bluuebunny/crossref_metadata_2025 huggingface dataset:
BIOMECHANICAL AND MOLECULAR REGULATION OF BONE REMODELING
Authors: Robling Alexander G. , Castillo Alesha B. , Turner Charles H.
Published: April 2006

Bone is a dynamic tissue that is constantly renewed. The cell populations that participate in this process—the osteoblasts and osteoclasts—are derived from different progenitor pools that are under distinct molecular control mechanisms. Together, these cells form temporary anatomical structures, called basic multicellular units, that execute bone remodeling. A number of stimuli affect bone turnover, including hormones, cytokines, and mechanical stimuli. All of these factors affect the amount and quality of the tissue produced. Mechanical loading is a particularly potent stimulus for bone cells, which improves bone strength and inhibits bone loss with age. Like other materials, bone accumulates damage from loading, but, unlike engineering materials, bone is capable of self-repair. The molecular mechanisms by which bone adapts to loading and repairs damage are starting to become clear. Many of these processes have implications for bone health, disease, and the feasibility of living in weightless environments (e.g., spaceflight).
ELECTRICAL FORCES FOR MICROSCALE CELL MANIPULATION
Authors: Voldman Joel
Published: April 2006

Electrical forces for manipulating cells at the microscale include electrophoresis and dielectrophoresis. Electrophoretic forces arise from the interaction of a cell's charge and an electric field, whereas dielectrophoresis arises from a cell's polarizability. Both forces can be used to create microsystems that separate cell mixtures into its component cell types or act as electrical “handles” to transport cells or place them in specific locations. This review explores the use of these two forces for microscale cell manipulation. We first examine the forces and electrodes used to create them, then address potential impacts on cell health, followed by examples of devices for both separating cells and handling them.
Machine Learning for Detection and Diagnosis of Disease
Authors: Sajda Paul
Published: April 2006

Machine learning offers a principled approach for developing sophisticated, automatic, and objective algorithms for analysis of high-dimensional and multimodal biomedical data. This review focuses on several advances in the state of the art that have shown promise in improving detection, diagnosis, and therapeutic monitoring of disease. Key in the advancement has been the development of a more in-depth understanding and theoretical analysis of critical issues related to algorithmic construction and learning theory. These include trade-offs for maximizing generalization performance, use of physically realistic constraints, and incorporation of prior knowledge and uncertainty. The review describes recent developments in machine learning, focusing on supervised and unsupervised linear methods and Bayesian inference, which have made significant impacts in the detection and diagnosis of disease in biomedicine. We describe the different methodologies and, for each, provide examples of their application to specific domains in biomedical diagnostics.
Ultrasound Microbubble Contrast Agents: Fundamentals and Application to Gene and Drug Delivery
Authors: Ferrara Katherine , Pollard Rachel , Borden Mark
Published: April 2006

This review offers a critical analysis of the state of the art of medical microbubbles and their application in therapeutic delivery and monitoring. When driven by an ultrasonic pulse, these small gas bubbles oscillate with a wall velocity on the order of tens to hundreds of meters per second and can be deflected to a vessel wall or fragmented into particles on the order of nanometers. While single-session molecular imaging of multiple targets is difficult with affinity-based strategies employed in some other imaging modalities, microbubble fragmentation facilitates such studies. Similarly, a focused ultrasound beam can be used to disrupt delivery vehicles and blood vessel walls, offering the opportunity to locally deliver a drug or gene. Clinical translation of these vehicles will require that current challenges be overcome, where these challenges include rapid clearance and low payload. The technology, early successes with drug and gene delivery, and potential clinical applications are reviewed.
EVOLUTIONARY RELATIONSHIPS AND STRUCTURAL MECHANISMS OF AAA+ PROTEINS
Authors: Erzberger Jan P. , Berger James M.
Published: April 2006

Complex cellular events commonly depend on the activity of molecular “machines” that efficiently couple enzymatic and regulatory functions within a multiprotein assembly. An essential and expanding subset of these assemblies comprises proteins of the ATPases associated with diverse cellular activities (AAA+) family. The defining feature of AAA+ proteins is a structurally conserved ATP-binding module that oligomerizes into active arrays. ATP binding and hydrolysis events at the interface of neighboring subunits drive conformational changes within the AAA+ assembly that direct translocation or remodeling of target substrates. In this review, we describe the critical features of the AAA+ domain, summarize our current knowledge of how this versatile element is incorporated into larger assemblies, and discuss specific adaptations of the AAA+ fold that allow complex molecular manipulations to be carried out for a highly diverse set of macromolecular targets.
CONTINUOUS MEMBRANE-CYTOSKELETON ADHESION REQUIRES CONTINUOUS ACCOMMODATION TO LIPID AND CYTOSKELETON DYNAMICS
Authors: Sheetz Michael P. , Sable Julia E. , Döbereiner Hans-Günther
Published: April 2006

