bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting altered postural control after cerebral concussion in athletes with normal postural stability
Authors: Cavanaugh J T , Guskiewicz K M , Giuliani C , Marshall S , Mercer V , Stergiou N
Published: October 2005

Objective:To determine if approximate entropy (ApEn), a regularity statistic from non-linear dynamics, could detect changes in postural control during quiet standing in athletes with normal postural stability after cerebral concussion.

Methods:The study was a retrospective, case series analysis of centre of pressure (COP) data collected during the Sensory Organization Test (SOT) from NCAA Division I (USA) athletes prior to and within 48 h after injury. Subjects were 21 male and six female athletes from a variety of sports who sustained a cerebral concussion between 1997 and 2003. After injury, athletes displayed normal postural stability equivalent to preseason levels. For comparison, COP data also were collected from 15 male and 15 female healthy non-athletes on two occasions. ApEn values were calculated for COP anterior-posterior (AP) and medial-lateral (ML) time series.

Results:Compared to healthy subjects, COP oscillations among athletes generally became more regular (lower ApEn value) after injury despite the absence of postural instability. For AP time series, declines in ApEn values were much larger in SOT conditions 1 and 2 (approximately three times as large as the standard error of the mean) than for all other conditions. For ML time series, ApEn values declined after injury in all sensory conditions (F1,55 = 6.36, p = 0.02).

Conclusions:Athletes who demonstrated normal postural stability after concussion nonetheless displayed subtle changes in postural control. Changes in ApEn may have represented a clinically abnormal finding. ApEn analysis of COP oscillations may be a valuable supplement to existing concussion assessment protocols for athletes.
Changes in joint position sense after surgically treated chronic lateral ankle instability
Authors: Halasi T , Kynsburg Á , Tállay A , Berkes I
Published: October 2005

Background:A search of the literature shows that the effect of surgery on ankle proprioception has been hardly investigated.

Objective:To examine the effect of anatomical reconstruction of the anterolateral capsuloligamentous complex on ankle joint position sense.

Methods:A prospective study using the “slope box” test.Ten consecutive patients were included in the study, and 10 healthy athletes represented the control group.

Results:Similar test-retest reliability rates (overall reliability 0.92; p  =  0.0013) were obtained to those of the original designers of the method. There were no significant differences with respect to side dominance (p  =  0.9216). Investigation of the characteristics of mean absolute estimate errors showed that the controls tested became error prone in the range of slope altitudes 7.5–25° in every direction, compared with the range 0–5° (range of p values 0.00003–0.00072). The results of the intervention group showed that, for the two main directions of interest (anterior and lateral), preoperative differences in mean absolute estimate errors between injured (anterior 3.91 (2.81)°; lateral 4.06 (2.85)°) and healthy (anterior 2.94 (2.21)°, lateral 3.19 (2.64)°) sides (anterior, p  =  0.0124; lateral, p  =  0.0250) had disappeared (postoperative differences: anterior, p  =  0.6906; lateral, p  =  0.4491). The afflicted ankle had improved significantly after surgery in both important directions (anterior, p<0.0001; lateral, p  =  0.0023).

Conclusions:The study shows that differences in joint position sense between healthy and injured ankles disappeared as the result of surgery. Preoperative data show that proprioceptive malfunction is a cause of functional instability. If treatment is by means of surgery, the retensioning of the original anterolateral structures is inevitable, even if other grafting or surgical techniques are used.
Can exercise improve self esteem in children and young people? A systematic review of randomised controlled trials
Authors: Ekeland E , Heian F , Hagen K B
Published: October 2005

A systematic review to determine if exercise alone or as part of a comprehensive intervention can improve self esteem in children and young people is described.

Twenty three randomised controlled trials were analysed. A synthesis of several small, low quality trials indicates that exercise may have short term beneficial effects on self esteem in children and adolescents. However, high quality research on defined populations with adequate follow up is needed.
Partial rupture of the proximal Achilles tendon: a differential diagnostic problem in ultrasound imaging
Authors: Kayser R , Mahlfeld K , Heyde C E
Published: October 2005

Objectives:The aim of this study was to determine whether ultrasound can correctly visualise partial ruptures of the proximal Achilles tendon.

Method:This was a prospective study in which all chronic Achilles tendon injury patients seen at three centres in Germany from 1998 to 2003 were screened. All patients with clinical and/or sonographic signs of abnormalities in the region of the proximal third of the Achilles tendon and tendomuscular junction were included in the analysis. Each of these cases was evaluated by ultrasound following an assessment protocol. Patients with ambiguous ultrasound findings and/or clinical signs were additionally assessed by magnetic resonance imaging (MRI).

Results:Sonomorphologic changes suggestive of an abnormality in the proximal third of the Achilles tendon were detected in 13 out of 320 patients (4.2%) with recurring Achilles tendon complaints. Thirteen patients had clinical signs but no sonographic changes in the tendon. The sonographic diagnosis was correct in 19 cases. In six of the 26 cases studied, MRI was needed to establish the correct diagnosis of partial intratendinous rupture of the proximal Achilles tendon. Sensitivity was 0.5, specificity was 0.81, and the overall agreement of the ultrasound examination was 61.5%. All patients were asymptomatic at follow up at a mean of 14 months (range 12–17 months) after surgery.

