bluuebunny/crossref_metadata_2025 huggingface dataset:
Leishmaniasis
Authors: Piscopo Tonio V , Mallia Azzopardi Charles
Published: February 2007

Epidemiology, disease patterns, immunology, diagnosis, treatment and control measures of leishmaniasis are described. Various issues relating to leishmaniasis are highlighted: the relative lack of importance given to this disease compared with other infections, climate change and its possible impact on extension of endemicity of this infection, and new diagnostic tests which are improving diagnosis, especially in resource poor areas. Other important aspects discussed include the potential for newer oral therapy to change the way this disease is managed; Leishmania–HIV coinfection and groups at risk; and development of an effective vaccine.
Prevalence of coeliac disease in children and adolescents with type 1 diabetes mellitus in a clinic based population
Authors: Goh C , Banerjee K
Published: February 2007

Background

Although the association between type 1 diabetes mellitus (T1DM) and coeliac disease is well known, the presenting features and clinical characteristics of the two diseases when they coexist are less well documented.

Methods

All patients with T1DM attending a paediatric diabetes clinic in London, UK, were screened for coeliac disease by serological testing for coeliac antibodies (antiendomysial and either/both tissue transglutaminase and antigliadin). Antibody positive patients were reviewed and their presenting symptoms, tissue biopsy result and coexisting morbidities investigated. Glycaemic control, growth and the effect of a gluten-free diet on these variables were also evaluated.

Results

Of the 113 patients with T1DM, 7 (6.2%) tested antibody positive. Jejunal biopsy confirmed coeliac disease in 5 of the 7 (4.4%) patients. Coeliac disease presented atypically or silently in the majority of cases with an unpredictable interval between diagnosis of diabetes and coeliac disease presentation. Coeliac disease did not appear to affect growth. Mean glycated haemoglobin (HbA1c) levels were not significantly raised in subjects (9.87%) compared with matched controls without coeliac disease (9.08%) (p = 0.249). Analyses of the effect of a gluten-free diet on growth and HbA1c were limited. Of the seven subjects, two suffered other autoimmune diseases.

Conclusion

Coeliac disease presents atypically and unexpectedly in children and adolescents with T1DM. This, along with the strong association between the two diseases, supports the regular screening of coeliac disease among these patients. The value of a gluten-free diet cannot be commented on from this study alone although other studies show it reduces the risk of complications.
Diabetic and endocrine emergencies
Authors: Kearney T , Dang C
Published: February 2007

Endocrine emergencies constitute only a small percentage of the emergency workload of general doctors, comprising about 1.5% of all hospital admission in England in 2004–5. Most of these are diabetes related with the remaining conditions totalling a few hundred cases at most. Hence any individual doctor might not have sufficient exposure to be confident in their management. This review discusses the management of diabetic ketoacidosis, hyperosmolar hyperglycaemic state, hypoglycaemia, hypercalcaemia, thyroid storm, myxoedema coma, acute adrenal insufficiency, phaeochromocytoma hypertensive crisis and pituitary apoplexy in the adult population.
Is rheumatoid arthritis a disease that starts in the intestine? A pilot study comparing an elemental diet with oral prednisolone
Authors: Podas Thrasyvoulos , Nightingale Jeremy M D , Oldham Roger , Roy S , Sheehan Nicholas J , Mayberry John F
Published: February 2007

Objectives

This pilot study aimed to determine if an elemental diet could be used to treat patients with active rheumatoid arthritis and to compare its effect to that of oral prednisolone.

Methods

Thirty patients with active rheumatoid arthritis were randomly allocated to 2 weeks of treatment with an elemental diet (n = 21) or oral prednisolone 15 mg/day (n = 9). Assessments of duration of early morning stiffness (EMS), pain on a 10 cm visual analog scale (VAS), the Ritchie articular index (RAI), swollen joint score, the Stanford Health Assessment Questionnaire, global patient and physician assessment, body weight, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and haemoglobin, were made at 0, 2, 4 and 6 weeks.

Results

All clinical parameters improved in both groups (p<0.05) except the swollen joint score in the elemental diet group. An improvement of greater than 20% in EMS, VAS and RAI occurred in 72% of the elemental diet group and 78% of the prednisolone group. ESR, CRP and haemoglobin improved in the steroid group only (p<0.05).

Conclusions

An elemental diet for 2 weeks resulted in a clinical improvement in patients with active rheumatoid arthritis, and was as effective as a course of oral prednisolone 15 mg daily in improving subjective clinical parameters. This study supports the concept that rheumatoid arthritis may be a reaction to a food antigen(s) and that the disease process starts within the intestine.
An audit of “do not attempt resuscitation” decisions in two district general hospitals: do current guidelines need changing?
Authors: Harris Dylan , Davies Rachel
Published: February 2007

Introduction

Doctors in all specialties are involved in making “do not attempt resuscitation” (DNAR) decisions; this can be a difficult and challenging process. Guidelines exist to provide an ethical and legal framework for the process and documentation of these decisions.

Objective

To audit the documentation of resuscitation decisions in a sample of medical inpatients from two district general hospitals.

Method

A retrospective case note audit of 50 medical inpatients, in which a DNAR decision had been made (28 from hospital 1, 22 from hospital 2).