The plasma membrane of most animal cells conforms to the cytoskeleton and only occasionally separates to form blebs. Previous studies indicated that many weak interactions between cytoskeleton and the lipid bilayer kept the surfaces together to counteract the normal outward pressure of cytoplasm. Either the loss of adhesion strength or the formation of gaps in the cytoskeleton enables the pressure to form blebs. Membrane-associated cytoskeleton proteins, such as spectrin and filamin, can control the movement and aggregation of membrane proteins and lipids, e.g., phosphoinositol phospholipids (PIPs), as well as blebbing. At the same time, lipids (particularly PIPs) and membrane proteins affect cytoskeleton and signaling dynamics. We consider here the roles of the major phosphatidylinositol-4,5-diphosphate (PIP2) binding protein, MARCKS, and PIP2 levels in controlling cytoskeleton dynamics. Further understanding of dynamics will provide important clues about how membrane-cytoskeleton adhesion rapidly adjusts to cytoskeleton and membrane dynamics.
RADIOLYTIC PROTEIN FOOTPRINTING WITH MASS SPECTROMETRY TO PROBE THE STRUCTURE OF MACROMOLECULAR COMPLEXES
Authors: Takamoto Keiji , Chance Mark R.
Published: April 2006

Structural proteomics approaches using mass spectrometry are increasingly used in biology to examine the composition and structure of macromolecules. Hydroxyl radical–mediated protein footprinting using mass spectrometry has recently been developed to define structure, assembly, and conformational changes of macromolecules in solution based on measurements of reactivity of amino acid side chain groups with covalent modification reagents. Accurate measurements of side chain reactivity are achieved using quantitative liquid-chromatography-coupled mass spectrometry, whereas the side chain modification sites are identified using tandem mass spectrometry. In addition, the use of footprinting data in conjunction with computational modeling approaches is a powerful new method for testing and refining structural models of macromolecules and their complexes. In this review, we discuss the basic chemistry of hydroxyl radical reactions with peptides and proteins, highlight various approaches to map protein structure using radical oxidation methods, and describe state-of-the-art approaches to combine computational and footprinting data.
WATER MEDIATION IN PROTEIN FOLDING AND MOLECULAR RECOGNITION
Authors: Levy Yaakov , Onuchic José N.
Published: April 2006

Water is essential for life in many ways, and without it biomolecules might no longer truly be biomolecules. In particular, water is important to the structure, stability, dynamics, and function of biological macromolecules. In protein folding, water mediates the collapse of the chain and the search for the native topology through a funneled energy landscape. Water actively participates in molecular recognition by mediating the interactions between binding partners and contributes to either enthalpic or entropic stabilization. Accordingly, water must be included in recognition and structure prediction codes to capture specificity. Thus water should not be treated as an inert environment, but rather as an integral and active component of biomolecular systems, where it has both dynamic and structural roles. Focusing on water sheds light on the physics and function of biological machinery and self-assembly and may advance our understanding of the natural design of proteins and nucleic acids.
TIN-BASED GROUP IV SEMICONDUCTORS: New Platforms for Opto- and Microelectronics on Silicon
Authors: Kouvetakis J. , Menendez J. , Chizmeshya A.V.G.
Published: April 2006

▪ Abstract  New classes of Sn-containing group IV semiconductors are described. Novel CVD routes lead to growth of a broad range of Ge1−ySny alloys and compounds directly on Si substrates. The direct bandgap (E0) and optical transitions E0+Δ0, E1, E1+Δ1, E0′, and E2 of Ge1−ySny exhibit strong nonlinearities in the compositional dependence, and their bowing parameters correlate with those in Ge1 −xSix, suggesting a scaling behavior for the electronic properties. The Ge1−ySny films can be used as “virtual substrates” for the subsequent growth of Ge1−x−ySixSny ternaries. These are created for the first time and exhibit unprecedented thermal stability, superior crystallinity and unique optical and strain properties such as adjustable bandgaps, and controllable strain states (compressive, relaxed, and tensile). The synthesis of Ge1−x−ySixSny makes it possible to decouple strain and bandgap and adds new levels of flexibility to the design of group IV devices. The Ge-Si-Sn system also represents a new class of “designer” templates for the monolithic integration of III-V and II-VI semiconductors with Si electronics.
POSITRON ANNIHILATION AS A METHOD TO CHARACTERIZE POROUS MATERIALS
Authors: Gidley David W. , Peng Hua-Gen , Vallery Richard S.
Published: April 2006

▪ Abstract  Beam-based positron annihilation spectroscopy (PAS) is a powerful porosimetry technique with broad applicability in the characterization of nanoporous thin films, especially insulators. Pore sizes and distributions in the 0.3–30 nm range are nondestructively determined with only the implantation of low-energy positrons from a table-top beam. Depth-profiling with PAS has proven to be an ideal way to measure the interconnection length of pores, search for depth-dependent inhomogeneities or damage in the pore structure, and explore porosity hidden beneath dense layers or diffusion barriers. The capability of PAS is rapidly maturing as new intense positron beams around the globe spawn more accessible PAS facilities. After a short primer on the physics of positrons in insulators, the various probe techniques of PAS are briefly summarized, followed by a more detailed discussion of the wide range of nanoporous film parameters that PAS can characterize.
PROGRESS IN MICROSTRUCTURED OPTICAL FIBERS
Authors: Monro Tanya M. , Ebendorff-Heidepriem Heike
Published: April 2006

