of the enzymes distal to COX-2 and the corresponding receptors to the final cellular products of arachidonic metabolism. The most informative of these approaches have employed genetically modified animals and specific receptor antagonists to determine the exact role of specific COX-2-derived metabolites on specific cell types of the lung in the context of inflammatory models. These data have suggested a number of cell-specific, pathway-specific, and receptor-specific approaches that could lead to effective therapeutic interventions for most inflammatory lung diseases.