Results

Average age was 78.9 years (48% male:52% female). In both hospitals DNAR decisions were usually discussed with relatives (84%), documented in nursing notes (100%) and made by senior team members (90%). Although the decision was usually dated and clearly documented (98%), abbreviations were commonly used in hospital 2 (45.5% vs 0% in hospital 1, p<0.05). Decisions regarding other treatment were not consistently documented (78.6% and 72.7%, respectively) and there was little evidence that decisions were reviewed (14.3% and 31.8%). The decision was rarely discussed with the patient (6% of all patients), although 66% of patients were not in a position to have a discussion.

Conclusions

Specific forms for recording DNAR decisions improve the clarity of documentation. Current recommendations to discuss resuscitation with patients are controversial and not followed. However, many patients are not in a position to hold a discussion when the need arises and the guidelines should advocate early discussion during a hospital admission in patients where this is appropriate, prior discussion with family and/or wider use of advanced directives.
PARALLEL DELAUNAY REFINEMENT: ALGORITHMS AND ANALYSES
Authors: SPIELMAN DANIEL A. , TENG SHANG-HUA , ÜNGÖR ALPER
Published: February 2007

We present a parallel Delaunay refinement algorithm for generating well-shaped meshes in both two and three dimensions. Like its sequential counterparts, the parallel algorithm iteratively improves the quality of a mesh by inserting new points, the Steiner points, into the input domain while maintaining the Delaunay triangulation. The Steiner points are carefully chosen from a set of candidates that includes the circumcenters of poorly-shaped triangular elements. We introduce a notion of independence among possible Steiner points that can be inserted simultaneously during Delaunay refinements and show that such a set of independent points can be constructed efficiently and that the number of parallel iterations is O( log 2Δ), where Δ is the spread of the input — the ratio of the longest to the shortest pairwise distances among input features. In addition, we show that the parallel insertion of these set of points can be realized by sequential Delaunay refinement algorithms such as by Ruppert's algorithm in two dimensions and Shewchuk's algorithm in three dimensions. Therefore, our parallel Delaunay refinement algorithm provides the same shape quality and mesh-size guarantees as these sequential algorithms. For generating quasi-uniform meshes, such as those produced by Chew's algorithms, the number of parallel iterations is in fact O( log Δ).

To the best of our knowledge, our algorithm is the first provably polylog(Δ) time parallel Delaunay-refinement algorithm that generates well-shaped meshes of size within a constant factor of the best possible.
A FAST HYBRID ALGORITHM FOR MULTICAST ROUTING IN WIRELESS NETWORKS
Authors: AL-SHARHAN S. , GUEAIEB W.
Published: February 2007

This paper tackles the issue of constrained multicast routing in wireless networks using a hybrid soft computing-based algorithm. Recent developments in multimedia applications and the dynamic and rapidly changed environment of the wireless networks make the constrained multicast routing a real challenge. The problem can be formulated as minimizing a multicast tree cost under several constraints or Quality of Service (QoS) metrics. This problem has been proven to be NP-complete. The proposed hybrid algorithm is based on a population based incremental learning algorithm that combines in an efficient way the features of genetic algorithms and competitive learning. Experimental results show that, in most cases, the proposed algorithm yields better solutions than other heuristic algorithms proposed in the literature.
AN IMPLEMENTATION OF METRICS EXTRACTION AND ANALYZER TOOL
Authors: QUAH TONG-SENG
Published: February 2007

Nowadays, developers use N-tier application architecture which is a flexible and reusable structure for distribution to any number of client interfaces. In this study, we have implemented metrics extraction and analyzer tool for Business Tier and Data Access Tier source codes. We used existing object-oriented metrics and complexity software metrics as proposed for Business Tier code1,3. We use a set of metrics for the Data Access Tier that has been proposed in our previous study2. The primary aim of the implementation of the metric extraction and analyzer tool is to facilitate generation of software metrics which are used as independent variables in software quality prediction models. A secondary goal is to gather and present information on the attributes of source code to assist the programmers in managing the software projects. This tool is able to generate the principal components, correlation analysis report and descriptive statistics report. These analysis reports are essential reports for the study of software measurement and software quality management.
A SURVEY OF BOTT–TAUBES INTEGRATION
Authors: VOLIĆ ISMAR
Published: February 2007

It is well-known that certain combinations of configuration space integrals defined by Bott and Taubes [11] produce cohomology classes of spaces of knots. The literature surrounding this important fact, however, is somewhat incomplete and lacking in detail. The aim of this paper is to fill in the gaps as well as summarize the importance of these integrals.
THREE-PAGE ENCODING AND COMPLEXITY THEORY FOR SPATIAL GRAPHS
Authors: KURLIN V.
Published: February 2007

A finitely presented semigroup RSGnis constructed for n ≥ 2. The centre of RSGnencodes uniquely up to rigid ambient isotopy in 3-space all nonoriented spatial graphs with vertices of degree ≤ n. This encoding is obtained by using three-page embeddings of graphs into the three-page book T × I, where T is the cone on three points, and I is the unit segment. The notion of the three-page complexity for spatial graphs is introduced via three-page embeddings. This complexity satisfies the properties of finiteness and additivity under natural operations.
A FORMAL HOLONIC FRAMEWORK WITH PROVED SELF-ORGANIZING CAPABILITIES
Authors: RODRIGUEZ SEBASTIAN , HILAIRE VINCENT , GRUER PABLO , KOUKAM ABDER
Published: February 2007