▪ Abstract  The development of microstructured optical fibers has led to the realization of many optical properties in fiber form that were not previously attainable. This chapter reviews the background to this work and overviews both the fundamentals of and progress in fabricating and modeling these structures. Until relatively recently, most of the work in this field was based on silica glass; this chapter provides an update on progress in developing microstructured fibers from other materials such as soft glasses. Some of the key applications of microstructured fibers, including nonlinear fiber–based devices and fibers for high power light delivery, are also reviewed.
PATHOMECHANISMS IN CHANNELOPATHIES OF SKELETAL MUSCLE AND BRAIN
Authors: Cannon Stephen C.
Published: April 2006

Ion channelopathies are a diverse array of human disorders caused by mutations in ion channel genes. This review focuses on the pathogenic mechanisms of channelopathies affecting skeletal muscle and brain arising from mutations of voltage-gated ion channels and fast ligand-gated ion channels expressed at the surface membrane. Derangements in channel function alter the electrical excitability of the cell and thereby increase susceptibility to transient symptomatic attacks including myasthenia, periodic paralysis, myotonic stiffness, seizures, headache, dyskinesia, or episodic ataxia. Although these disorders are rare, they stand out as exemplary cases for which disease pathogenesis can be traced from a point mutation to altered protein function, to altered cellular activity, and to clinical phenotype. The study of these disorders has provided insights on channel structure-function relations, the physiological roles of ion channels, and rational approaches toward therapeutic intervention for many disorders of cellular excitability.
ENDOCANNABINOID-MEDIATED SYNAPTIC PLASTICITY IN THE CNS
Authors: Chevaleyre Vivien , Takahashi Kanji A. , Castillo Pablo E.
Published: April 2006

Changes in synaptic efficacy are thought to be crucial to experience-dependent modifications of neural function. The diversity of mechanisms underlying these changes is far greater than previously expected. In the last five years, a new class of use-dependent synaptic plasticity that requires retrograde signaling by endocannabinoids (eCB) and presynaptic CB1 receptor activation has been identified in several brain structures. eCB-mediated plasticity encompasses many forms of transient and long-lasting synaptic depression and is found at both excitatory and inhibitory synapses. In addition, eCBs can modify the inducibility of non-eCB-mediated forms of plasticity. Thus, the eCB system is emerging as a major player in synaptic plasticity. Given the wide distribution of CB1 receptors in the CNS, the list of brain structures and synapses expressing eCB-mediated plasticity is likely to expand.
NONCODING RNAS IN THE MAMMALIAN CENTRAL NERVOUS SYSTEM
Authors: Cao Xinwei , Yeo Gene , Muotri Alysson R. , Kuwabara Tomoko , Gage Fred H.
Published: April 2006

The central nervous system (CNS) is arguably one of the most complex systems in the universe. To understand the CNS, scientists have investigated a variety of molecules, including proteins, lipids, and various small molecules. However, one large class of molecules, noncoding RNAs (ncRNAs), has been relatively unexplored. ncRNAs function directly as structural, catalytic, or regulatory molecules rather than serving as templates for protein synthesis. The increasing variety of ncRNAs being identified in the CNS suggests a strong connection between the biogenesis, dynamics of action, and combinatorial regulatory potential of ncRNAs and the complexity of the CNS. In this review, we give an overview of the diversity and abundance of ncRNAs before delving into specific examples that illustrate their importance in the CNS. In particular, we cover recent evidence for the roles of microRNAs, small nucleolar RNAs, retrotransposons, the NRSE small modulatory RNA, and BC1/BC200 in the CNS. Finally, we speculate why ncRNAs are well adapted to improving organism-environment interactions.
THE ORGANIZATION OF BEHAVIORAL REPERTOIRE IN MOTOR CORTEX
Authors: Graziano Michael
Published: April 2006

Motor cortex in the primate brain was once thought to contain a simple map of the body's muscles. Recent evidence suggests, however, that it operates at a radically more complex level, coordinating behaviorally useful actions. Specific subregions of motor cortex may emphasize different ethologically relevant categories of behavior, such as interactions between the hand and the mouth, reaching motions, or defensive maneuvers to protect the body surface from impending impact. Single neurons in motor cortex may contribute to these behaviors by means of their broad tuning to idiosyncratic, multijoint actions. The mapping from cortex to muscles is not fixed, as was once thought, but instead is fluid, changing continuously on the basis of feedback in a manner that could support the control of higher-order movement parameters. These findings suggest that the motor cortex participates directly in organizing and controlling the animal's behavioral repertoire.
EARLY EVENTS IN OLFACTORY PROCESSING
Authors: Wilson Rachel I. , Mainen Zachary F.
Published: April 2006

Olfactory space has a higher dimensionality than does any other class of sensory stimuli, and the olfactory system receives input from an unusually large number of unique information channels. This suggests that aspects of olfactory processing may differ fundamentally from processing in other sensory modalities. This review summarizes current understanding of early events in olfactory processing. We focus on how odors are encoded by the activity of primary olfactory receptor neurons, how odor codes may be transformed in the olfactory bulb, and what relevance these codes may have for downstream neurons in higher brain centers. Recent findings in synaptic physiology, neural coding, and psychophysics are discussed, with reference to both vertebrate and insect model systems.
TRP ION CHANNELS AND TEMPERATURE SENSATION
Authors: Dhaka Ajay , Viswanath Veena , Patapoutian Ardem
Published: April 2006

