bluuebunny/crossref_metadata_2025 huggingface dataset:
N-Linked Glycosylation Attenuates H3N2 Influenza Viruses
Authors: Vigerust David J. , Ulett Kimberly B. , Boyd Kelli L. , Madsen Jens , Hawgood Samuel , McCullers Jonathan A.
Published: June 2007

Over the last four decades, H3N2 subtype influenza A viruses have gradually acquired additional potential sites for glycosylation within the globular head of the hemagglutinin (HA) protein. Here, we have examined the biological effect of additional glycosylation on the virulence of H3N2 influenza viruses. We created otherwise isogenic reassortant viruses by site-directed mutagenesis that contain additional potential sites for glycosylation and examined the effect on virulence in naïve BALB/c, C57BL/6, and surfactant protein D (SP-D)-deficient mice. The introduction of additional sites was consistent with the sequence of acquisition in the globular head over the past 40 years, beginning with two sites in 1968 to the seven sites found in contemporary influenza viruses circulating in 2000. Decreased morbidity and mortality, as well as lower viral lung titers, were seen in mice as the level of potential glycosylation of the viruses increased. This correlated with decreased evidence of virus-mediated lung damage and increased in vitro inhibition of hemagglutination by SP-D. SP-D-deficient animals displayed an inverse pattern of disease, such that more highly glycosylated viruses elicited disease equivalent to or exceeding that of the wild type. We conclude from these data that increased glycosylation of influenza viruses results in decreased virulence, which is at least partly mediated by SP-D-induced clearance from the lung. The continued exploration of interactions between highly glycosylated viruses and surfactant proteins may lead to an improved understanding of the biology within the lung and strategies for viral control.
Estrogen receptor-α predominantly mediates the salutary effects of 17β-estradiol on splenic macrophages following trauma-hemorrhage
Authors: Suzuki Takao , Shimizu Tomoharu , Yu Huang-Ping , Hsieh Ya-Ching , Choudhry Mashkoor A. , Bland Kirby I. , Chaudry Irshad H.
Published: June 2007

Although 17β-estradiol administration following trauma-hemorrhage prevents the suppression in splenic macrophage cytokine production, it remains unknown whether the salutary effects are mediated via estrogen receptor (ER)-α or ER-β and which signaling pathways are involved in such 17β-estradiol effects. Utilizing ER-α- or ER-β-specific agonists, this study examined the role of ER-α and ER-β in 17β-estradiol-mediated restoration of macrophage cytokine production following trauma-hemorrhage. In addition, since MAPK and NF-κB are known to regulate macrophage cytokine production, we also examined the activation of those signaling molecules. Male rats underwent trauma-hemorrhage (mean arterial pressure of 40 mmHg for 90 min) and fluid resuscitation. The ER-α agonist propyl pyrazole triol (PPT; 5 μg/kg), the ER-β agonist diarylpropionitrile (DPN; 5 μg/kg), 17β-estradiol (50 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. Twenty-four hours thereafter, splenic macrophages were isolated, and their IL-6 and TNF-α production and activation of MAPK and NF-κB were measured. Macrophage IL-6 and TNF-α production and MAPK activation were decreased, whereas NF-κB activity was increased, following trauma-hemorrhage. PPT or 17β-estradiol administration after trauma-hemorrhage normalized those parameters. DPN administration, on the other hand, did not normalize the above parameters. Since PPT but not DPN administration following trauma-hemorrhage was as effective as 17β-estradiol in preventing the suppression in macrophage cytokine production, it appears that ER-α plays the predominant role in mediating the salutary effects of 17β-estradiol on macrophage cytokine production following trauma-hemorrhage and that such effects are likely mediated via normalization of MAPK but not NF-κB signaling pathways.
Xenogenic macrophage immunization reduces atherosclerosis in apolipoprotein E knockout mice
Authors: Yamashita Tomoya , Kawashima Seinosuke , Hirase Tetsuaki , Shinohara Masakazu , Takaya Tomofumi , Sasaki Naoto , Takeda Masafumi , Tawa Hideto , Inoue Nobutaka , Hirata Ken-ichi , Yokoyama Mitsuhiro
Published: June 2007

Atherosclerosis is a complex chronic inflammatory disease in which macrophages play a critical role, and the intervention of the inflammatory process in atherogenesis could be a therapeutic strategy. In this study, we investigated the efficacy of xenogenic macrophage immunization on the atherosclerotic lesion formation in a model of murine atherosclerosis. Apolipoprotein E knockout (apoE-KO) mice were repeatedly immunized with formaldehyde-fixed cultured human macrophages (phorbol ester-stimulated THP-1 cells), using human serum albumin as a control protein or HepG2 cells as human control cells, once a week for four consecutive weeks. The vehicle phosphate-buffered saline was injected in the nonimmunized controls. THP-1 immunization induced antibodies that are immunoreactive with mouse macrophages. Although the plasma lipid levels were unchanged by the immunization, the atherosclerotic lesion area in the aortic root was significantly reduced by >50% in 16-wk-old THP-1-immunized apoE-KO mice compared with that in control mice. THP-1 immunization reduced in vivo macrophage infiltration, reduced in vitro macrophage adhesion, and changed cytokine production by macrophages to the antiatherogenic phenotype. Xenogenic macrophage immunization protects against the development of atherosclerosis in apoE-KO mice by modulating macrophage function in which antibodies induced by the immunization are likely to be involved. This method is a novel and potentially useful cell-mediated immune therapeutic technique against atherosclerosis.
Role of endosomal Na+-K+-ATPase and cardiac steroids in the regulation of endocytosis
Authors: Feldmann Tomer , Glukmann Vladimir , Medvenev Eleonora , Shpolansky Uri , Galili Dana , Lichtstein David , Rosen Haim
Published: June 2007