Numerous works aim to design agents and multi-agent systems architectures in order to enable cooperation and coordination between agents. Most of them use organizational structures or societies metaphor to define the MAS architecture. It seems improbable that a rigid unscalable organization could handle a real world problem, so it is interesting to provide agents with abilities to self-organize according to problem's objectives and environment dynamics. We have chosen the holonic paradigm to provide these abilities to agents. Holons are recursive self-similar entities which are organized in an emergent society — an holarchy. The aim of this paper is to present a formally specified framework for holonic MAS which allows agents to self-organize. The framework is illustrated by an example drawn from a real world problem. Some pertinent properties concerning the self-organizing capabilities of this framework are then proved.
FUZZY PRIME AND SEMIPRIME S-SUBACTS OVER MONOIDS
Authors: AHSAN J. , SAIFULLAH K. , SHABIR M.
Published: February 2007

In this paper, we introduce the notions of fuzzy prime and fuzzy semiprime S-subacts, where S is a monoid with a zero and S-acts are representations of S. We establish their basic properties and prove some fundamental results in a fuzzy context, analogous to the results in ordinary semigroups and S-acts. It is shown, among other results, that if a fuzzy right S-subact is fuzzy irreducible, then the difference between fuzzy prime and fuzzy semiprime disappears.
Tracheary Element Differentiation
Authors: Turner Simon , Gallois Patrick , Brown David
Published: February 2007

Tracheary elements (TEs) are cells in the xylem that are highly specialized for transporting water and solutes up the plant. TEs undergo a very well-defined process of differentiation that involves specification, enlargement, patterned cell wall deposition, programmed cell death and cell wall removal. This process is coordinated such that adjacent TEs are joined together to form a continuous network. Expression studies on model systems as diverse as trees and cell cultures have contributed to providing a flood of candidate genes with potential roles in TE differentiation. Analysis of some of these genes has yielded important information on processes such as patterned secondary cell wall deposition. The current challenge is to continue this functional analysis and to use these data and build an integrated model of TE development.
Tetrapyrrole Biosynthesis in Higher Plants
Authors: Tanaka Ryouichi , Tanaka Ayumi
Published: February 2007

Tetrapyrroles play vital roles in various biological processes, including photosynthesis and respiration. Higher plants contain four classes of tetrapyrroles, namely, chlorophyll, heme, siroheme, and phytochromobilin. All of the tetrapyrroles are derived from a common biosynthetic pathway. Here we review recent progress in the research of tetrapyrrole biosynthesis from a cellular biological view. The progress consists of biochemical, structural, and genetic analyses, which contribute to our understanding of how the flow and the synthesis of tetrapyrrole molecules are regulated and how the potentially toxic intermediates of tetrapyrrole synthesis are maintained at low levels. We also describe interactions of tetrapyrrole biosynthesis and other cellular processes including the stay-green events, the cell-death program, and the plastid-to-nucleus signal transduction. Finally, we present several reports on attempts for agricultural and horticultural applications in which the tetrapyrrole biosynthesis pathway was genetically modified.
The Plant Heterotrimeric G-Protein Complex
Authors: Temple Brenda R. S. , Jones Alan M.
Published: February 2007

Heterotrimeric G-protein complexes couple extracellular signals via cell surface receptors to downstream enzymes called effectors. Heterotrimeric G-protein complexes, together with their cognate receptors and effectors, operate at the apex of signal transduction. In plants, the number of G-protein complex components is dramatically less than in other multicellular eukaryotes. An understanding of how multiple signals propagate transduction through the G-protein node can be found in the unique structural and kinetic properties of the plant heterotrimeric G-protein complex. This review addresses these unique features and speculates on why the repertoire of G-protein signaling elements is dramatically simpler than that in all other multicellular eukaryotes.
Gibberellin Receptor and Its Role in Gibberellin Signaling in Plants
Authors: Ueguchi-Tanaka Miyako , Nakajima Masatoshi , Motoyuki Ashikari , Matsuoka Makoto
Published: February 2007

Gibberellins (GAs) are a large family of tetracyclic, diterpenoid plant hormones that induce a wide range of plant growth responses. It has been postulated that plants have two types of GA receptors, including soluble and membrane-bound forms. Recently, it was determined that the rice GIBBERELLIN INSENSITIVE DWARF1 (GID1) gene encodes an unknown protein with similarity to the hormone-sensitive lipases that has high affinity only for biologically active GAs. Moreover, GID1 binds to SLR1, a repressor of GA signaling, in a GA-dependent manner in yeast cells. Based on these observations, it has been concluded that GID1 is a soluble receptor mediating GA signaling in rice. More recently, Arabidopsis thaliana was found to have three GID1 homologs, AtGID1a, b, and c, all of which bind GA and interact with the five Arabidopsis DELLA proteins.
Populus: A Model System for Plant Biology
Authors: Jansson Stefan , Douglas Carl J.
Published: February 2007