The abilities to sense environmental and internal temperatures are required for survival, both for maintenance of homeostasis and for avoidance of tissue-damaging noxious temperatures. Vertebrates can sense external physical stimuli via specialized classes of neurons in the peripheral nervous system that project to the skin. Temperature-sensitive neurons can be divided into two classes: innocuous thermosensors (warm or cool) and noxious thermonociceptors (hot or cold). ThermoTRPs, a subset of the transient receptor potential family of ion channels, which are expressed in sensory nerve endings and in skin, respond to distinct thermal thresholds. In this review, we examine the extent to which thermoTRPs are responsible for providing a molecular basis for thermal sensation.
NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory
Authors: Hyman Steven E. , Malenka Robert C. , Nestler Eric J.
Published: April 2006

Addiction is a state of compulsive drug use; despite treatment and other attempts to control drug taking, addiction tends to persist. Clinical and laboratory observations have converged on the hypothesis that addiction represents the pathological usurpation of neural processes that normally serve reward-related learning. The major substrates of persistent compulsive drug use are hypothesized to be molecular and cellular mechanisms that underlie long-term associative memories in several forebrain circuits (involving the ventral and dorsal striatum and prefrontal cortex) that receive input from midbrain dopamine neurons. Here we review progress in identifying candidate mechanisms of addiction.
Dietary Proteins as Environmental Modifiers of Type 1 Diabetes Mellitus
Authors: Lefebvre David E. , Powell Karen L. , Strom Alexander , Scott Fraser W.
Published: April 2006

▪ Abstract  Type 1 diabetes is an autoimmune disease in which the patient's immune system destroys the insulin-secreting β-cells in the pancreatic islets of Langerhans. A majority of cases is thought to occur as a result of gene-environment interactions. The identity of the environmental factors remains unknown mainly because of the difficulty in linking past exposures with later disease development. Overall, the data suggest a model in which individuals develop diabetes by several different pathways, each influenced by numerous genetic and environmental variables. The most investigated environmental factors are diet and viruses. In this review, we examine the evidence that the source of dietary proteins can modify diabetes outcome, describe new approaches to identify candidate diabetes-related dietary agents, examine possible links with gut dysfunction, discuss some of the limitations, and propose a multifactorial model for dietary modification of diabetes. The key to diabetes pathogenesis, its prevention, and the ultimate success of β-cell replacement therapies lies in understanding how the environment controls disease expression. Dietary proteins could be one of these keys.
Glucagon-Like Peptide-2
Authors: Estall Jennifer L. , Drucker Daniel J.
Published: April 2006

▪ Abstract  Multiple peptide hormones produced within the gastrointestinal system aid in the regulation of energy homeostasis and metabolism. Among these is the intestinotrophic peptide glucagon-like peptide-2 (GLP-2), which is released following food intake and plays a significant role in the adaptive regulation of bowel mass and mucosal integrity. The discovery of GLP-2's potent growth-promoting and cytoprotective effects in the gastrointestinal (GI) tract stimulated interest in its use as a therapeutic agent for the treatment of GI diseases involving malabsorption, inflammation, and/or mucosal damage. Current research has focused on determining the physiological mechanisms contributing to the effects of GLP-2 and factors regulating its biological mechanisms of action. This chapter provides an overview of the biology of GLP-2 with a focus on the most recent findings on the role of this peptide hormone in the normal and diseased GI tract.
Regulation of Iron Metabolism by Hepcidin
Authors: Nemeth Elizabeta , Ganz Tomas
Published: April 2006

▪ Abstract  Hepcidin, a peptide hormone made in the liver, is the principal regulator of systemic iron homeostasis. Hepcidin controls plasma iron concentration and tissue distribution of iron by inhibiting intestinal iron absorption, iron recycling by macrophages, and iron mobilization from hepatic stores. Hepcidin acts by inhibiting cellular iron efflux through binding to and inducing the degradation of ferroportin, the sole known cellular iron exporter. Synthesis of hepcidin is homeostatically increased by iron loading and decreased by anemia and hypoxia. Hepcidin is also elevated during infections and inflammation, causing a decrease in serum iron levels and contributing to the development of anemia of inflammation, probably as a host defense mechanism to limit the availability of iron to invading microorganisms. At the opposite side of the spectrum, hepcidin deficiency appears to be the ultimate cause of most forms of hemochromatosis, either due to mutations in the hepcidin gene itself or due to mutations in the regulators of hepcidin synthesis. The emergence of hepcidin as the pathogenic factor in most systemic iron disorders should provide important opportunities for improving their diagnosis and treatment.
Risks and Benefits of Nutritional Support During Critical Illness
Authors: Debaveye Yves , Van den Berghe Greet
Published: April 2006