Plasma membrane Na+-K+-ATPase, which drives potassium into and sodium out of the cell, has important roles in numerous physiological processes. Cardiac steroids (CS), such as ouabain and bufalin, specifically interact with the pump and affect ionic homeostasis, signal transduction, and endocytosed membrane traffic. CS-like compounds are present in mammalian tissues, synthesized in the adrenal gland, and considered to be new family of steroid hormones. In this study, the mechanism of Na+-K+-ATPase involvement in the regulation of endocytosis is explored. We show that the effects of various CS on changes in endosomal pH are mediated by the pump and correspond to their effects on endosomal membrane traffic. In addition, it was found that CS-induced changes in endocytosed membrane traffic were dependent on alterations in [Na+] and [H+] in the endosome. Furthermore, we show that various CS differentially regulate endosomal pH and membrane traffic. The results suggest that these differences are due to specific binding characteristics. Based on our observations, we propose that Na+-K+-ATPase is a key player in the regulation of endosomal pH and endocytosed membrane traffic. Furthermore, our results raise the possibility that CS-like hormones regulate differentially intracellular membrane traffic.
The effects of salt-induced hypertension on α1-adrenoreceptor expression and cardiovascular physiology in the rainbow trout (Oncorhynchus mykiss)
Authors: Chen Xi , Moon Thomas W. , Olson Kenneth R. , Dombkowski Ryan A. , Perry Steve F.
Published: June 2007

Experiments were conducted on rainbow trout to determine the impact of dietary salt on arterial blood pressure. After 4–6 wk, fish fed a salt-enriched diet exhibited a 37% elevation of dorsal aortic pressure (from 23.8 ± 1.2 to 32.6 ± 1.4 mmHg) and an 18% increase in ventral aortic pressure (from 33.0 ± 1.5 to 38.9 ± 1.3 mmHg). The hypertension presumably reflected the increase in cardiac output (from 31.0 ± 0.8 to 36.4 ± 2.2 ml·min−1·kg−1) because systemic and branchial resistances were statistically unaltered by salt feeding. The chronic hypertension was associated with a decrease in the pressor responses of the systemic vasculature to catecholamines and hypercapnia in the salt-fed fish. The reduction in α-adrenergic responsiveness of the systemic vasculature is consistent with desensitization or loss of functional α-adrenoceptors (α-ARs). In support of this idea, the salt-fed fish exhibited significantly decreased levels of α1D-AR mRNA in the dorsal aorta and the afferent (ABA) and efferent branchial arteries (EBA). In contrast, however, the results obtained from norepinephrine dose-response curves for EBA and ABA vascular rings in vitro did not provide evidence for loss of function of branchial artery α1-ARs in the salt-fed fish. Indeed, the EC50for the EBA norepinephrine dose-response curve was significantly reduced (from 3.75 × 10−7to 2.12 × 10−7M) in the salt-fed fish, indicating an increase in the binding affinity of the α1-ARs.
Postnatal maturation attenuates pressure-evoked myogenic tone and stretch-induced increases in Ca2+in rat cerebral arteries
Authors: Charles Shelton M. , Zhang Lubo , Longo Lawrence D. , Buchholz John N. , Pearce William J.
Published: June 2007

Although postnatal maturation potently modulates agonist-induced cerebrovascular contractility, its effects on the mechanisms mediating cerebrovascular myogenic tone remain poorly understood. Because the regulation of calcium influx and myofilament calcium sensitivity change markedly during early postnatal life, the present study tested the general hypothesis that early postnatal maturation increases the pressure sensitivity of cerebrovascular myogenic tone via age-dependent enhancement of pressure-induced calcium mobilization and myofilament calcium sensitivity. Pressure-induced myogenic tone and changes in artery wall intracellular calcium concentrations ([Ca2+]i) were measured simultaneously in endothelium-denuded, fura-2-loaded middle cerebral arteries (MCA) from pup [postnatal day 14 (P14)] and adult (6-mo-old) Sprague-Dawley rats. Increases in pressure from 20 to 80 mmHg enhanced myogenic tone in MCA from both pups and adults although the normalized magnitudes of these increases were significantly greater in pup than adult MCA. At each pressure step, vascular wall [Ca2+]iwas also significantly greater in pup than in adult MCA. Nifedipine significantly attenuated pressure-evoked constrictions in pup MCA and essentially eliminated all responses to pressure in the adult MCA. Both pup and adult MCA exhibited pressure-dependent increases in calcium sensitivity, as estimated by changes in the ratio of pressure-induced myogenic tone to wall [Ca2+]i. However, there were no differences in the magnitudes of these increases between pup and adult MCA. The results support the view that regardless of postnatal age, changes in both calcium influx and myofilament calcium sensitivity contribute to the regulation of cerebral artery myogenic tone. The greater cerebral myogenic response in P14 compared with adult MCA appears to be due to greater pressure-induced increases in [Ca2+]i, rather than enhanced augmentation of myofilament calcium sensitivity.
Frames of Reference for Gaze Saccades Evoked During Stimulation of Lateral Intraparietal Cortex
Authors: Constantin A. G. , Wang H. , Martinez-Trujillo J. C. , Crawford J. D.
Published: June 2007