With the completion of the Populus trichocarpa genome sequence and the development of various genetic, genomic, and biochemical tools, Populus now offers many possibilities to study questions that cannot be as easily addressed in Arabidopsis and rice, the two prime model systems of plant biology and genomics. Tree-specific traits such as wood formation, long-term perennial growth, and seasonality are obvious areas of research, but research in other areas such as control of flowering, biotic interactions, and evolution of adaptive traits is enriched by adding a tree to the suite of model systems. Furthermore, the reproductive biology of Populus (a dioeceous wind-pollinated long-lived tree) offers both new possibilities and challenges in the study and analysis of natural genetic and phenotypic variation. The relatively close phylogenetic relationship of Populus to Arabidopsis in the Eurosid clade of Eudicotyledonous plants aids in comparative functional studies and comparative genomics, and has the potential to greatly facilitate studies on genome and gene family evolution in eudicots.
Hidden Branches: Developments in Root System Architecture
Authors: Osmont Karen S. , Sibout Richard , Hardtke Christian S.
Published: February 2007

The root system is fundamentally important for plant growth and survival because of its role in water and nutrient uptake. Therefore, plants rely on modulation of root system architecture (RSA) to respond to a changing soil environment. Although RSA is a highly plastic trait and varies both between and among species, the basic root system morphology and its plasticity are controlled by inherent genetic factors. These mediate the modification of RSA, mostly at the level of root branching, in response to a suite of biotic and abiotic factors. Recent progress in the understanding of the molecular basis of these responses suggests that they largely feed through hormone homeostasis and signaling pathways. Novel factors implicated in the regulation of RSA in response to the myriad endogenous and exogenous signals are also increasingly isolated through alternative approaches such as quantitative trait locus analysis.
Cyclic Electron Transport Around Photosystem I: Genetic Approaches
Authors: Shikanai Toshiharu
Published: February 2007

The light reactions in photosynthesis convert light energy into chemical energy in the form of ATP and drive the production of NADPH from NADP+. The reactions involve two types of electron flow in the chloroplast. While linear electron transport generates both ATP and NADPH, photosystem I cyclic electron transport is exclusively involved in ATP synthesis. The physiological significance of photosystem I cyclic electron transport has been underestimated, and our knowledge of the machineries involved remains very limited. However, recent genetic approaches using Arabidopsis thaliana have clarified the essential functions of this electron flow in both photoprotection and photosynthesis. Based on several lines of evidence presented here, it is necessary to reconsider the fundamental mechanisms of chloroplast energetics.
β-Arrestins and Cell Signaling
Authors: DeWire Scott M. , Ahn Seungkirl , Lefkowitz Robert J. , Shenoy Sudha K.
Published: February 2007

Upon their discovery, β-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization. Surprisingly, recent evidence shows that β-arrestins can also function to activate signaling cascades independently of G protein activation. By serving as multiprotein scaffolds, the β-arrestins bring elements of specific signaling pathways into close proximity. β-Arrestin regulation has been demonstrated for an ever-increasing number of signaling molecules, including the mitogen-activated protein kinases ERK, JNK, and p38 as well as Akt, PI3 kinase, and RhoA. In addition, investigators are discovering new roles for β-arrestins in nuclear functions. Here, we review the signaling capacities of these versatile adapter molecules and discuss the possible implications for cellular processes such as chemotaxis and apoptosis.
Nuclear translocation of calcineurin Aβ but not calcineurin Aα by platelet-derived growth factor in rat aortic smooth muscle
Authors: Jabr Rita I. , Wilson Andrew J. , Riddervold Marilyn H. , Jenkins Alex H. , Perrino Brian A. , Clapp Lucie H.
Published: February 2007

Calcineurin regulates the proliferation of many cell types through activation of the nuclear factor of activated T cells (NFAT). Two main isoforms of the calcineurin catalytic subunit [calcineurin A (CnA)α and CnAβ] have been identified, although their expression and function are largely unknown in smooth muscle. Western blot analysis and confocal imaging were performed in freshly isolated and cultured rat aortic myocytes to identify these CnA isoforms and elucidate the effect of PDGF on their cellular distribution and interaction with NFAT isoforms. CnAα and CnAβ isoforms displayed differential cellular distribution, with CnAα being evenly distributed between the nucleus and cytosol and CnAβ being restricted to the cytosol. In contrast with the rat brain, we found no evidence for particulate/membrane localization of calcineurin. PDGF caused significant nuclear translocation of CnAβ and induced smooth muscle cell proliferation, with both effects being abrogated by the calcineurin inhibitor cyclosporin A, the novel NFAT inhibitors A-285222 and inhibitor of NFAT-calcineurin association-6, and the adenylyl cyclase activator forskolin. PDGF also caused cyclosporin A-sensitive translocation of NFATc3, with no apparent effect on either CnAα or NFATc1 distribution. Moreover, ∼87% of nuclear CnAβ was found to colocalize with NFATc3, consistent with the finding that CnAβ bound more avidly than CnAα to a glutathione S-transferase-NFATc3 fusion protein. Based on their differential distribution in aortic muscle, our results suggest that CnAα and CnAβ are likely to have different cellular functions. However, CnAβ appears to be specifically activated by PDGF, and we postulate that calcineurin-dependent nuclear translocation of NFATc3 is involved in smooth muscle proliferation induced by this mitogen.
Dual regulation of the ATP-sensitive potassium channel by caffeine
Authors: Mao Xia , Chai Yongping , Lin Yu-Fung
Published: February 2007