Conclusions:Ultrasound is a useful tool for evaluation of proximal Achilles tendon complaints. However, ultrasound is not sufficiently reliable for diagnosis of all pathologies, especially partial ruptures of the Achilles tendon. Thus, the definitive diagnosis must be established by MRI.
Cobalt chloride administration in athletes: a new perspective in blood doping?
Authors: Lippi G , Franchini M , Guidi G C
Published: October 2005

Blood doping is an illegal and unfair way of enhancing athletic performance by increasing the oxygen carrying capacity of the blood. Currently used methods usually involve stimulation of erythropoiesis. Gene therapy targeting the hypoxia inducible factor pathway may be an attractive alternative to traditional blood doping techniques. Hypoxia activates a large number of genes with essential roles in cell and tissue adaptation to low oxygen. Cobalt chloride is a well established chemical inducer of hypoxia-like responses such as erythropoiesis. Cobalt supplementation is not banned and therefore would not be detected by current anti-doping testing. Although there is as yet no direct or anecdotal evidence of cobalt chloride administration to athletes, its use should be warned against as being not only unfair but potentially dangerous.
Acute whole body vibration training increases vertical jump and flexibility performance in elite female field hockey players
Authors: Cochrane D J , Stannard S R
Published: October 2005

Objective:To quantify the acute effect of whole body vibration (WBV) training on arm countermovement vertical jump (ACMVJ), grip strength, and flexibility performance.

Methods:Eighteen female elite field hockey players each completed three interventions of WBV, control, and cycling in a balanced random manner. WBV was performed on a Galileo machine (26 Hz) with six different exercises being performed. For the control, the same six exercises were performed at 0 Hz, whilst cycling was performed at 50 W. Each intervention was 5 min in duration with ACMVJ, grip strength, and flexibility measurements being conducted pre and post intervention.

Results:There was a positive interaction effect (intervention×pre-post) of enhanced ACMVJ (p<0.001) and flexibility (p<0.05) parameters following WBV; however no changes were observed after the control and cycling interventions. There was no interaction effect for grip strength following the three interventions.

Conclusions:Acute WBV causes neural potentiation of the stretch reflex loop as shown by the improved ACMVJ and flexibility performance. Additionally, muscle groups less proportionally exposed to vibration do not exhibit physiological changes that potentiate muscular performance.
THEORETICAL ANALYSIS OF A TIME-FREQUENCY-PCNN AUDITORY CORTEX MODEL
Authors: VOLKMER MARKUS
Published: October 2005

A particular pulsed neural model of the auditory cortex, the Time-Frequency Pulse Coupled Neural Network (TF-PCNN), has shown to decompose its stimulus from the cochlea into characteristic pulse-coded time-frequency (TF) stop and pass regions. A derived sum of spectrograms representation with these zero- or one-valued TF weightings has already been applied for the denoising of speech in a previous work. This decomposition is now related to the concept of TF projection filters, which allows to reinterpret the model equations. The functionality imposed by the model equations can so be accessed and justified from a TF signal processing perspective, in addition to its biological motivation from experimentally observed neurophysiological behavior and simulations.
A HIGH-ORDER GRAPH GENERATING SELF–ORGANIZING STRUCTURE
Authors: RIZZO RICCARDO
Published: October 2005

A large class of neural network models have their units organized in a lattice with fixed topology or generate their topology during the learning process. These network models can be used as neighborhood preserving map of the input manifold, but such a structure is difficult to manage since these maps are graphs with a number of nodes that is just one or two orders of magnitude less than the number of input points (i.e., the complexity of the map is comparable with the complexity of the manifold) and some hierarchical algorithms were proposed in order to obtain a high-level abstraction of these structures. In this paper a general structure capable to extract high order information from the graph generated by a large class of self–organizing networks is presented. This algorithm will allow to build a two layers hierarchical structure starting from the results obtained by using the suitable neural network for the distribution of the input data. Moreover the proposed algorithm is also capable to build a topology preserving map if it is trained using a graph that is also a topology preserving map.
ASSESSING PRE-CRISIS FUNDAMENTALS IN SELECTED ASIAN STOCK MARKETS
Authors: LAU EE LENG , TAN G. K. RANDOLPH , RAHMAN SHAHIDUR
Published: October 2005

In the folklore of emerging markets, there is a popular belief that bubbles are inevitable. In this paper, our objective is to estimate a state-space model for rational bubbles in selected Asian economies with the aid of the Kalman Filter. For each economy, we derive a possible picture of the bubble formation process that is implied by the state-space formulation. The estimation is based on the rational valuation formula for stock prices. Our results provide a possible way of defining the presence of rational bubbles in the stock markets of Taiwan, Singapore, Korea, and Malaysia.
AN ANATOMY OF LAGRANGIAN CHAOS IN LOW REYNOLDS NUMBER FLOW BETWEEN TWO ECCENTRIC ROTATING CYLINDERS
Authors: CHOU MO-HONG , WEI HSIU-CHUAN
Published: October 2005

Chaotic motion of fluid particles in low Reynolds number flow between two eccentric cylinders rotating alternately is studied by investigating the tangling between invariant manifolds of the underlying dynamical system. Such tangles are revealed by a numerical method carrying out the global search of periodic points of the associated Poincaré map and the global tracking of stable and unstable manifolds to the hyperbolic points thus found. Along with such an anatomy the breakup of some elliptic orbits as predicted by Poincaré–Birkhoff theorem is clearly shown. It is found that several drastic changes either in the characteristic of ellipticity and hyperbolicity or in the pattern of homoclinic tangles take place when the cylinders' eccentricity is increased towards its maximum. The results are confirmed either by other numerical approaches or by a rigorous shadowing to a certain extent, and are expected to be of use to some geometric understanding about mixing.
ROBUST BURSTING TO THE ORIGIN: HETEROCLINIC CYCLES WITH MAXIMAL SYMMETRY EQUILIBRIA
Authors: HAWKER DAVID , ASHWIN PETER
Published: October 2005