Previous studies suggest that stimulation of lateral intraparietal cortex (LIP) evokes saccadic eye movements toward eye- or head-fixed goals, whereas most single-unit studies suggest that LIP uses an eye-fixed frame with eye-position modulations. The goal of our study was to determine the reference frame for gaze shifts evoked during LIP stimulation in head-unrestrained monkeys. Two macaques ( M1 and M2) were implanted with recording chambers over the right intraparietal sulcus and with search coils for recording three-dimensional eye and head movements. The LIP region was microstimulated using pulse trains of 300 Hz, 100–150 μA, and 200 ms. Eighty-five putative LIP sites in M1 and 194 putative sites in M2 were used in our quantitative analysis throughout this study. Average amplitude of the stimulation-evoked gaze shifts was 8.67° for M1 and 7.97° for M2 with very small head movements. When these gaze-shift trajectories were rotated into three coordinate frames (eye, head, and body), gaze endpoint distribution for all sites was most convergent to a common point when plotted in eye coordinates. Across all sites, the eye-centered model provided a significantly better fit compared with the head, body, or fixed-vector models (where the latter model signifies no modulation of the gaze trajectory as a function of initial gaze position). Moreover, the probability of evoking a gaze shift from any one particular position was modulated by the current gaze direction (independent of saccade direction). These results provide causal evidence that the motor commands from LIP encode gaze command in eye-fixed coordinates but are also subtly modulated by initial gaze position.
Action-Potential-Independent GABAergic Tone Mediated by Nicotinic Stimulation of Immature Striatal Miniature Synaptic Transmission
Authors: Liu Zhi , Otsu Yo , Vasuta Cristina , Nawa Hiroyuki , Murphy Timothy H.
Published: June 2007

Stimulation of presynaptic nicotinic acetylcholine receptors (nAChRs) increases the frequency of miniature excitatory synaptic activity (mEPSCs) to a point where they can promote cell firing in hippocampal CA3 neurons. We have evaluated whether nicotine regulation of miniature synaptic activity can be extended to inhibitory transmission onto striatal medium spiny projection neurons (MSNs) in acute brain slices. Bath application of micromolar nicotine typically induced 12-fold increases in the frequency of miniature inhibitory synaptic currents (mIPSCs). Little effect was observed on the amplitude of mIPSCs or mEPSCs under these conditions. Nicotine stimulation of mIPSCs was dependent on entry of extracellular calcium because removal of calcium from perfusate was able to block its action. To assess the potential physiological significance of the nicotine-stimulated increase in mIPSC frequency, we also examined the nicotine effect on evoked IPSCs (eIPSCs). eIPSCs were markedly attenuated by nicotine. This effect could be attributed to two potential mechanisms: transmitter depletion due to extremely high mIPSC rates and/or a reduction in presynaptic excitability associated with nicotinic depolarization. Treatment with low concentrations of K+ was able to in part mimic nicotine's stimulatory effect on mIPSCs and inhibitory effect on eIPSCs. Current-clamp recordings confirmed a direct depolarizing action of nicotine that could dampen eIPSC activity leading to a switch to striatal inhibitory synaptic transmission mediated by tonic mIPSCs.
On the Generalized Ulam-Gavruta-Rassias Stability of Mixed-Type Linear and Euler-Lagrange-Rassias Functional Equations
Authors: Nakmahachalasint Paisan
Published: June 2007

In this paper, the mixed-type linear and Euler-Lagrange-Rassias functional equations introduced by J. M. Rassias is generalized to the followingn-dimensional functional equation:f(∑i=1nxi)+(n−2)∑i=1nf(xi)=∑1≤i2. We prove the general solutions and investigate its generalized Ulam-Gavruta-Rassias stability.
Nonlinear Periodic Systems with thep-Laplacian: Existence and Multiplicity Results
Authors: Papalini Francesca
Published: June 2007

We study second-order nonlinear periodic systems driven by the vectorp-Laplacian with a nonsmooth, locally Lipschitz potential function. Under minimal and natural hypotheses on the potential and using variational methods based on the nonsmooth critical point theory, we prove existence theorems and a multiplicity result. We conclude the paper with an existence theorem for the scalar problem, in which the energy functional is indefinite (unbounded from both above and below).
T-Homotopy and Refinement of Observation—Part II: Adding NewT-Homotopy Equivalences
Authors: Gaucher Philippe
Published: June 2007