ATP-sensitive potassium (KATP) channels couple cellular metabolic status to changes in membrane electrical properties. Caffeine (1,2,7-trimethylxanthine) has been shown to inhibit several ion channels; however, how caffeine regulates KATPchannels was not well understood. By performing single-channel recordings in the cell-attached configuration, we found that bath application of caffeine significantly enhanced the currents of Kir6.2/SUR1 channels, a neuronal/pancreatic KATPchannel isoform, expressed in transfected human embryonic kidney (HEK)293 cells in a concentration-dependent manner. Application of nonselective and selective phosphodiesterase (PDE) inhibitors led to significant enhancement of Kir6.2/SUR1 channel currents. Moreover, the stimulatory action of caffeine was significantly attenuated by KT5823, a specific PKG inhibitor, and, to a weaker extent, by BAPTA/AM, a membrane-permeable Ca2+chelator, but not by H-89, a selective PKA inhibitor. Furthermore, the stimulatory effect was completely abrogated when KT5823 and BAPTA/AM were co-applied with caffeine. In contrast, the activity of Kir6.2/SUR1 channels was decreased rather than increased by caffeine in cell-free inside-out patches, while tetrameric Kir6.2LRKR368/369/370/371AAAA channels were suppressed regardless of patch configurations. Caffeine also enhanced the single-channel currents of recombinant Kir6.2/SUR2B channels, a nonvascular smooth muscle KATPchannel isoform, although the increase was smaller. Moreover, bidirectional effects of caffeine were reproduced on the KATPchannel present in the Cambridge rat insulinoma G1 (CRI-G1) cell line. Taken together, our data suggest that caffeine exerts dual regulation on the function of KATPchannels: an inhibitory regulation that acts directly on Kir6.2 or some closely associated regulatory protein(s), and a sulfonylurea receptor (SUR)-dependent stimulatory regulation that requires cGMP-PKG and intracellular Ca2+-dependent signaling.
Developmentally regulated tumor necrosis factor-α induced nuclear factor-κB activation in intestinal epithelium
Authors: Claud Erika C. , Zhang Xiaoqiong , Petrof Elaine O. , Sun Jun
Published: February 2007

Premature infants are susceptible to many conditions that are inflammatory in nature. For this patient population, which is expecting the intrauterine environment, pathways necessary for fetal life and development may not have completed the transitions necessary for extrauterine life. In this study, responses to tumor necrosis factor-α were compared in human fetal and adult intestinal epithelial cell lines along with preweaned and postweaned mouse intestinal sections to identify a potential developmental difference that may explain the heightened inflammatory response of preterm infants. The nuclear factor-κB (NF-κB) pathway regulates a wide variety of genes involved in immune and inflammatory processes. We report that, compared with adult intestinal epithelial cells, immature intestinal epithelial cells have increased NF-κB activity associated with increased NF-κB-DNA binding and transcriptional activity. This increased activity appears due to inadequate inhibition of signaling leading to NF-κB activation since there is also increased phosphorylation, ubiquitination, and degradation of the inhibitor of NF-κB in conjunction with decreased baseline expression and delayed resynthesis of this inhibitor. Thus we demonstrate a potential mechanism for the heightened inflammatory response of immature intestinal epithelial cells.
ERK activation contributes to regulation of spontaneous contractile tone via superoxide anion in isolated rat aorta of angiotensin II-induced hypertension
Authors: Ding Lili , Chapman Alexander , Boyd Ryan , Wang Hui Di
Published: February 2007

Arteries from hypertensive animals and humans have increased spontaneous tone. Increased superoxide anion (superoxide) contributes to elevated blood pressure (BP) and spontaneous tone in hypertension. The association between the extracellular signaling-regulated kinase 1/2 (ERK1/2)-mitogen-activated protein kinase (MAPK) signaling pathway and generation of superoxide and spontaneous tone in isolated aorta was studied in angiotensin II (ANG II)-infused hypertensive (HT) rats. Systolic BP, phosphorylation of ERK, aortic superoxide formation, and aortic spontaneous tone were compared in sham normotensive and HT rats. Infusion of ANG II (0.5 mg·kg−1·day−1 for 6 days) significantly elevated the systolic BP ( P < 0.01). The phosphorylation of ERK1/2 vs. total ERK1/2 in thoracic aorta was enhanced, and superoxide was increased in the HT vs. the sham group ( P < 0.01). Spontaneous tone developed in the HT group, but not in the normotensive group. MAPK/ERK1/2 (MEK1/2)-ERK1/2 signaling pathway inhibitors, PD-98059 (10 μmol/l), and U-0126 (10 μmol/l), significantly reduced the phosphorylation of ERK1/2, superoxide generation ( P < 0.01), and spontaneous tone ( P < 0.01) in HT. These findings suggest that ANG II infusion induces the production of superoxide and spontaneous tone and that both are dependent on ERK-MAPK activation. In endothelium-denuded aorta, however, MEK1/2 inhibitors did not inhibit the spontaneous tone, even though they significantly reduced superoxide generation similar to endothelium-intact aorta. These data suggest that inhibition of ERK1/2 signaling pathway, via PD-98059 or U-0126, may regulate spontaneous tone in an endothelium-dependent manner. In conclusion, these findings support the importance of the ERK1/2 signaling pathway in modulating vascular oxidative stress and subsequently mediating spontaneous tone in HT.
A modular instrument for exploring the mechanics of cardiac myocytes
Authors: Garcia-Webb M. G. , Taberner A. J. , Hogan N. C. , Hunter I. W.
Published: February 2007