Robust attracting heteroclinic cycles have been found in many models of dynamics with symmetries. In all previous examples, robust heteroclinic cycles appear between a number of symmetry broken equilibria. In this paper we examine the first example where there are robust attracting heteroclinic cycles that include the origin, i.e. a point with maximal symmetry. The example we study is for vector fields on ℝ3 with (ℤ2)3 symmetry. We list all possible generic (codimension one) local and global bifurcations by which this cycle can appear as an attractor; these include a resonance bifurcation from a limit cycle, direct bifurcation from a stable origin and direct bifurcation from other and more familiar robust heteroclinic cycles.
MODULAR ADAPTIVE CONTROL OF CHAOS IN CHUA'S CIRCUIT
Authors: MAGANTI GANESH B. , SINGH SAHJENDRA N.
Published: October 2005

In this paper, a modular adaptive design is developed for the control of chaos in a Chua's circuit. The dynamics of the Chua's circuit are represented in a parametric strict feedback form. For the purpose of design, it is assumed that all the system parameters are unknown, but the sign of certain parameters and lower bounds on their absolute values are known. Then, an adaptive modular backstepping design approach is used to derive the control system for trajectory tracking of a selected output variable (node voltage). Unlike the direct adaptive controllers for the Chua's circuit available in literature, an input-to-state-stabilizing control law is used herein. The control law accomplishes input-to-state-stability with respect to parameter estimation errors and their derivatives as disturbance inputs. The control system includes a passive identifier (an observer and an adaptation law) for the parameter estimation. In the closed-loop system, control of the node voltage is accomplished, and the remaining state variables remain bounded. Simulation results are presented which show that the controller is effective in accomplishing the precise tracking of the reference trajectory and suppression of the chaotic motion.
MODELING BONE RESORPTION IN 2D CT AND 3D μCT IMAGES
Authors: ZAIKIN A. , KURTHS J. , SAPARIN P. , GOWIN W. , PROHASKA S.
Published: October 2005

We study several algorithms to simulate bone mass loss in two-dimensional and three-dimensional computed tomography bone images. The aim is to extrapolate and predict the bone loss, to provide test objects for newly developed structural measures, and to understand the physical mechanisms behind the bone alteration. Our bone model approach differs from those already reported in the literature by two features. First, we work with original bone images, obtained by computed tomography (CT); second, we use structural measures of complexity to evaluate bone resorption and to compare it with the data provided by CT. This gives us the possibility to test algorithms of bone resorption by comparing their results with experimentally found dependencies of structural measures of complexity, as well as to show efficiency of the complexity measures in the analysis of bone models. For two-dimensional images we suggest two algorithms, a threshold algorithm and a virtual slicing algorithm. The threshold algorithm simulates bone resorption on a boundary between bone and marrow, representing an activity of osteoclasts. The virtual slicing algorithm uses a distribution of the bone material between several virtually created slices to achieve statistically correct results, when the bone-marrow transition is not clearly defined. These algorithms have been tested for original CT 10 mm thick vertebral slices and for simulated 10 mm thick slices constructed from ten 1 mm thick slices. For three-dimensional data, we suggest a variation of the threshold algorithm and apply it to bone images. The results of modeling have been compared with CT images using structural measures of complexity in two- and three-dimensions. This comparison has confirmed credibility of a virtual slicing modeling algorithm for two-dimensional data and a threshold algorithm for three-dimensional data.
COLOR MAPS OF THE KAPLAN–YORKE DIMENSION IN OPTICALLY DRIVEN LASERS: MAXIMIZING THE DIMENSION AND ALMOST-HAMILTONIAN CHAOS
Authors: CHLOUVERAKIS KONSTANTINOS E.
Published: October 2005

In this paper we investigate the geometrical complexity of chaotic attractors in optically injected lasers by calculating the Kaplan–Yorke dimension (D KY ) together with the largest Lyapunov exponent (LLE). For the first time to the best of our knowledge, a color map is constructed indicating regions in the parameter space with high and low dimensionality. It is shown that as the injection power K of the master to the slave laser is increased to high values, the dimension of the attractor decreases for all ranges of the frequency detuning ω. The relation between the trace of the Jacobian matrix and the Kaplan–Yorke dimension shows that the optically injected laser is a system capable to span the dimension anywhere between 2 and 3. A qualitative analysis is finally made in order to identify the material parameters of the slave device for this coupled laser system for a result in the maximized possible dimension, leading to the need for a high electron lifetime and a high linewidth enhancement factor that occur at low temperature operation for a solitary slave semiconductor laser.
PARTICLE TUNNELS FROM GARFINKLE–HORNE BLACK HOLE AND HOROWITZ–STROMINGER BLACK HOLE
Authors: FANG HENGZHONG , REN JUN , ZHAO ZHENG
Published: October 2005