This paper is the second part of a series of papers about a new notion ofT-homotopy of flows. It is proved that the old definition ofT-homotopy equivalence does not allow the identification of the directed segment with the 3-dimensional cube. This contradicts a paradigm of dihomotopy theory. A new definition ofT-homotopy equivalence is proposed, following the intuition of refinement of observation. And it is proved that up to weakS-homotopy, an oldT-homotopy equivalence is a newT-homotopy equivalence. The left properness of the weakS-homotopy model category of flows is also established in this part. The latter fact is used several times in the next papers of this series.
The Best Achievableℋ2Tracking Performances for SIMO Feedback Control Systems
Authors: Hara Shinji , Bakhtiar Toni , Kanno Masaaki
Published: June 2007

This paper is concerned with the inherentℋ2tracking performance limitation of single-input and multiple-output (SIMO) linear time-invariant (LTI) feedback control systems. The performance is measured by the tracking error between a step reference input and the plant output with additional penalty on control input. We employ the plant augmentation strategy, which enables us to derive analytical closed-form expressions of the best achievable performance not only for discrete-time system, but also for continuous-time system by exploiting the delta domain version of the expressions.
Genes and Environment in Common Neonatal Lung Disease
Authors: Hallman Mikko , Marttila Riitta , Pertile Riccardo , Ojaniemi Marja , Haataja Ritva
Published: June 2007

Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) are common, serious lung diseases in preterm infants. Polymorphism of the genes involved in basic lung function and alveolar stability, lung differentiation and pulmonary host defense may influence the risk. Natural selection has refined the genes responsible for cardiopulmonary adaptation and resistance against pneumonia in term and near-term infants. Before the era of antibiotics, however, virtually all very preterm infants died of asphyxia, respiratory failure or infections. Today, the degree of prematurity plays a dominant role in susceptibility to serious lung disease. In addition, genetic polymorphism and constitution modulate the risk of RDS and BPD that have different, partly overlapping predisposition. According to twin studies, the genetic impact on the risk of RDS and BPD among preterm and very preterm infants is 35–65%. Individual disease genes generally have low penetrance. Large-scale genetic studies are required as part of neonatal and perinatal research in order to learn about the risk factors and to investigate pharmacogenetics. The aim in the future is to individualize therapies.
Hydrophobic Surfactant Proteins and Their Analogues
Authors: Walther Frans J. , Waring Alan J. , Sherman Mark A. , Zasadzinski Joseph A. , Gordon Larry M.
Published: June 2007

Lung surfactant is a complex mixture of phospholipids and four surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D). Its major function in the lung alveolus is to reduce surface tension at the air-water interface in the terminal airways by the formation of a surface-active film enriched in surfactant lipids, hence preventing cellular collapse during respiration. Surfactant therapy using bovine or porcine lung surfactant extracts, which contain only polar lipids and native SP-B and SP-C, has dramatically improved the therapeutic outcomes of preterm infants with respiratory distress syndrome (RDS). One important goal of surfactant researchers is to replace animal-derived therapies with fully synthetic preparations based on SP-B and SP-C, produced by recombinant technology or peptide synthesis, and reconstituted with selected synthetic lipids. Here, we review recent research developments with peptide analogues of SP-B and SP-C, designed using either the known primary sequence and three-dimensional (3D) structure of the native proteins or, alternatively, the known 3D structures of closely homologous proteins. Such SP-B and SP-C mimics offer the possibility of studying the mechanisms of action of the respective native proteins, and may allow the design of optimized surfactant formulations for specific pulmonary diseases (e.g., acute lung injury (ALI) or acute respiratory distress syndrome (ARDS)). These synthetic surfactant preparations may also be a cost-saving therapeutic approach, with better quality control than may be obtained with animal-based treatments.
The Glomerular Transcriptome and Proteome
Authors: Betsholtz Christer , He Liqun , Takemoto Minoru , Norlin Jenny , Sun Ying , Patrakka Jaakko , Tryggvason Karl
Published: June 2007

Histopathology provides the current basis for classification and diagnosis of glomerular disorders. Molecular profiling methods, such as microarray analysis of mRNA expression, have rapidly emerged over the past years and are now applicable to minute amounts of tissue material, such as glomeruli from embryos or adult experimental animals, or from human renal needle biopsies. This review summarizes current efforts aiming at the determination of the glomerular transcriptome and proteome during development, in the healthy adult, and in disease. These studies are encouraging and show that comprehensive molecular profiling of the kidney glomerulus will most likely provide significant new insights into the normal structure and function of the glomerular filter, the molecular mechanisms of glomerular development, the diagnosis and classification of glomerular disease, and the pathogenic mechanisms underlying the stepwise breakdown of glomerular filter function that accompanies several common systemic disorders.
Role of Transcription Factors in Podocytes
Authors: Rascle Anne , Suleiman Hani , Neumann Tanja , Witzgall Ralph
Published: June 2007

Despite a wealth of information on structural proteins, comparatively little is known on the transcriptional regulation of podocyte structure and function. In this review we will highlight those transcription factors which, by gene inactivation or classical transgenic experiments, have been shown to be essential for podocytes or probably will turn out to be so. The tumor suppressor protein WT1 is not only indispensable for the initial stages of kidney development, but also very likely maintains the integrity of the fully differentiated podocyte. In the kidney, the LIM homeodomain transcription factor LMX1B is specifically synthesized in podocytes, and mutations in LMX1B lead to nail-patella syndrome and the associated nephropathy. Other transcription factors such as hypoxia-inducible factors and PAX2 are likely to play a role in podocytes, whereas the significance of others, e.g. of POD1 and CITED2, is more speculative at this point.
Podocyte Damage Resulting in Podocyturia: A Potential Diagnostic Marker to Assess Glomerular Disease Activity
Authors: Petermann Arndt , Floege Jürgen
Published: June 2007