▪ Abstract  Critically ill patients who depend on intensive care for more than a few days reveal profound erosion of lean body mass, which is thought to contribute to high morbidity and mortality. Despite a shortfall of evidence that supplemental feeding actually alters clinical outcome of these life-threatening disease states, this observation evoked an almost universal, albeit often inappropriate, use of nutritional support (NS) in the critically ill, administered via the parenteral or the enteral route. Lack of knowledge and overenthusiasm subsequently resulted in complications associated with both parenteral nutrition (PN) and enteral nutrition (EN), which led to the standing controversy over which should be preferred. With time, however, it became clear that EN and PN are not mutually exclusive and that critically ill patients requiring NS should be fed according to the functional status of the gastrointestinal tract. In addition, tight blood glucose control with insulin is advised in fed critically ill patients because overall metabolic control appears to surpass any outcome benefit attributed to the route of feeding. Recently, various special nutritional formulas have been suggested to prevent or treat multiorgan failure in the critically ill, among other pathways via modulation of immune function. Although special nutritional formulas may be promising in a variety of clinical settings, based on currently available data, these cannot be recommended for routine use in critically ill patients.
Salt Handling and Hypertension
Authors: O'Shaughnessy Kevin M. , Karet Fiona E.
Published: April 2006

▪ Abstract  The kidney plays a central role in our ability to maintain an appropriate sodium balance, which is critical for the determination of blood pressure. The kidney's capacity for salt conservation may not be widely appreciated, and in general we consume vastly more salt than we need. Here we consider the socioeconomics of salt consumption, outline current knowledge of renal salt handling at the molecular level, describe some of the disease entities associated with abnormal sodium handling, give an overview of some of the animal models and their relevance to human disease, and examine the evidence that lowering our salt intake can help combat hypertension and cardiovascular disease.
A Model Plant Pathogen from the Kingdom Animalia:Heterodera glycines, the Soybean Cyst Nematode
Authors: Niblack T. L. , Lambert K. N. , Tylka G. L.
Published: April 2006

Abstract  The soybean cyst nematode, Heterodera glycines, adversely affects the production of soybean, Glycine max, in many areas of the world, particularly in the United States, where it is the most economically important soybean pathogen. Despite the availability of hundreds of H. glycines–resistant soybean cultivars, the nematode continues to be a major limiting factor in soybean production. The use of nonhost rotation and resistance are the primary means of reducing losses caused by the nematode, but each of these options has disadvantages. As a subject for study of nematode parasitism and virulence, H. glycines provides a useful model despite its obligately parasitic nature. Its obligately sexual reproduction and ready adaptation to resistant cultivars, formerly referred to as “race shift,” presents an excellent opportunity for the study of virulence in nematodes. Recent advances in H. glycines genomics have helped identify putative nematode parasitism genes, which, in turn, will aid in the understanding of nematode pathogenicity and virulence and may provide new targets for engineering nematode resistance.
Phenazine Compounds in Fluorescent Pseudomonas Spp. Biosynthesis and Regulation
Authors: Mavrodi Dmitri V. , Blankenfeldt Wulf , Thomashow Linda S.
Published: April 2006

Abstract  The phenazines include upward of 50 pigmented, heterocyclic nitrogen-containing secondary metabolites synthesized by some strains of fluorescent Pseudomonas spp. and a few other bacterial genera. The antibiotic properties of these compounds have been known for over 150 years, but advances within the past two decades have provided significant new insights into the genetics, biochemistry, and regulation of phenazine synthesis, as well as the mode of action and functional roles of these compounds in the environment. This new knowledge reveals conservation of biosynthetic enzymes across genera but raises questions about conserved biosynthetic mechanisms, and sets the stage for improving the performance of phenazine producers used as biological control agents for soilborne plant pathogens.
The Dawn of Fungal Pathogen Genomics
Authors: Xu Jin-Rong , Peng You-Liang , Dickman Martin B. , Sharon Amir
Published: April 2006

Abstract  Recent advances in sequencing technologies have led to a remarkable increase in the number of sequenced fungal genomes. Several important plant pathogenic fungi are among those that have been sequenced or are being sequenced. Additional fungal pathogens are likely to be sequenced in the near future. Analysis of the available genomes has provided useful information about genes that may be important for plant infection and colonization. Genome features, such as repetitive sequences, telomeres, conserved syntenic blocks, and expansion of pathogenicity-related genes, are discussed in detail with Magnaporthe oryzae (M. grisea) and Fusarium graminearum as examples. Functional and comparative genomic studies in plant pathogenic fungi, although still in the early stages and limited to a few pathogens, have enormous potential to improve our understanding of the molecular mechanisms involved in host-pathogen interactions. Development of advanced genomics tools and infrastructure is critical for efficient utilization of the vast wealth of available genome sequence information and will form a solid foundation for systems biology studies of plant pathogenic fungi.
RETHINKING THE RESOURCE CURSE: Ownership Structure, Institutional Capacity, and Domestic Constraints
Authors: Luong Pauline Jones , Weinthal Erika
Published: April 2006

▪ Abstract  Most political scientists and economists unequivocally accept the proposition that abundant mineral resources are more often a curse than a blessing, particularly for developing countries. We argue that the widely accepted contention that an abundance of mineral resources and the influx of external rents generated from these resources during boom periods are to blame for the so-called “resource curse” should be revisited. Instead, we offer a new research agenda for studying the problem of resource-rich states that shifts the locus of study away from the “paradox of plenty” to a more appropriate paradox—that the concentration of wealth impoverishes the state whereas the dispersion of wealth enriches the state. This agenda focuses on three interrelated issues: the structure of ownership over mineral resources, the importance of strong institutions, and the relative influence of domestic versus international factors.
MADISON IN BAGHDAD?: Decentralization and Federalism in Comparative Politics
Authors: Wibbels Erik
Published: April 2006