When the black hole radiates particles, it losses energy and shrinks, it is the contraction of the horizon that sets the tunnelling barrier. This article extents the work of M. Parikh to GH black hole and HS black hole. Applying WKB approximation, we calculate the rate of Hawking radiation and found that the rate of tunnelling equals precisely the exponent of the difference of the entropy of the black hole before and after emission. We also obtain the result that the energy spectrum of radiation deviates from the exact thermality.
GENERATING FUNCTIONAL FOR THE GRAVITATIONAL FIELD: IMPLEMENTATION OF AN EVOLUTIONARY QUANTUM DYNAMICS
Authors: CERASTI ERIKA , MONTANI GIOVANNI
Published: October 2005

We provide a generating functional for the gravitational field that is associated with the relaxation of the primary constraints by extending to the quantum sector. This requirement of the theory relies on the assumption that a suitable time variable exists, when taking the T-products of the dynamical variables. More precisely, we start from the gravitational field equations written in the Hamiltonian formalism and expressed via Misner-like variables; hence we construct the equation to which the T-products of the dynamical variables obey and transform this paradigm in terms of the generating functional, as taken on the theory phase-space. We show how the relaxation of the primary constraints (which corresponds to the breakdown of the invariance of the quantum theory under the four-diffeomorphisms) is summarized by a free functional taken on the Lagrangian multipliers, accounting for such constraints in the classical theory. The issue of our analysis is equivalent to a Gupta–Bleuler approach on the quantum implementation of all the gravitational constraints; in fact, in the limit of small ℏ, the quantum dynamics is described by a Schrödinger equation as soon as the mean values of the momenta, associated to the lapse function and the shift vector, are not vanishing. Finally we show how, in the classical limit, the evolutionary quantum gravity reduces to General Relativity in the presence of an Eckart fluid, which corresponds to the classical counterpart of the physical clock, introduced in the quantum theory.
CHARGED SPINNING PARTICLES ON CIRCULAR ORBITS IN THE REISSNER–NORDSTRÖM SPACE–TIME
Authors: BINI DONATO , GERALICO ANDREA , DE FELICE FERNANDO
Published: October 2005

The behavior of charged spinning test particles moving along circular orbits in the equatorial plane of the Reissner–Nordström space–time is studied in the framework of the Dixon–Souriau model completed with standard choices of supplementary conditions. The gravitomagnetic "clock effect," i.e. the delay in the arrival times of two oppositely circulating particles as measured by a static observer, is derived and discussed in the cases in which the particles have equal/opposite charge and spin, the latter being directed along the z-axis.
CYCLIC COMPRESSION AND TENSION REGULATE DIFFERENTLY THE METABOLISM OF CHONDROCYTES
Authors: Lee Chun-Yi , Hsu Horng-Chaung , Zhang Xiaoliu , Wang Der-Yean , Luo Zong-Ping
Published: October 2005

Articular cartilage is the primary structure in joints which is responsible for withstanding compressive loading; however, it is possible that cartilage also experiences localized tensile loading under various loading and boundary conditions. To date, little is known as to whether chondrocyte functions are dependent on the loading variation, especially when loading is switched from compression to tension. The purpose of this study is to examine the metabolism of chondrocytes under both compressive and tensile loadings in vitro. Our results suggest that synthesis of both collagen II and aggrecan is regulated differently by compression and tension at the mRNA level. Tensile loading significantly inhibited the mRNA expression of both collagen II and aggrecan. Since poor content of collagen II and proteoglycan has been considered a detrimental factor in the integrity of cartilage matrix, cartilage degradation and the possible formation of osteoarthritis may be the consequence of loading patterns switching from compression to tension.
SHORT- AND LONG-TERM EFFECTS OF THE 9/11 EVENT: THE INTERNATIONAL EVIDENCE
Authors: RICHMAN VINCENT , SANTOS MICHAEL R. , BARKOULAS JOHN T.
Published: October 2005

This paper analyzes the short- and long-term effects of the September 11, 2001 terrorist attacks on a comprehensive sample of stock market indices from 33 industrial and emerging economies. From a finance-theoretic point of view, we employ the international capital asset pricing model (ICAPM) to analyze the incidence of the 9/11 event. Consistent with expectations, we document statistically negative short-term stock market reactions to the 9/11 event for 28 countries. More importantly, we find increases in the level of systematic risk for 10 stock markets which attest to the presence of negative permanent effects emanating for the 9/11 event. However, a great many capital markets (including the US, Canada, Japan, China, Russia, and the largest European economies) did not experience statistically significant increases in systematic risk in the post-9/11 period. The decisiveness of the evidence clearly points in the direction of resilience and flexibility of the world capital markets.
OPTIMAL INVESTMENT DECISIONS FOR A PORTFOLIO WITH A ROLLING HORIZON BOND AND A DISCOUNT BOND
Authors: BIELECKI TOMASZ R. , PLISKA STANLEY , YONG JIONGMIN
Published: October 2005

An optimal investment problem is considered for a continuous-time market consisting of the usual bank account, a rolling horizon bond, and a discount bond whose maturity coincides with the planning horizon. Two economic factors, namely, the short rate and the risk-free yield of some fixed maturity, are modeled as Gaussian processes. For the problem of maximizing expected CRRA utility of terminal wealth, the optimal portfolio is obtained through a Bellman equation. The results are noteworthy because the discount bond, which is the riskless asset for the investor, causes a degeneracy due to its zero volatility at the planning horizon. Indeed, this delicate matter is treated rigorously for what seems to be the first time, and it is shown that there exists an optimal, admissible (but unbounded) trading strategy.
Geochemical mapping: technique or art?
Authors: Reimann Clemens
Published: October 2005