A decrease in podocyte number contributes to the development of glomerulosclerosis in most forms of glomerular disease [1,2,3,4,5]. Traditionally, it has been argued that this decrease may be caused by the inability of podocytes to proliferate and replace those lost following immune, metabolic, toxic or hemodynamic injury. These data contrast with recent studies showing that podocytes are able to enter the cell cycle after injury, to progress through the different phases of the cell cycle and even enter mitosis. However, experimental and human data suggest that entry of podocytes into the cell cycle may result in reduced adhesion to the glomerular basement membrane with subsequent loss of podocytes into the urine and excretion of both viable and apoptotic podocytes. Viable urinary podocytes can be cultivated ex vivo for up to 2–3 weeks and in experimental models precede the onset of proteinuria. More importantly, podocyturia can decrease despite persistent proteinuria. The latter observation suggests that podocyturia may serve as the first non-invasive marker of ‘active’ glomerular damage and might thus drive therapeutic interventions in the future. However, at present technical issues still prevent a broad clinical application of podocyturia detection in clinical practice.
Development of Fibre-Optic Confocal Microscopy for Detection and Diagnosis of Dental Caries
Authors: Rousseau C. , Poland S. , Girkin J.M. , Hall A.F. , Whitters C.J.
Published: June 2007

We report on the development of a fibre-optics-based confocal imaging system for the detection and potential diagnosis of early dental caries. A novel optical instrument, capable of recording axial profiles through caries lesions using single-mode optical fibres, has been developed. The practical study illustrates that miniature confocal devices based around single-mode optical fibres may provide additional diagnostic information for the general dental practitioner.
Development and Aging of the Vertebrate Visual System
Authors: Lorke Dietrich E.
Published: June 2007

This special issue encompasses articles dealing with a number of unique features of the vertebrate visual system. These characteristics make it an established model to study the molecular and genetic control of axonal growth, neurogenesis, gliogenesis and regeneration in the central nervous system. The clinical relevance of developmental malformations and age-related diseases is briefly described. The possible effects of visual inputs on melatonin secretion and changes in this system during aging are summarized.
Extrapineal Melatonin: General Conception, Localization and Biological Role in the Visual System
Authors: Kvetnoy Igor M. , Smirnova Irina O. , Polyakova Victoria O.
Published: June 2007

During the last decade, much attention has centered on melatonin, which was considered to be only a hormone of the pineal gland for many years. As soon as highly sensitive antibodies to indolealkylamines became available, melatonin was identified not only in the pineal gland, but also in extrapineal tissues and cells, e.g. the retina, Harderian gland, gut mucosa, cerebellum, airway epithelium, liver, kidney, adrenals, pancreas, thyroid gland and thymus. Also, melatonin has been found in some non-endocrine cells, e.g. mast cells, natural killer cells, eosinophilic leukocytes, platelets and endothelial and other cells. Functionally, melatonin-producing cells are part and parcel of the diffuse neuroendocrine system as a universal system of response, control and organism protection. The influence of aging upon melatonin-synthesizing cells in the gut is summarized. Melatonin synthesis in the visual system and its hormone level, similarly to the pineal gland, reflect the interaction between the circadian clock and the photic environment. Since retinal melatonin does not contribute to circulating levels and melatonin receptors are present in the retina, its effects on the visual system are primarily mediated by a paracrine mechanism. Although the physiological role of melatonin in the visual system is not exactly determined yet, it apparently includes regulation of gene expression, visual sensitivity and the protection of ocular structures from oxidative damage.
Notch Signaling in Blood Vessels
Authors: Hofmann Jennifer J. , Iruela-Arispe M. Luisa
Published: June 2007

It has become increasingly clear that the Notch signaling pathway plays a critical role in the development and homeostasis of the cardiovascular system. This notion has emerged from loss- and gain-of-function analysis and from the realization that several hereditary cardiovascular disorders originate from gene mutations that have a direct impact on Notch signaling. Current research efforts are focused on determining the specific cellular and molecular effects of Notch signaling. The rationale for this has stemmed from the clinical importance and therapeutic potential of modulating vascular formation during various disease states. A more complete appreciation of Notch signaling, as it relates to vascular morphogenesis, requires an in-depth knowledge of expression patterns of the various signaling components and a comprehensive understanding of downstream targets. The goal of this review is to summarize current knowledge regarding Notch signaling during vascular development and within the adult vascular wall. Our focus is on the genetic analysis and cellular experiments that have been performed with Notch ligands, receptors, and downstream targets. We also highlight questions and controversies regarding the contribution of this pathway to vascular development.
cAMP and cGMP Signaling Cross-Talk
Authors: Zaccolo Manuela , Movsesian Matthew A.
Published: June 2007