The cardiac ventricular myocyte is a key experimental system for exploring the mechanical properties of the diseased and healthy heart. Millions of primary myocytes, which remain viable for 4–6 h, can be readily isolated from animal models. However, currently available instrumentation allows the mechanical properties of only a few physically loaded myocytes to be explored within 4–6 h. Here we describe a modular and inexpensive prototype instrument that could form the basis of an array of devices for probing the mechanical properties of single mammalian myocytes in parallel. This device would greatly increase the throughput of scientific experimentation and could be applied as a high-content screening instrument in the pharmaceutical industry. The instrument module consists of two independently controlled Lorentz force actuators-force transducers in the form of 0.025 × 1 × 5 mm stainless steel cantilevers with 0.5 m/N compliance and 360-Hz resonant frequency. Optical position sensors focused on each cantilever provide position and force resolution of <1 nm/√Hz and <2 nN/√Hz, respectively. The motor structure can produce peak displacements and forces of ±200 μm and ±400 μN, respectively. Custom Visual Basic.Net software provides data acquisition, signal processing, and digital control of cantilever position. The functionality of the instrument was demonstrated by implementation of novel methodologies for loading and attaching healthy mammalian ventricular myocytes to the force sensor and actuator and use of stochastic system identification techniques to measure their passive dynamic stiffness at various sarcomere lengths.
Effects of early afterdepolarizations on reentry in cardiac tissue: a simulation study
Authors: Huffaker Ray B. , Weiss James N. , Kogan Boris
Published: February 2007

Early afterdepolarizations (EADs) are classically generated at slow heart rates when repolarization reserve is reduced by genetic diseases or drugs. However, EADs may also occur at rapid heart rates if repolarization reserve is sufficiently reduced. In this setting, spontaneous diastolic sarcoplasmic reticulum (SR) Ca release can facilitate cellular EAD formation by augmenting inward currents during the action potential plateau, allowing reactivation of the window L-type Ca current to reverse repolarization. Here, we investigated the effects of spontaneous SR Ca release-induced EADs on reentrant wave propagation in simulated one-, two-, and three-dimensional homogeneous cardiac tissue using a version of the Luo-Rudy dynamic ventricular action potential model modified to increase the likelihood of these EADs. We found: 1) during reentry, nonuniformity in spontaneous SR Ca release related to subtle differences in excitation history throughout the tissue created adjacent regions with and without EADs. This allowed EADs to initiate new wavefronts propagating into repolarized tissue; 2) EAD-generated wavefronts could propagate in either the original or opposite direction, as a single new wave or two new waves, depending on the refractoriness of tissue bordering the EAD region; 3) by suddenly prolonging local refractoriness, EADs caused rapid rotor displacement, shifting the electrical axis; and 4) rapid rotor displacement promoted self-termination by collision with tissue borders, but persistent EADs could regenerate single or multiple focal excitations that reinitiated reentry. These findings may explain many features of Torsades des pointes, such as perpetuation by focal excitations, rapidly changing electrical axis, frequent self-termination, and occasional degeneration to fibrillation.
MLCK210 gene knockout or kinase inhibition preserves lung function following endotoxin-induced lung injury in mice
Authors: Rossi Janet L. , Velentza Anastasia V. , Steinhorn David M. , Watterson D. Martin , Wainwright Mark S.
Published: February 2007

Barrier dysfunction, involving the endothelium or epithelium, is implicated in the pathophysiology of many disease states, including acute and ventilator-associated lung injury. Evidence from cell culture, in vivo and clinical studies, has identified myosin light chain kinase as a drug discovery target for such diseases. Here, we measured disease-relevant end points to test the hypothesis that inhibition of myosin light chain kinase is a potential therapeutic target for treatment of barrier dysfunction resulting from acute lung injury. We used a combined gene knockout and chemical biology approach with an in vivo intact lung injury model. We showed that inhibition of myosin light chain kinase protects lung function, preserves oxygenation, prevents acidosis, and enhances survival after endotoxin exposure with subsequent mechanical ventilation. This protective effect provided by the small molecule inhibitor of myosin light chain kinase is present when the inhibitor is administered during a clinically relevant injury paradigm after endotoxin exposure. Treatment with inhibitor confers additional protection against acute lung injury to that provided by a standard protective mode of ventilation. These results support the hypothesis that myosin light chain kinase is a potential therapeutic target for acute lung injury and provide clinical end points of arterial blood gases and pulmonary compliance that facilitate the direct extrapolation of these studies to measures used in critical care medicine.
Early feeding of carnivorous rainbow trout (Oncorhynchus mykiss) with a hyperglucidic diet during a short period: effect on dietary glucose utilization in juveniles
Authors: Geurden I. , Aramendi M. , Zambonino-Infante J. , Panserat S.
Published: February 2007