Various techniques for producing geochemical maps are reviewed. Interpretation of processes leading to the observed element distribution will be facilitated when the data structure is displayed in a geochemical map. This can be achieved by using the boxplot or percentiles, evenly spread over the whole data range, for class selection. Map scale (to purpose), type and amount of background map information, choice of symbols (black-and-white mapping) and, for colour maps, the colour scale are important issues that need consideration.
G-BASE: baseline geochemical mapping of Great Britain and Northern Ireland
Authors: Johnson C.C. , Breward N. , Ander E.L. , Ault L.
Published: October 2005

The Geochemical Baseline Survey of the Environment is a long-established, high-resolution regional geochemical mapping project run by the British Geological Survey. A project initially stimulated by mineral exploration and to assist geological mapping has successfully evolved into a survey that has many environmental applications. Much of the current demand for surface geochemical data is driven by legislation. The geochemical mapping, originally based on the collection of drainage samples, has expanded to include soils and a further suite of determinands in stream waters. The methodology of the project and application of the baseline data are described and issues common to worldwide geochemical mapping programmes are discussed.
Increased collagen content in insulin-resistant skeletal muscle
Authors: Berria Rachele , Wang Lishan , Richardson Dawn K. , Finlayson Jean , Belfort Renata , Pratipanawatr Thongchai , De Filippis Elena A. , Kashyap Sangeeta , Mandarino Lawrence J.
Published: October 2005

Oversupply and underutilization of lipid fuels are widely recognized to be strongly associated with insulin resistance in skeletal muscle. Recent attention has focused on the mechanisms underlying this effect, and defects in mitochondrial function have emerged as a potential player in this scheme. Because evidence indicates that lipid oversupply can produce abnormalities in extracellular matrix composition and matrix changes can affect the function of mitochondria, the present study was undertaken to determine whether muscle from insulin-resistant, nondiabetic obese subjects and patients with type 2 diabetes mellitus had increased collagen content. Compared with lean control subjects, obese and type 2 diabetic subjects had reduced muscle glucose uptake ( P < 0.01) and decreased insulin stimulation of tyrosine phosphorylation of insulin receptor substrate-1 and its ability to associate with phosphatidylinositol 3-kinase ( P < 0.01 and P < 0.05). Because it was assayed by total hydroxyproline content, collagen abundance was increased in muscle from not only type 2 diabetic patients but also nondiabetic obese subjects (0.26 ± 0.05, 0.57 ± 0.18, and 0.67 ± 0.20 μg/mg muscle wet wt, lean controls, obese nondiabetics, and type 2 diabetics, respectively), indicating that hyperglycemia itself could not be responsible for this effect. Immunofluorescence staining of muscle biopsies indicated that there was increased abundance of types I and III collagen. We conclude that changes in the composition of the extracellular matrix are a general characteristic of insulin-resistant muscle.
Extravascular pressure modulates responses of isolated rat coronary arteries to vasodilator, but not vasoconstrictor, stimuli
Authors: Azzawi May , Austin Clare
Published: October 2005

The aims of the study were to investigate whether elevated extravascular pressure modulates responses of isolated rat coronary arteries to constrictor and dilator stimuli. Isolated segments of rat coronary artery were mounted in a modified pressure myograph system that allowed independent modulation of both intra- and extravascular pressures. The influence of elevated extravascular pressure on stable levels of myogenic tone and on responses to vasoconstrictor and vasodilator stimuli was investigated at constant overall transmural pressures. Stable levels of myogenic tone were independent of the relative levels of intra- and extravascular pressure, as were responses to depolarization and to addition of the thromboxane agonist U-46619. Elevating extravascular pressure, however, significantly reduced dilatory responses to introduction of intraluminal flow and to addition of endothelium-dependent and endothelium-independent vasodilatory agonists. These results support the notion that elevated extravascular pressure may attenuate responses of coronary arteries to a variety of dilatory stimuli. This finding may be of relevance to cardiac disorders associated with elevated ventricular pressures.
Calcium receptor is functionally expressed in rat neonatal ventricular cardiomyocytes
Authors: Tfelt-Hansen Jacob , Hansen Jakob Lerche , Smajilovic Sanela , Terwilliger Ernest F. , Haunso Stig , Sheikh Soren P.
Published: October 2005

Both intra- and extracellular calcium play multiple roles in the physiology and pathophysiology of cardiomyocytes, especially in stimulus-contraction coupling. The intracellular calcium level is closely controlled through the concerted actions of calcium channels, exchangers, and pumps; however, the expression and function(s) of the so-called calcium-sensing receptor (CaR) in the heart remain less well characterized. The CaR is a seven-transmembrane receptor, which, in response to noncovalent binding of extracellular calcium, activates intracellular effectors, including G proteins and extracellular signal-regulated kinases (ERK1/2). We have shown that cultured neonatal cardiomyocytes express the CaR messenger RNA and the CaR protein. Furthermore, increasing concentrations of extracellular calcium and a type II CaR activator “calcimimetic” caused inositol phosphate (IP) accumulation, downregulated tritiated thymidine incorporation, and supported ERK1/2 phosphorylation, suggesting that the CaR protein is functionally active. Interestingly, the calcimimetic induced a more rapid ERK1/2 phosphorylation than calcium and left-shifted the IP concentration-response curve for extracellular calcium, supporting the hypothesis that CaR is functionally expressed in cardiac myocytes. This notion was underscored by studies using a virus containing a dominant-negative CaR construct, because this protein blunted the calcium-induced IP response. In conclusion, we have shown that the CaR is functionally expressed in neonatal ventricular cardiomyocytes and that the receptor activates second messenger pathways, including IP and ERK, and decreases DNA synthesis. A specific calcium-sensing receptor on cardiac myocytes could play a role in regulating cardiac development, function, and homeostasis.
Influence of pulmonary arterial endothelial cells on quinone redox status: effect of hyperoxia-induced NAD(P)H:quinone oxidoreductase 1
Authors: Merker Marilyn P. , Audi Said H. , Bongard Robert D. , Lindemer Brian J. , Krenz Gary S.
Published: October 2005