▪ Abstract  Research on comparative decentralization and federalism is a booming industry. Recent research integrates insights from political science, economics, and economic history in emphasizing the importance of incentives for the operation of decentralized government. Such work has focused particular attention on fiscal, representative, and party institutions. In reviewing the past decade's research, I make two arguments. First, the comparative research on decentralization and federalism provides a model for how comparative politics can address some of the most profound questions in social thought by focusing on a theoretically and empirically tractable aspect of governance. Second, although the research addresses many of the key questions in comparative politics, it also struggles with some of the same problems and challenges as comparative politics writ large, particularly the issue of institutional endogeneity. Attention to endogeneity is central to better understanding the workings of decentralized governments and providing less facile policy recommendations for the reform of places as diverse as the United States and Iraq.
RESPONDING TO SURPRISE
Authors: Wirtz James J.
Published: April 2006

▪ Abstract  This essay explores governmental and scholarly responses to the December 7, 1941 attack on Pearl Harbor and the September 11, 2001 attacks on the United States. Both events caught intelligence analysts, military officers, and elected officials by surprise. This essay describes the differences between the two events, especially in the ways official inquiries have helped shape our understanding of why the surprise occurred. Before both events, data suggesting that attacks were possible or even probable were available within the “intelligence pipeline.” The essay focuses on how scholars and official investigations reported and explained that finding. It also identifies continuities between the investigations that followed the Japanese and al Qaeda attacks on the United States.
A Closer Look at Oil, Diamonds, and Civil War
Authors: Ross Michael
Published: April 2006

▪ Abstract  Studies of natural resource wealth and civil war have been hampered by measurement error, endogeneity, lack of robustness, and uncertainty about causal mechanisms. This paper develops new measures and new tests to address these problems. It has four main findings. First, the likelihood of civil war in countries that produce oil, gas, and diamonds rose sharply from the early 1970s to the late 1990s; so did the number of rebel groups that sold contraband to raise money. Second, exogenous measures of oil, gas, and diamond wealth are robustly correlated with the onset of civil war. Still, these correlations are based on a small number of cases, and the substantive effects of resource wealth are sensitive to certain assumptions. Third, petroleum and diamond production lead to civil wars through at least three different mechanisms. Finally, the only resource variable robustly linked to conflict duration is a measure of “contraband,” which includes gemstones, timber, and narcotics.
Sons, Daughters, and Family Processes: Does Gender of Children Matter?
Authors: Raley Sara , Bianchi Suzanne
Published: April 2006

In the United States, parents prefer a child of each gender, and on many dimensions parents tend to treat sons and daughters similarly. However, fathers' investments appear to be somewhat higher in families with sons. Fathers spend more time with sons than with daughters. Fathers more often marry and stay married and mothers report more marital happiness in families with sons—although associations are weakening and differentials are not large. Divorced fathers more often have custody of sons than of daughters. Daughters do more housework than sons, mirroring the gendered division of labor in adulthood. Parental support of educational activities varies, with some parental behaviors greater for sons but others higher for daughters. Whether parents encourage gender differences or whether children's gender-differentiated behaviors elicit differential parental treatment cannot be easily determined with studies to date, most of which are cross-sectional or limited in other ways that hamper conclusions about causal mechanisms.
New Approaches to Understanding Racial Prejudice and Discrimination
Authors: Quillian Lincoln
Published: April 2006

This chapter reviews and critiques recent work on prejudice, discrimination, and racism, with an emphasis on evidence of continuing discrimination in the United States and efforts to understand its basis in prejudice. Three lines of research are the primary subject of the review: recent work on the measurement of discrimination, especially audit methods; theories of new prejudice and new racism following the Civil Rights movement; and research on implicit prejudicial attitudes. The most sophisticated new work on prejudice and discrimination is characterized by a multidimensional understanding of prejudice and/or the use of experimental methods. This review argues that research on implicit prejudice, largely developed by psychologists, provides an important new understanding of the basis of discrimination and should be incorporated in sociological accounts.
The Social Bases of Political Divisions in Post-Communist Eastern Europe
Authors: Evans Geoffrey
Published: April 2006

To what extent are the social bases of political divisions in former communist societies consistent with those observed in Western democracies? This review critically examines theoretical and empirical work on social cleavages in East European, post-communist societies. It considers the initial wave of hypotheses concerning the structuring of party support in the region and examines empirical evidence on the patterning of the social bases of political preferences that have accrued subsequently, as well as the somewhat sparser attempts at explaining the processes through which these patterns emerge and change. It points to the omissions and weaknesses of the analyses so far conducted and concludes that the post-communist era has seen the emergence of social bases to politics that are like those in the West and that help shape variations in patterns of party competition in these societies.
Video Cultures: Television Sociology in the “New TV” Age
Authors: Grindstaff Laura , Turow Joseph
Published: April 2006

