bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of caveolin‐3 induced by the dystrophy‐associated P104L mutation impairs L‐type calcium channel function in mouse skeletal muscle cells
Authors: Couchoux Harold , Allard Bruno , Legrand Claude , Jacquemond Vincent , Berthier Christine
Published: February 2007

Caveolins are membrane scaffolding proteins that associate with and regulate a variety of signalling proteins, including ion channels. A deficiency in caveolin‐3 (Cav‐3), the major striated muscle isoform, is responsible for skeletal muscle disorders, such as limb‐girdle muscular dystrophy 1C (LGMD 1C). The molecular mechanisms leading to the muscle wasting that characterizes this pathology are poorly understood. Here we show that a loss of Cav‐3 induced by the expression of the LGMD 1C‐associated mutant P104L (Cav‐3P104L) provokes a reduction by half of the maximal conductance of the voltage‐dependent L‐type Ca2+ channel in mouse primary cultured myotubes and fetal skeletal muscle fibres. Confocal immunomiscrocopy indicated a colocalization of Cav‐3 and Cav1.1, the pore‐forming subunit of the L‐type Ca2+ channel, at the surface membrane and in the developing T‐tubule network in control myotubes and fetal fibres. In myotubes expressing Cav‐3P104L, the loss of Cav‐3 was accompanied by a 66% reduction in Cav1.1 mean labelling intensity. Our results suggest that Cav‐3 is involved in L‐type Ca2+ channel membrane function and localization in skeletal muscle cells and that an alteration of L‐type Ca2+ channels could be involved in the physiopathological mechanisms of caveolinopathies.
Dendritic D‐type potassium currents inhibit the spike afterdepolarization in rat hippocampal CA1 pyramidal neurons
Authors: Metz Alexia E. , Spruston Nelson , Martina Marco
Published: February 2007

In CA1 pyramidal neurons, burst firing is correlated with hippocampally dependent behaviours and modulation of synaptic strength. One of the mechanisms underlying burst firing in these cells is the afterdepolarization (ADP) that follows each action potential. Previous work has shown that the ADP results from the interaction of several depolarizing and hyperpolarizing conductances located in the soma and the dendrites. By using patch‐clamp recordings from acute rat hippocampal slices we show that D‐type potassium current modulates the size of the ADP and the bursting of CA1 pyramidal neurons. Sensitivity to α‐dendrotoxin suggests that Kv1‐containing potassium channels mediate this current. Dual somato‐dendritic recording, outside‐out dendritic recordings, and focal application of dendrotoxin together indicate that the channels mediating this current are located in the apical dendrites. Thus, our data present evidence for a dendritic segregation of Kv1‐like channels in CA1 pyramidal neurons and identify a novel action for these channels, showing that they inhibit action potential bursting by restricting the size of the ADP.
Objective Function Effect Based Pattern Search—An Implementation for 3D Component Layout
Authors: Aladahalli Chandankumar , Cagan Jonathan , Shimada Kenji
Published: February 2007

Generalized pattern search (GPS) algorithms have been used successfully to solve three-dimensional (3D) component layout problems. These algorithms use a set of patterns and successively decreasing step sizes of these patterns to explore the search space before converging to good local minima. A shortcoming of conventional GPS algorithms is the lack of recognition of the fact that patterns affect the objective function by different amounts and hence it might be efficient to introduce them into the search in a certain order rather than introduce all of them at the beginning of the search. To address this shortcoming, it has been shown by the authors in previous work that it is more efficient to schedule patterns in decreasing order of their effect on the objective function. The effect of the patterns on the objective function was estimated by the a priori expectation of the objective function change due to the patterns. However, computing the a priori expectation is expensive, and to practically implement the scheduling of patterns, an inexpensive estimate of the effect on the objective function is necessary. This paper introduces a metric for geometric layout called the sensitivity metric that is computationally inexpensive, to estimate the effect of pattern moves on the objective function. A new pattern search algorithm that uses the sensitivity metric to schedule patterns is shown to perform as well as the pattern search algorithm that used the a priori expectation of the objective function change. Though the sensitivity metric applies to the class of geometric layout or placement problems, the foundation and approach is useful for developing metrics for other optimization problems.
Model-based Rapid Redesign Using Decomposition Patterns
Authors: Chen Li , Macwan Ashish , Li Simon
Published: February 2007