The objective of this study was to examine the impact of chronic hyperoxic exposure (95% O2for 48 h) on intact bovine pulmonary arterial endothelial cell redox metabolism of 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ). DQ or durohydroquinone (DQH2) was added to normoxic or hyperoxia-exposed cells in air-saturated medium, and the medium DQ concentrations were measured over 30 min. DQ disappeared from the medium when DQ was added and appeared in the medium when DQH2was added, such that after ∼15 min, a steady-state DQ concentration was approached that was ∼4.5 times lower for the hyperoxia-exposed than the normoxic cells. The rate of DQ-mediated reduction of the cell membrane-impermeant redox indicator, potassium ferricyanide [Fe(CN)[Formula: see text]], was also approximately twofold faster for the hyperoxia-exposed cells. Inhibitor studies and mathematical modeling suggested that in both normoxic and hyperoxia-exposed cells, NAD(P)H:quinone oxidoreductase 1 (NQO1) was the dominant DQ reductase and mitochondrial electron transport complex III the dominant DQH2oxidase involved and that the difference between the net effects of the cells on DQ redox status could be attributed primarily to a twofold increase in the maximum NQO1-mediated DQ reduction rate in the hyperoxia-exposed cells. Accordingly, NQO1 protein and total activity were higher in hyperoxia-exposed than normoxic cell cytosolic fractions. One outcome for hyperoxia-exposed cells was enhanced protection from cell-mediated DQ redox cycling. This study demonstrates that exposure to chronic hyperoxia increases the capacity of pulmonary arterial endothelial cells to reduce DQ to DQH2via a hyperoxia-induced increase in NQO1 protein and total activity.
Endothelin antagonism prevents early EGFR transactivation but not increased matrix metalloproteinase activity in diabetes
Authors: Portik-Dobos Vera , Harris Alex K. , Song Weiwei , Hutchinson Jimmie , Johnson Maribeth H. , Imig John D. , Pollock David M. , Ergul Adviye
Published: October 2005

Although past studies have demonstrated decreased renal matrix metalloproteinase (MMP) activity in type 1 diabetes and in mesangial cells grown under high glucose conditions, renal MMP expression and activity in type 2 diabetes and the regulation of MMPs by profibrotic factors involved in diabetic renal complications such as endothelin-1 (ET-1) remained unknown. The renal expression and activity of MMPs in type 2 diabetic Goto-Kakizaki (GK) rats treated with vehicle or ETAreceptor selective antagonist ABT-627 for 4 wk were assessed by gelatin zymography, fluorogenic gelatinase assay, and immunoblotting. In addition, expression and phosphorylation of epidermal growth factor receptor (EGFR) and connective tissue growth factor were evaluated by immunoblotting. Renal sections stained with Masson trichrome were used to investigate kidney structure. MMP-2 activity and protein levels were significantly increased in both cortical and medullary regions in the GK rats. Membrane-bound MMP (MT1-MMP), MMP-9, and fibronectin levels were also increased, and ABT-627 treatment did not have an effect on MMP activity and expression. Histological analysis of kidneys did not reveal any structural changes. Phosphorylation of EGFR was significantly increased in the diabetic animals, and ABT-627 treatment prevented this increase, suggesting ET-1-mediated transactivation of EGFR. These results suggest that there is early upregulation of renal MMPs in the absence of any kidney damage. Although the ETAreceptor subtype is not involved in the early activation of MMPs in type 2 diabetes, ET-1 contributes to transactivation of growth-promoting and profibrotic EGFR.
Lessons from an estivating frog: sparing muscle protein despite starvation and disuse
Authors: Hudson Nicholas J. , Lehnert Sigrid A. , Ingham Aaron B. , Symonds Beth , Franklin Craig E. , Harper Gregory S.
Published: October 2005

Long (6- to 9-mo) bouts of estivation in green-striped burrowing frogs lead to 28% atrophy of cruralis oxidative fibers ( P < 0.05) and some impairment of in vitro gastrocnemius endurance ( P < 0.05) but no significant deficit in maximal twitch force production. These data suggest the preferential atrophy of oxidative fibers at a rate slower than, but comparable to, laboratory disuse models. We tested the hypothesis that the frog limits atrophy by modulating oxidative stress. We assayed various proteins at the transcript level and verified these results for antioxidant enzymes at the biochemical level. Transcript data for NADH ubiquinone oxidoreductase subunit 1 (71% downregulated, P < 0.05) and ATP synthase (67% downregulated, P < 0.05) are consistent with mitochondrial quiescence and reduced oxidant production. Meanwhile, uncoupling protein type 2 transcription ( P = 0.31), which is thought to reduce mitochondrial leakage of reactive oxygen species, was maintained. Total antioxidant defense of water-soluble (22.3 ± 1.7 and 23.8 ± 1.5 μM/μg total protein in control and estivator, respectively, P = 0.53) and membrane-bound proteins (31.5 ± 1.9 and 42.1 ± 7.3 μM/μg total protein in control and estivator, respectively, P = 0.18) was maintained, equivalent to a bolstering of defense relative to oxygen insult. This probably decelerates muscle atrophy by preventing accumulation of oxidative damage in static protein reserves. Transcripts of the mitochondrially encoded antioxidant superoxide dismutase type 2 (67% downregulated, P < 0.05) paralleled mitochondrial activity, whereas nuclear-encoded catalase and glutathione peroxidase were maintained at control values ( P = 0.42 and P = 0.231), suggesting a dissonance between mitochondrial and nuclear antioxidant expression. Pyruvate dehydrogenase kinase 4 transcription was fourfold lower in estivators ( P = 0.11), implying that, in contrast to mammalian hibernators, this enzyme does not drive the combustion of lipids that helps spare hypometabolic muscle.
Osmolarity-induced renin secretion from kidneys: evidence for readily releasable renin pools
Authors: Kurtz Armin , Schweda Frank
Published: October 2005