We argue that the most significant and influential research on television over the past five decades positions the medium as a key site for addressing the complex interrelationship between culture and institutional/organizational power. Granting that such work is theoretically and methodologically diverse, we employ an organizational frame that groups political-economic approaches on the one hand and cultural approaches on the other. Political-economic approaches largely attend to issues of power at a macro level, focusing on how ownership and control of television along with the organization of television production practices shape and influence content; cultural approaches focus more on the expressive and symbolic dimensions of television programming and reception. At the same time, contemporary changes in the medium threaten to make past research on television appear quaint and anachronistic. The industry's transformation of television into continually emerging sets of multifaceted digital-interactive technologies challenges researchers to draw enduring perspectives from the older work and assess how they apply to the new-media environment. Consequently, we suggest the term “video cultures” in lieu of “television sociology” as a way of capturing future trends.
Lipid Metabolism and Liver Inflammation. II. Fatty liver disease and fatty acid oxidation
Authors: Reddy Janardan K. , Sambasiva Rao M.
Published: April 2006

Fatty liver disease (FLD), whether it is alcoholic FLD (AFLD) or nonalcoholic FLD (NAFLD), encompasses a morphological spectrum consisting of hepatic steatosis (fatty liver) and steatohepatitis. FLD has the inherent propensity to progress toward the development of cirrhosis and hepatocellular carcinoma. It is generally difficult to distinguish AFLD from NAFLD on morphological grounds alone despite the distinctions implied by these etiological designations. The indistinguishable spectrum of histological features of both AFLD and NAFLD suggests a possible convergence of pathogenetic mechanisms at some critical juncture that enables the progression of steatohepatitis toward cirrhosis and liver cancer. From a pathogenetic perspective, FLD may be considered a single disease with multiple etiologies. Excess energy consumption and reduced energy combustion appear to be critical events that culminate in lipid storage in the liver. Energy combustion in the liver is controlled by peroxisome proliferator-activated receptor (PPAR)-α-regulated mitochondrial and peroxisomal fatty acid β-oxidation systems and the microsomal ω-oxidation system. PPAR-α, a receptor for peroxisome proliferators, functions as a sensor for fatty acids (lipid sensor), and ineffective PPAR-α sensing can lead to reduced energy burning resulting in hepatic steatosis and steatohepatitis. Delineation of the pathogenetic aspects of FLD is necessary for developing novel therapeutic strategies for this disease.
Oxygen reperfusion is limited in the postischemic hypertrophic myocardium
Authors: Chung Youngran
Published: April 2006

Studies have shown that hypertrophied hearts are unusually vulnerable to ischemia. Compromised O2supply has been postulated as a possible explanation for this phenomenon on the basis of elongated O2diffusion distance and altered coronary vasculature found in hypertrophied myocardium. To examine the postulate, perfused heart experiments followed the metabolic and functional responses of hypertrophic myocardium to ischemia.1H/31P NMR was used to measure cellular oxygenation and energy level during ischemia-reperfusion. The left ventricles from spontaneously hypertensive rats (SHR) were enlarged by 48%. With this moderate degree of hypertrophy, cellular O2and energy levels were normal during baseline perfusion. After an ischemic episode, however, cellular O2was severely deprived in the SHR hearts compared with the normal hearts. Depressed postischemic O2reperfusion correlated well with depressed energetic and functional recovery. The results from the current study thus demonstrate a critical relationship between reperfused O2level and functional recovery in hypertrophic myocardium. The role of reperfused O2, however, is time dependent. During early reperfusion, factor(s) other than O2appear to limit functional recovery. It is when the mechanical function of the heart approaches a new steady state that O2becomes a dominant factor. Meanwhile, the finding of a normal O2level in preischemic SHR hearts defies the notion of preexisting hypoxia as a primer of ischemic damage.
Adventitial delivery of dominant-negative p67phoxattenuates neointimal hyperplasia of the rat carotid artery
Authors: Weaver Mitchell , Liu Jianhua , Pimentel David , Reddy Daniel J. , Harding Pamela , Peterson Edward L. , Pagano Patrick J.
Published: April 2006

Several essential components of NADPH oxidase, including p22phox, gp91phox(nox2) and its homologs nox1 and nox4, p47phox, p67phox, and rac1, are present in the vasculature. We previously reported that p67phoxis essential for adventitial fibroblast NADPH oxidase O2−production. Thus we postulated that inhibition of adventitial p67phoxactivity would attenuate angioplasty-induced hyperplasia. To test this hypothesis, we treated the adventitia of carotid arteries with a control adenovirus (Ad-control), a virus expressing dominant-negative p67phox(Ad-p67dn), or a virus expressing a competitive peptide (gp91ds) targeting the p47phox-gp91phoxinteraction (Ad-gp91ds). Common carotid arteries (CCAs) from male Sprague-Dawley rats were transfected with Ad-control, Ad-p67dn, or Ad-gp91ds in pluronic gel. After 2 days, a 2-F (Fogarty) catheter was used to injure CCAs in vivo. After 14 days, CCAs were perfusion-fixed and analyzed. In 13 experiments, digital morphometry suggested a reduction of neointimal hyperplasia with Ad-p67dn compared with Ad-control; however, the reduction did not reach statistical significance ( P = 0.058). In contrast, a significant reduction was achieved with Ad-gp91ds ( P = 0.006). No changes in medial area or remodeling were observed with either treatment. Moreover, adventitial fibroblast proliferation in vitro was inhibited by Ad-gp91ds but not by Ad-p67dn, despite confirmation that Ad-p67dn inhibits NADPH oxidase in fibroblasts. These data appear to suggest that a multicomponent vascular NADPH oxidase plays a role in neointimal hyperplasia. However, inhibition of p47phoxmay be more effective than inhibition of p67phoxat attenuating neointimal growth.
Premature senescence of endothelial cells: Methusaleh's dilemma
Authors: Chen Jun , Goligorsky Michael S.
Published: April 2006