Based on the concept of nutritional programming in higher vertebrates, we tested whether an acute hyperglucidic stimulus during early life could induce a long-lasting effect on carbohydrate utilization in carnivorous rainbow trout. The trout were fed a hyperglucidic diet (60% dextrin) at two early stages of development: either at first feeding (3 days, stimulus 1) or after yolk absorption (5 days, stimulus 2). Before and after the hyperglucidic stimulus, they received a commercial diet until juvenile stage (>10 g). Fish that did not experience the hyperglucidic stimuli served as controls. The short- and long-term effects of the stimuli were evaluated by measuring the expression of five key genes involved in carbohydrate utilization: α-amylase, maltase (digestion), sodium-dependent glucose cotransporter (SGLT1; intestinal glucose transport), and glucokinase and glucose-6-phosphatase, involved in the utilization and production of glucose, respectively. The hyperglucidic diet rapidly increased expressions of maltase, α-amylase, and glucokinase in stimulus 1 fish and only of maltase in stimulus 2 fish, probably because of a lower plasticity at this later stage of development. In the final challenge test with juveniles fed a 25% dextrin diet, both digestive enzymes were upregulated in fish that had experienced the hyperglucidic stimulus at first feeding, confirming the possibility of modification of some long-term physiological functions in rainbow trout. In contrast, no persistent molecular adaptations were found for the genes involved in glucose transport or metabolism. In addition, growth and postprandial glycemia were unaffected by the stimuli. In summary, our data show that a short hyperglucidic stimulus during early trout life may permanently influence carbohydrate digestion.
Transforming growth factor-β in the brain is activated by exercise and increases mobilization of fat-related energy substrates in rats
Authors: Shibakusa Tetsuro , Mizunoya Wataru , Okabe Yuki , Matsumura Shigenobu , Iwaki Yoko , Okuno Alato , Shibata Katsumi , Inoue Kazuo , Fushiki Tohru
Published: February 2007

We have recently reported that inhibition of transforming growth factor (TGF)-β in the brain reduced fat-related energy substrates concentrations in response to exercise. We investigated the relevance between the mobilization of fat-related energy substrates (nonesterified fatty acid and ketone bodies) during exercise and the effects of TGF-β in the brain. Low-intensity exercise was simulated by contraction of the hindlimbs, induced by electrical stimulation at 2 Hz in anesthetized rats (Sim-Ex). As with actual exercise, it was confirmed that mobilization of carbohydrate-related energy substrates (glucose and lactic acid) occurred immediately after the onset of Sim-Ex, and mobilization of fat-related energy substrates followed thereafter. The timing of mobilization of fat-related substrates corresponded to that of the increase in TGF-β in cerebrospinal fluid (CSF) in Sim-Ex. The level of TGF-β in CSF significantly increased after 10 min of Sim-Ex and remained elevated until 30 min of Sim-Ex. Intracisternal administration of TGF-β caused rapid mobilization of fat-related energy substrates. Meanwhile, there were no effects on the changes in carbohydrate-related substrates. The levels of catecholamines were slightly elevated after TGF-β administration, and, although not significantly in statistical terms, we consider that at least a part of TGF-β signal was transducted via the sympathetic nervous system because of these increases. These data indicate that TGF-β in the brain is closely related to the mobilization of fat-related energy substrates during low-intensity exercise. We hypothesized that the central nervous system plays a role in the regulation of energy metabolism during low-intensity exercise and this may be mediated by TGF-β.
Development of systemic arterial mechanical properties from infancy to adulthood interpreted by four-element windkessel models
Authors: Burattini Roberto , Di Salvia Paola Oriana
Published: February 2007

Aortic impedance data of infants, children and adults (age range 0.8–54 yr), previously reported by others, were interpreted by means of three alternative four-element windkessel models: W4P, W4S, and IVW. The W4P and W4S are derived from the three-element windkessel (W3) by connecting an inertance ( L) in parallel or in series, respectively, with the aortic characteristic resistance ( Rc). In the IVW, L is connected in series with a viscoelastic windkessel (VW). The W4S and IVW (same input impedance) fit the data best. The W4S, however, suffers from the assumption that Rc is part of total peripheral resistance ( Rp). The IVW model offers a new paradigm for interpretation of resistive properties in terms of viscous ( Rd) properties of vessel wall motion, distinguished from Rp. Results indicated that rapid reduction of Rd/ Rp during early development is functional to modulation of decay time constant (τd) of pressure in diastole, such that normalization over heart period (τd/T) is independent of body size. Estimates of total arterial compliance ( C) vs. age were fitted by a bell-shaped curve with a maximum at 33 yr. With body weight (BW) factored out by normalization, the C/BW data scattered about a bell-shaped curve centered at 66 mmHg. Inertance was significantly higher in pediatric patients than in adults, in accordance with a lower cross-sectional area of the vasculature, commensurate to a lower aortic flow. Changes of arterial properties appear functional to control the ratio of pulsatile power to active power and keep arterial efficiency as high as 97% in infants and children.
Tonic-to-phasic shift of lumbo-pelvic muscle activity during 8 weeks of bed rest and 6-months follow up
Authors: Belavý Daniel L. , Richardson Carolyn A. , Wilson Stephen J. , Felsenberg Dieter , Rittweger Jörn
Published: February 2007