Cyclic nucleotide phosphodiesterases regulate cAMP-mediated signaling by controlling intracellular cAMP content. The cAMP-hydrolyzing activity of several families of cyclic nucleotide phosphodiesterases found in human heart is regulated by cGMP. In the case of PDE2, this regulation primarily involves the allosteric stimulation of cAMP hydrolysis by cGMP. For PDE3, cGMP acts as a competitive inhibitor of cAMP hydrolysis. Several cGMP-mediated responses in cardiac cells, including a potentiation of Ca2+currents and a diminution of the responsiveness to β-adrenergic receptor agonists, have been shown to result from the effects of cGMP on cAMP hydrolysis. These effects appear to be dependent on the specific spatial distribution of the cGMP-generating and cAMP-hydrolyzing proteins, as well as on the intracellular concentrations of the two cyclic nucleotides. Gaining a more precise understanding of how these cross-talk mechanisms are individually regulated and coordinated is an important direction for future research.
The Macrophage at the Crossroads of Insulin Resistance and Atherosclerosis
Authors: Liang Chien-Ping , Han Seongah , Senokuchi Takafumi , Tall Alan R.
Published: June 2007

The macrophage has emerged as an important player in the pathogenesis of both atherosclerosis and insulin resistance. Cross-talk between inflammatory macrophages and adipocytes may be involved in insulin resistance in peripheral tissues. Defective insulin signaling in cells of the arterial wall including macrophages may promote the development of atherosclerosis. Insulin resistant macrophages are more susceptible to endoplasmic reticulum stress and apoptosis in response to various stimuli such as nutrient deprivation, free cholesterol loading, and oxidized LDL. Increased apoptosis of insulin resistant macrophages and impaired phagocytic clearance of apoptotic cells by insulin resistant macrophages in atherosclerotic lesions may lead to enhanced postapoptotic necrosis, larger lipid-rich cores, increased inflammation, and more complex vulnerable plaques.
Shear-lag Analysis of the Effect of Thickness on Spring-in of Curved Composites
Authors: Wisnom Michael R. , Potter Kevin D. , Ersoy Nuri
Published: June 2007

A new analytical solution is presented for spring-in of curved thermoset matrix composites taking into account the low shear stiffness of the material in the rubbery state before it is fully cured. It is shown that shear-lag through the thickness can have a significant effect in reducing spring-in arising from thermal stresses and chemical shrinkage between gelation and vitrification. Results are presented in a nondimensional form that shows the influences of subtended angle, through-thickness shrinkage, the ratio of curved arc length to part thickness, and the ratio of in-plane modulus to rubbery interlaminar shear modulus, providing greater physical insight into the spring-in mechanism. The analysis predicts a significant effect of thickness on spring-in angle. This is verified by experimental measurements on cross-ply carbon-epoxy C-sections cured on a carbon fiber tool, confirming the validity of the new solution.
Against their will: Young women's nonagentic sexual experiences
Authors: Crown Laurel , Roberts Linda J.
Published: June 2007

This study introduces the notion of nonagentic sexual interaction and presents findings describing its prevalence, characteristics, and consequences among a representative sample of 566 undergraduate women. One third of respondents reported one or more nonagentic sexual interactions during a single academic year, and more than half of the senior respondents reported one or more interactions during their college careers. Relations between these interactions' behavioral characteristics and four psychological outcome measures provide limited empirical support for the notion that interactions involving a higher degree of physical intrusion and more forceful tactics are more distressing than those involving less intrusion and more subtle tactics. Narrative accounts illustrate the complexity of these interactions. Implications of nonagentic sexual experiences for healthy sexuality development are discussed.
Avoiding costly mating mistakes: Ovulatory shifts in personal mate value assessment
Authors: Beaulieu David A.
Published: June 2007

An accurate assessment of one's mate value aids one in avoiding mating mistakes. However, the utility of assessing one's mate value is not constant. As the costs of making undesirable mating decisions increase, attentional resources devoted towards mate value assessment should also increase. Thus, during peak fertility (when the costs of mating mistakes are presumably greater), women should allocate resources towards assessment of personal mate value. As predicted, compared with women with low conception risk, women at peak fertility reported greater attractiveness comparison frequencies and placed greater emphasis on attractiveness in defining self-image. Past sexual experience heightened activation of these processes. Additionally, mate value was more strongly associated with appraisal of one's attractiveness and mate selection standards during peak fertility.
Reassessing the role of partnered women in migration decision-making and migration outcomes
Authors: Hiller Harry H. , McCaig Kendall S.
Published: June 2007

Previous research on women and internal family migration has tended to conclude that women are usually passive, subordinate, followers, or victims in the migration process because of the nature of their relationship to men. This study focuses on the independent (unsponsored) migrant rather than the corporate mover, which allows us to see how partnered women initiate and benefit from migration because of their sense of control over the process. While some women may still follow men in relocation, partnered women have their own labor-force interests at the destination and relational issues are critical in the migration process. Active participation in migration decision-making by women contributes to greater satisfaction with relocation.
Equivalent Clinical Results of Arthroscopic Single-Row and Double-Row Suture Anchor Repair for Rotator Cuff Tears
Authors: Franceschi Francesco , Ruzzini Laura , Longo Umile Giuseppe , Martina Francesca Maria , Beomonte Zobel Bruno , Maffulli Nicola , Denaro Vincenzo
Published: June 2007

Background

Restoring the anatomical footprint may improve the healing and mechanical strength of repaired tendons. A double row of suture anchors increases the tendon-bone contact area, reconstituting a more anatomical configuration of the rotator cuff footprint.