Senescence has been considered a programmed cellular response, parallel to apoptosis, that is turned on when a cell reaches Hayflick's limit. Once cells enter the senescence program, they cease to proliferate and undergo a series of morphological and functional changes. Studies support a central role for Rb protein in controlling this process after it receives senescent signals from the p53 and p16 pathways. Cellular senescence is considered an essential contributor to the aging process and has been shown to be an important tumor suppression mechanism. In addition, emerging evidence suggests that senescence may also be involved in the pathogenesis of stem cell dysfunction and chronic human diseases. Under these circumstances cells undergo stress-induced premature senecence, which has several specific features. Focusing on endothelial cells, we discuss recent advances in our understanding of the stresses and their pathways that prompt the premature senescence response, evaluate their correlation with the apoptotic response, and examine their links to the development of chronic diseases and the impaired function of endothelial progenitor cells, with the emphasis on vasculopathy. Emerging novel therapeutic interventions based on recent experimental findings are also reviewed.
JNK activation decreases PP2A regulatory subunit B56α expression and mRNA stability and increases AUF1 expression in cardiomyocytes
Authors: Glaser Nicole D. , Lukyanenko Yevgeniya O. , Wang Yibin , Wilson Gerald M. , Rogers Terry B.
Published: April 2006

A central feature of heart disease is a molecular remodeling of signaling pathways in cardiac myocytes. This study focused on novel molecular elements of MAPK-mediated alterations in the pattern of gene expression of the protein phosphatase 2A (PP2A). In an established model of sustained JNK activation, a 70% decrease in expression of the targeting subunit of PP2A, B56α, was observed in either neonatal or adult cardiomyocytes. This loss in protein abundance was accompanied by a decrease of 69% in B56α mRNA steady-state levels. Given that the 3′-untranslated region of this transcript contains adenylate-uridylate-rich elements known to regulate mRNA degradation, experiments explored the notion that instability of B56α mRNA accounts for the response. mRNA time-course analyses with real-time PCR methods showed that B56α transcript was transformed from a stable (no significant decay over 1 h) to a labile form that rapidly degraded within minutes. These results were supported by complementary experiments that revealed that the RNA-binding protein AUF1, known to destabilize target mRNA, was increased fourfold in JNK-activated cells. A variety of other stress-related stimuli, such as p38 MAPK activation and phorbol ester, upregulated AUF1 expression in cultured cardiac cells as well. In addition, gel mobility shift assays demonstrated that p37AUF1 binds with nanomolar affinity to segments of the B56α 3′-untranslated region. Thus these studies provide new evidence that signaling-induced mRNA instability is an important mechanism that underlies the changes in the pattern of gene expression evoked by stress-activated pathways in cardiac cells.
Relationship of pulmonary vein flow to left ventricular short-axis epicardial displacement in diastole: model-based prediction with in vivo validation
Authors: Riordan Matt M. , Kovács Sándor J.
Published: April 2006

Previous studies in healthy humans have established that the (≈850 ml) volume enclosed by the pericardial sac is nearly constant over the cardiac cycle, exhibiting a transient ≈5% decrease (≈40 ml) from end diastole to end systole. This volume decrease manifests as a “crescent” at the ventricular free wall level when short-axis MRI images of the epicardial surface acquired at end systole and end diastole are superimposed. On the basis of the (near) constant-volume property of the four-chambered heart, the volume decrease (“crescent effect”) must be restored during subsequent early diastolic filling via the left atrial conduit volume. Therefore, volume conservation-based modeling predicts that pulmonary venous (PV) Doppler D-wave volume must be causally related to the radial displacement of the epicardium (Δ) (i.e., magnitude of “crescent effect” in the radial direction). We measured Δ from M-mode echocardiographic images and measured D-wave velocity-time integral (VTI) from Doppler PV flow of the right superior PV in 11 subjects with catheterization-determined normal physiology. In accordance with model prediction, high correlation was observed between Δ and D-wave VTI ( r = 0.86) and early D-wave VTI measured to peak D-wave velocity ( r = 0.84). Furthermore, selected subjects with various pathological conditions had values of Δ that differed significantly. These observations demonstrate the volume conservation-based causal relationship between radial pericardial displacement of the left ventricle and the PV D-wave-generated filling volume in healthy subjects as well as the potential role of the M-mode echo-derived radial epicardial displacement index Δ as a regional (radial) parameter of diastolic function.