Our study aimed to characterize the influence of changes in extracellular osmolarity on renin secretion from the whole kidney. For this purpose, the osmolarity of the perfusion medium of isolated rat or mouse kidneys was either decreased by lowering the NaCl concentration by 20% or was increased up to 133% by the addition of various salts or sugars. It turned out that changes in osmolarity led to instantaneous transient changes followed by a plateau of renin secretion, in that increases in osmolarity stimulated renin secretion, whereas decreases attenuated renin secretion. The peak amplitude of changes in renin secretion was related to steady-state renin secretion rates before the osmotic challenge but was independent of the maneuver used to modulate steady-state renin secretion. Osmolarity-induced changes in renin secretion were more related to relative rather than to absolute changes in osmolarity and were not dependent on the formation of nitric oxide or of prostanoids and did not require Na-K-2Cl cotransport function or swelling-activated chloride channels. Moreover, we obtained evidence that the pool of renin secretion excitable by hyperosmolarity is exhaustible and that its complete refilling takes at least 2 min. The observed behavior of renin secretion fits the concept about exocytosis proposing the existence of different pools of committed secretory vesicles, which have not yet undergone the final modification for initiation of exocytosis. Probably, a pool of readily releasable vesicles determines steady-state secretion rates from kidneys.
Longitudinal study of urinary excretion of phosphate, calcium, and uric acid in mutant NHERF-1 null mice
Authors: Weinman Edward J. , Mohanlal Viresh , Stoycheff Nicholas , Wang Fengying , Steplock Deborah , Shenolikar Shirish , Cunningham Rochelle
Published: October 2005

NHERF-1 binds numerous renal protein targets, including the proximal tubule transporters Na+/H+ exchanger 3 (NHE3) and Na+-phosphate cotransporter 2a (Npt2a). Young NHERF-1−/− male mice display defective targeting of Npt2a to apical membranes in the renal proximal tubule and manifest hypophosphatemia and increased urinary excretion of phosphate. The present studies describe the changes in the urinary excretion of phosphate, calcium, uric acid, and sodium in male and female wild-type and NHERF-1 null mice over a time period from 12 to 54 wk of age. Young male and female NHERF-1−/− mice demonstrated increased urinary excretion of phosphate and urine phosphate/creatinine ratios. There was an age-related decline in the phosphate/creatinine ratio in mutant mice such that there were no differences between wild-type and NHERF-1−/− by 24 to 30 wk of age despite the continued presence of hypophosphatemia. Male and female NHERF-1 null mice also demonstrate increased urine calcium/creatinine and uric acid/creatinine ratios compared with wild-type controls. These studies indicate defects in the renal tubule transport of phosphate, calcium, and uric acid in NHERF-1−/− male and female mice that could account for the increased deposition of calcium in the papilla of null mice.
Exaggerated airway narrowing in mice treated with intratracheal cationic protein
Authors: Bates Jason H. T. , Wagers Scott S. , Norton Ryan J. , Rinaldi Lisa M. , Irvin Charles G.
Published: October 2005

Airway hyperresponsiveness in mice with allergic airway inflammation can be attributed entirely to exaggerated closure of peripheral airways (Wagers S, Lundblad LK, Ekman M, Irvin CG, and Bates JHT. J Appl Physiol 96: 2019–2027, 2004). However, clinical asthma can be characterized by hyperresponsiveness of the central airways as well as the lung periphery. We, therefore, sought to establish a complementary model of hyperresponsiveness in the mouse due to excessive narrowing of the airways. We treated mice with a tracheal instillation of the cationic protein poly-l-lysine (PLL), hypothesizing that this would reduce the barrier function of the epithelium and thereby render the underlying airway smooth muscle more accessible to aerosolized methacholine. The PLL-treated animals were hypersensitive to methacholine: they exhibited an exaggerated response to submaximal doses but had a maximal response that was similar to controls. With the aid of a computational model of the mouse lung, we conclude that the methacholine responsiveness of PLL-treated mice is fundamentally different in nature to the hyperresponsiveness that we found previously in mice with allergically inflamed lungs.
Microarray screening of suppression subtractive hybridization-PCR cDNA libraries identifies novel RNAs regulated by dehydration in the rat supraoptic nucleus
Authors: Ghorbel Mohamed T. , Sharman Greig , Hindmarch Charles , Becker Kevin G. , Barrett Tanya , Murphy David
Published: October 2005