Prior motor control studies in unloading have shown a tonic-to-phasic shift in muscle activation, particularly in the short extensors. Tonic muscle activity is considered critical for normal musculoskeletal function. The shift from tonic-to-phasic muscle activity has not been systematically studied in humans in unloading nor at the lumbo-pelvic (LP) region. Ten healthy young male subjects underwent 8 wk of bed rest with 6-mo follow up as part of the “Berlin Bed-Rest Study.” A repetitive knee movement model performed in the prone position is used to stimulate tonic holding LP muscle activity, as measured by superficial EMG. Tonic and phasic activation patterns were quantified by relative height of burst vs. baseline electromyographic linear-envelope signal components. Statistical analysis shows a shift toward greater phasic activity during bed rest and follow up ( P < 0.001) with a significant interaction across muscles ( P < 0.001) specifically affecting the short lumbar extensors. These changes appear unrelated to skill acquisition over time ( P all ≥0.196). This change of a shift from tonic LP muscle activation to phasic is in line with prior research on the effects of reduced weight bearing on motor control.
Effects of Maintaining Touch Contact on Predictive and Reactive Balance
Authors: Johannsen Leif , Wing Alan M. , Hatzitaki Vassilia
Published: February 2007

Light touch contact between the body and an environmental referent reduces fluctuations of center of pressure (CoP) in quiet standing although the contact forces are insufficient to provide significant forces to stabilize standing balance. Maintenance of upright standing posture (with light touch contact) may include both predictive and reactive components. Recently Dickstein et al. (2003) demonstrated that reaction to temporally unpredictable displacement of the support surface was affected by light touch raising the question whether light touch effects also occur with predictable disturbance to balance. We examined the effects of shoulder light touch on SD of CoP rate (dCoP) during balance perturbations associated with forward sway induced by pulling on (voluntary), or being pulled by (reactive), a hand-held horizontal load. Prior to perturbation, SD dCoP was lower with light touch, corresponding to previous findings. Immediately after perturbation, SD dCoPAPwas greater with light touch in the case of voluntary pull, whereas no difference was found for reflex pull. However, in the following time course, light touch contact again resulted in a significantly lower SD dCoP and faster stabilization of SD dCoP. We conclude that shoulder light touch contact affects immediate postural responses to voluntary pull but also stabilization after voluntary and reflex perturbation. We suggest that in voluntary perturbation CoP fluctuations are differentially modulated in anterioposterior and mediolateral directions to maintain light touch, which not only provides augmented sensory feedback about body self-motion, but may act as a “constraint” to the postural control system when preparing postural adjustments.
Two-Photon Calcium Imaging of Network Activity in XFP-Expressing Neurons in the Mouse
Authors: Wilson Jennifer M. , Dombeck Daniel A. , Díaz-Ríos Manuel , Harris-Warrick Ronald M. , Brownstone Robert M.
Published: February 2007

Fluorescent protein (XFP) expression in postnatal neurons allows the anatomical and physiological investigation of identified subpopulations of interneurons with established techniques. However, the spatiotemporal pattern of activity of these XFP neurons within a network and their role in the functional output of the network are more challenging issues to investigate. Here we apply two-photon excitation laser scanning microscopy to mouse spinal cord locomotor networks and present the methodology by which calcium activity can be recorded in XFP-expressing neurons. Such activity can be studied both in relation to neighboring non-XFP neurons in a spinal cord slice preparation and in relation to functional locomotor output monitored by ventral root activity in the intact in vitro spinal cord. Thus the network properties and functional correlates with locomotion of identified populations of interneurons can be studied simultaneously.
Tumor-Suppressive Effects of Pannexin 1 in C6 Glioma Cells
Authors: Lai Charles P.K. , Bechberger John F. , Thompson Roger J. , MacVicar Brian A. , Bruzzone Roberto , Naus Christian C.
Published: February 2007

Mammalian gap junction proteins, connexins, have long been implicated in tumor suppression. Recently, a novel family of proteins named pannexins has been identified as the mammalian counterpart of the invertebrate gap junction proteins, innexins. To date, pannexin 1 (Panx1) and pannexin 2 (Panx2) mRNAs are reported to be expressed in the brain. Most neoplastic cells, including rat C6 gliomas, exhibit reduced connexin expression, aberrant gap junctional intercellular communication (GJIC), and an increased proliferation rate. When gap junctions are up-regulated by transfecting C6 cells with connexin43, GJIC is restored and the proliferation is reduced. In this study, we examined the tumor-suppressive effects of Panx1 expression in C6 cells. Reverse transcription-PCR analysis revealed that C6 cells do not express any of the pannexin transcripts, whereas its nontumorigenic counterpart, rat primary astrocytes, exhibited mRNAs for all three pannexins. On generation of stable C6 transfectants with tagged Panx1 [myc or enhanced green fluorescent protein (EGFP)], a localization of Panx1 expression to the Golgi apparatus and plasma membrane was observed. In addition, Panx1 transfectants exhibited a flattened morphology, which differs greatly from the spindle-shaped control cells (EGFP only). Moreover, Panx1 expression increased gap junctional coupling as shown by the passage of sulforhodamine 101. Finally, we showed that stable expression of Panx1 in C6 cells significantly reduced cell proliferation in monolayers, cell motility, anchorage-independent growth, and in vivo tumor growth in athymic nude mice. Altogether, we conclude that the loss of pannexin expression may participate in the development of C6 gliomas, whereas restoration of Panx1 plays a tumor-suppressive role. [Cancer Res 2007;67(4):1545–54]