Hypothesis

There is no difference in clinical and imaging outcome between single-row and double-row suture anchor technique repairs of rotator cuff tears.

Study Design

Randomized controlled trial; Level of evidence, 1.

Methods

The authors recruited 60 patients. In 30 patients, rotator cuff repair was performed with a single-row suture anchor technique (group 1). In the other 30 patients, rotator cuff repair was performed with a double-row suture anchor technique (group 2).

Results

Eight patients (4 in the single-row anchor repair group and 4 in the double-row anchor repair group) did not return at the final follow-up. At the 2-year follow-up, no statistically significant differences were seen with respect to the University of California, Los Angeles score and range of motion values. At 2-year follow-up, postoperative magnetic resonance arthrography in group 1 showed intact tendons in 14 patients, partial-thickness defects in 10 patients, and full-thickness defects in 2 patients. In group 2, magnetic resonance arthrography showed an intact rotator cuff in 18 patients, partial-thickness defects in 7 patients, and full-thickness defects in 1 patient.

Conclusion

Single- and double-row techniques provide comparable clinical outcome at 2 years. A double-row technique produces a mechanically superior construct compared with the single-row method in restoring the anatomical footprint of the rotator cuff, but these mechanical advantages do not translate into superior clinical performance.
Effect of Propylene Carbonate on the Properties of Composite Fiberboard from Wood Fiber Bonded with Renewable Wood Resin
Authors: Sain Mohini M. , Ghosh Arun , Banik Indranil
Published: June 2007

In our previous article, we studied the feasibility of using wood resin in mixture with urea—formaldehyde resin as a binder for the fiberboard composites. In the present article, we have made an attempt to verify the effectiveness of propylene carbonate (PC) as an accelerator on the curing and performance of the composite from the resin mixture. The results demonstrated that the performance of the resulting composite fiberboard cured at lower temperature could be enhanced by addition of propylene carbonate. The composites cured in presence of PC surpassed the minimum requirement of physical properties specified by ANSI-AHA standards. The dosage of PC was optimized to achieve the best combination of composite properties.
From Deliberative to Routine Behaviors: A Cognitively Inspired Action-Selection Mechanism for Routine Behavior Capture
Authors: Chernova Sonia , Arkin Ronald C.
Published: June 2007

Long-term human—robot interaction, especially in the case of humanoid robots, requires an adaptable and varied behavior base. In this paper, we present a method for capturing, or learning, sequential tasks by transferring serial behavior execution from deliberative to routine control. The incorporation of this approach leads to the natural development of complex and varied behaviors, with lower demands for planning, coordination and resources. We demonstrate how this process can be performed autonomously as part of the normal function of the robot, without the need for an explicit learning stage or user guidance. The complete implementation of this algorithm on the Sony QRIO humanoid robot is described.
Sound and vision
Authors: van Leeuwen Theo
Published: June 2007

Experimenting with page layout as a discursive mode, this visual essay offers a brief history of the idea of immersion. It then pays particular attention to the role of sound in immersive experience.
Tarantino the Cartoonist
Authors: Pallant Chris
Published: June 2007

In cinema it is not uncommon to see the interrelation of animation and live action but, despite this, the ascription of characteristics of one medium onto the other has been largely one-dimensional: live action upon animation. The films of Quentin Tarantino, however, illustrate an attribution of a cartoon-like aesthetic in live-action sequences, which the author subsequently terms `cartoonism'. `Cartoonism' and its development have been highlighted in Tarantino's work, showing his continual desire to realize this aesthetic in his own work whilst, ironically, only fully achieving this aesthetic in another's film. The conclusions are illuminating with respect to Tarantino's filmic politics and provide a potential mode of inquiry within film theory.
Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia
Authors: Signer Robert A. J. , Montecino-Rodriguez Encarnacion , Witte Owen N. , McLaughlin Jami , Dorshkind Kenneth
Published: June 2007

Reduced lymphopoiesis during aging contributes to declines in immunity, but little consideration has been given to its effect on the development of hematologic disease. This report demonstrates that age-related defects in lymphopoiesis underlie the myeloid dominance of adult leukemia. Using a murine model of chronic myeloid leukemia, an adult-onset malignancy that arises from transformation of hematopoietic stem cells by the BCR-ABLP210 oncogene, we demonstrate that young bone marrow (BM) cells that were transformed with BCR-ABLP210 initiated both a myeloproliferative disorder (MPD) and B-lymphoid leukemia, whereas BCR-ABLP210–transformed old BM cells recapitulated the human disease by inducing an MPD with rare lymphoid involvement. In addition, the lesser severity of MPDs initiated from old BCR-ABLP210–transduced BM cells revealed unappreciated defects in aged myeloid progenitors. These data demonstrate that aging affects patterns of leukemogenesis and indicate that the effects of senescence on hematopoiesis are more extensive than previously appreciated.
High-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease and implication for its molecular mechanism
Authors: Kawase Takakazu , Morishima Yasuo , Matsuo Keitaro , Kashiwase Koichi , Inoko Hidetoshi , Saji Hiroh , Kato Shunichi , Juji Takeo , Kodera Yoshihisa , Sasazuki Takehiko
Published: June 2007