The magnocellular neurons (MCNs) of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus are the principal site of biosynthesis of prepropeptide precursor of the antidiuretic hormone vasopressin (VP). This precursor is processed during anterograde axonal transportation to terminals in the posterior pituitary gland, where biologically active VP is stored until release into the general circulation in response to physiological activation of the SON by osmotic cues. By binding to V2-type receptors located in the kidney, VP decreases the amount of water lost in urine. Osmotic activation of the SON is accompanied by a dramatic morphological and functional remodeling. We have sought to understand the mechanistic basis of this plasticity in terms of the differential expression of genes. To identify such genes, we adopted an unbiased global approach based on suppressive subtractive hybridization-polymerase chain reaction (SSH-PCR) Using this method, we generated libraries of clones putatively differentially expressed in control vs. dehydrated SON. To rapidly screen these libraries, 1,152 clones were subjected to microarray analysis, resulting in the identification of 459 differentially expressed transcripts. cDNA clones corresponding to 56 of these RNAs were sequenced, revealing many of them to be novel expressed sequence tags (ESTs). Four transcripts were shown by in situ hybridization (ISH) to be significantly up- or downregulated in the SON after dehydration. These genes may represent novel effectors or mediators of SON physiological remodeling.
Lipoprotein-Associated Phospholipase A
2
Is an Independent Marker for Coronary Endothelial Dysfunction in Humans
Authors: Yang Eric H. , McConnell Joseph P. , Lennon Ryan J. , Barsness Gregory W. , Pumper Geralyn , Hartman Stacy J. , Rihal Charanjit S. , Lerman Lilach O. , Lerman Amir
Published: October 2005

Objective—

The purpose of the current study was to determine whether lipoprotein-associated phospholipase A
2
(Lp-PLA
2
) is associated with coronary endothelial dysfunction and is a predictor of endothelial dysfunction in humans.

Methods and Results—

Patients (172) with no significant coronary artery disease (<30% stenosis) undergoing assessment of coronary endothelial function were studied. Endothelial function was assessed by the change in coronary blood flow and coronary artery diameter in response to intracoronary acetylcholine. Plasma concentrations of Lp-PLA
2
were measured, and patients were divided into tertiles. Patients in tertiles 2 and 3 had a significantly lower change in coronary blood flow (63.8±73.2 and 32.0±71.7 versus 78.4±73.2%;
P
<0.001) and greater epicardial coronary artery vasoconstriction (−14.1±14.7 and −23.3±25.1 versus −9.5±15.2% mean diameter change;
P
<0.001) in response to acetylcholine. Patients with coronary endothelial dysfunction had significantly higher serum concentrations of Lp-PLA
2
than those with normal endothelial function (246.2±71.6 versus 209±56.7 ng/mL;
P
=0.001). The odds ratio for coronary endothelial dysfunction in patients with Lp-PLA
2
in the highest tertile was 3.3 (95% CI, 1.6 to 6.6).

Conclusions—

Lp-PLA
2
is independently associated with coronary artery endothelial dysfunction and is a strong predictor of endothelial dysfunction in humans.
Obesity, Peroxisome Proliferator-Activated Receptor, and Atherosclerosis in Type 2 Diabetes
Authors: Blaschke Florian , Takata Yasunori , Caglayan Evren , Law Ronald E. , Hsueh Willa A.
Published: October 2005

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. The 3 PPAR isotypes, PPAR-α, PPAR-γ, and PPAR-δ, play a key role in the regulation of lipid and glucose metabolism. Obesity and the interrelated disorders of the metabolic syndrome have become a major worldwide health problem. In this review, we summarize the critical role of PPARs in regulating inflammation, lipoprotein metabolism, and glucose homeostasis and their potential implications for the treatment of obesity, diabetes, and atherosclerosis.
Embryonic
even skipped
–Dependent Muscle and Heart Cell Fates Are Required for Normal Adult Activity, Heart Function, and Lifespan
Authors: Fujioka Miki , Wessells Robert J. , Han Zhe , Liu Jiandong , Fitzgerald Kerry , Yusibova Galina L. , Zamora Monica , Ruiz-Lozano Pilar , Bodmer Rolf , Jaynes James B.
Published: October 2005

The
Drosophila
pair-rule gene
even skipped
(
eve
) is required for embryonic segmentation and later in specific cell lineages in both the nervous system and the mesoderm. We previously generated
eve
mesoderm-specific mutants by combining an
eve
null mutant with a rescuing transgene that includes the entire locus, but with the mesodermal enhancer removed. This allowed us to analyze in detail the defects that result from a precisely targeted elimination of mesodermal
eve
expression in the context of an otherwise normal embryo. Absence of mesodermal
eve
causes a highly selective loss of the entire
eve
-expressing lineage in this germ layer, including those progeny that do not continue to express
eve
, suggesting that mesodermal
eve
precursor specification is not implemented. Despite the resulting absence of a subset of muscles and pericardial cells, mesoderm-specific
eve
mutants survive to fertile adulthood, providing an opportunity to examine the effects of these developmental abnormalities on adult fitness and heart function. We find that in these mutants, flying ability, myocardial performance under normal and stressed conditions, and lifespan are severely reduced. These data imply a nonautonomous role of the affected pericardial cells and body wall muscles in developing and/or maintaining cardiac performance and possibly other functions contributing to normal lifespan. Given the similarities of molecular-genetic control between
Drosophila
and vertebrates, these findings suggest that peri/epicardial influences may well be important for proper myocardial function.