In allogenic hematopoietic stem-cell transplantation, an effect of HLA locus mismatch in allele level on clinical outcome has been clarified. However, the effect of each HLA allele mismatch combination is little known, and its molecular mechanism to induce acute graft-versus-host disease (aGVHD) remains to be elucidated. A total of 5210 donor-patient pairs who underwent transplantation through Japan Marrow Donor Program were analyzed. All HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles were retrospectively typed in all pairs. The impacts of the HLA allele mismatch combinations and amino acid substitution positions in 6 HLA loci on severe aGVHD were analyzed. A total of 15 significant high-risk HLA allele mismatch combinations and 1 HLA-DRB1-DQB1 linked mismatch combinations (high-risk mismatch) for severe aGVHD were identified, and the number of high-risk mismatches was highly associated with the occurrence of severe aGVHD regardless of the presence of mismatch combinations other than high-risk mismatch. Furthermore, 6 specific amino acid substitution positions in HLA class I were identified as those responsible for severe aGVHD. These findings provide evidence to elucidate the mechanism of aGVHD on the basis of HLA molecule. Furthermore, the identification of high-risk mismatch, that is, nonpermissive mismatch, would be beneficial for the selection of a suitable donor.
Rapid generation of a functional NK-cell compartment
Authors: Prlic Martin , Kamimura Daisuke , Bevan Michael J.
Published: June 2007

Bone marrow transplants are an important therapeutic tool for treating certain types of cancer as well as genetic diseases affecting the hematopoietic system. Until the transferred stem cells differentiate and reconstitute the immune system, recipients are at increased risk from opportunistic infections. We report the rapid generation of a functional natural killer (NK) compartment in lethally irradiated mice that received bone marrow cells from a syngeneic donor by treatment with IL-2/anti–IL-2 antibody complexes. We demonstrate that IL-2 complexes specifically expand the donor but not the host NK population and discuss the implications of this finding in the context of graft-versus-host disease and tumor relapse. Finally, we show that NK cells rapidly generated by IL-2 complexes kill MHC class I–deficient cells effectively in vivo. These data underline the unique therapeutic potential of IL-2 complexes.
160-fold acceleration of the Smith-Waterman algorithm using a field programmable gate array (FPGA)
Authors: Li Isaac TS , Shum Warren , Truong Kevin
Published: June 2007

Background

To infer homology and subsequently gene function, the Smith-Waterman (SW) algorithm is used to find the optimal local alignment between two sequences. When searching sequence databases that may contain hundreds of millions of sequences, this algorithm becomes computationally expensive.

Results

In this paper, we focused on accelerating the Smith-Waterman algorithm by using FPGA-based hardware that implemented a module for computing the score of a single cell of the SW matrix. Then using a grid of this module, the entire SW matrix was computed at the speed of field propagation through the FPGA circuit. These modifications dramatically accelerated the algorithm's computation time by up to 160 folds compared to a pure software implementation running on the same FPGA with an Altera Nios II softprocessor.

Conclusion

This design of FPGA accelerated hardware offers a new promising direction to seeking computation improvement of genomic database searching.
Low major histocompatibility complex class II DQA diversity in the Giant Panda (Ailuropoda melanoleuca)
Authors: Zhu Liang , Ruan Xiang-Dong , Ge Yun-Fa , Wan Qiu-Hong , Fang Sheng-Guo
Published: June 2007

Background

The giant panda (Ailuropoda melanoleuca) is one of the most endangered animals due to habitat fragmentation and loss. Although the captive breeding program for this species is now nearly two decades old, researches on the genetic background of such captive populations, especially on adaptive molecular polymorphism of major histocompatibility complex (MHC), are still limited. In this study, we characterized adaptive variation of the giant panda's MHC DQA gene by PCR amplification of its antigen-recognizing region (i.e. the exon 2) and subsequent single-strand conformational polymorphism (SSCP) and sequence analyses.

Results

The results revealed a low level of DQA exon 2 diversity in this rare animal, presenting 6 alleles from 61 giant panda individuals. The observed polymorphism was restricted to 9 amino acid substitutions, all of which occurred at and adjacent to positions forming the functionally important antigen-binding sites. All the samples were in Hardy-Weinberg proportions. A significantly higher rate of non-synonymous than synonymous substitutions at the antigen-binding sites indicated positive selection for diversity in the locus.

Conclusion

The DQA allelic diversity of giant pandas was low relative to other vertebrates. Nonetheless, the pandas exhibited more alleles in DQA than those in DRB, suggesting the alpha chain genes would play a leading role when coping with certain pathogens and thus should be included in conservation genetic investigation. The microsatellite and MHC loci might predict long-term persistence potential and short-term survival ability, respectively. Consequently, it is recommended to utilize multiple suites of microsatellite markers and multiple MHC loci to detect overall genetic variation in order to design unbiased conservation strategies.