This paper presents a pattern-based decomposition methodology for rapid redesign to support design customization in agile manufacturing of evolutionary products. The methodology has three functional phases. The first phase, called design dependency analysis, systematizes and reorganizes the intrinsic coupling structure of a given existing design model that is represented using the design dependency matrix. The second phase, called redesign partitioning analysis, generates alternative redesign pattern solutions to form a solution selection space through a three-stage procedure. The third phase, called pattern selection analysis, finds an optimal redesign pattern solution that entails the least potential redesign effort (in the subsequent solution process). Each pattern solution identifies and delimits the portions of the design model that need to be recomputed, thus expediting the redesign solution process. In such a way, one can treat the recomputation of the entire model, which is a conventional and computation-expensive solution approach, only as the last resort to solve the redesign problem given. An example redesign problem is used for the methodology illustration.
Static Balancing of Tensegrity Mechanisms
Authors: Arsenault Marc , Gosselin Clément M.
Published: February 2007

The computation of the equilibrium configurations of tensegrity mechanisms is often a very tedious task even for relatively simple architectures. However, it has been observed that the complexity of this problem is significantly reduced when gravitational loads are compensated with the use of static balancing techniques. In this work, the general static balancing conditions are adapted for the case of tensegrity mechanisms. Afterward, the modified conditions are applied to two new spatial three-degree-of-freedom tensegrity mechanisms.
Residue Level Inverse Kinematics of Peptide Chains in the Presence of Observation Inaccuracies and Bond Length Changes
Authors: Subramanian Raghavendran , Kazerounian Kazem
Published: February 2007

The process of calculating the dihedral angles of a peptide chain from atom coordinates in the chain is called residue level inverse kinematics. The uncertainties and experimental observation inaccuracies in the atoms’ coordinates handicap this otherwise simple and straightforward process. In this paper, we present and analyze three new efficient methodologies to find all the dihedral angles of a peptide chain for a given conformation. Comparison of these results with the dihedral angle values reported in the protein data bank (PDB) indicates significant improvements. While these improvements benefit most modeling methods in protein analysis, it is in particular, very significant in homology modeling where the dihedral angles are the generalized coordinates (structural variables). The first method presented here fits a best plane through five atoms of each peptide unit. The angle between the successive planes is defined as the dihedral angle. The second method is based on the zero-position analysis method. Successive links in this method rotate by the dihedral angles so as to minimize the structural error between respective atoms in the model conformation with given atoms’ coordinates. Dihedral angle final values correspond to the minimum structural error configuration. In this method, singular value decomposition technique is used to best fit the atoms in the two conformations. The third method is a variant of the second method. In this instead of rotating all the links successively only three links are matched each time to extract the dihedral angle of the middle link. By doing so, the error accumulation on the successive links is reduced. This paper focuses on the Euclidean norm as the measure of merit (structural error) to compare different methods with the PDB. This Euclidean norm is further, minimized by optimizing the geometrical features of the peptide plane.
Target Tracking Manipulation Theories for Combined Force and Position Control in Open and Closed Loop Manipulators
Authors: Giblin David J. , Zongliang Mu , Kazerounian Kazem , Gan ZhongXue
Published: February 2007

This paper presents a new manipulation theory for controlling compliant motions of a robotic manipulator. In previous closed loop control methods, both direct kinematics and inverse kinematics of a manipulator must be resolved to convert feedback force and position data from Cartesian space to joint space. However, in many cases, the solution of direct kinematics in a parallel manipulator or the solution of inverse kinematics in a serial manipulator is not easily available. In this study, the force and position data are packed into one set of “motion feedback,” by replacing the force errors with virtual motion quantities, or one set of “force feedback,” by replacing motion errors with virtual force quantities. The joint torques are adjusted based on this combined feedback package. Since only Jacobian of direct kinematics or Jacobian of inverse kinematics is used, the computational complexity is reduced significantly, and the control scheme is more stable at or near singular manipulator configurations. Furthermore, the complexities and oddities associated with hybrid control, such as nonuniformity of the space matrix and incompatibility of simultaneous position and force control in the same direction are circumvented. The applications of this theory are demonstrated in simulation experiments with both serial and parallel manipulators.
Design of a Universal Software System for Controlling Geometric Measuring Devices
Authors: Lübke K. , Pieper C. , Goch G. , Kammers K.
Published: February 2007

The research project UP-Prosa, a German acronym for universal and unified platform for planning, programming, controlling and evaluating processes, of measuring, aims at realizing a platform to design and control processes of geometry measurements, which supports a broad variety of measuring devices via one user interface. Based on Windows Operating System (OS) a software was developed able to control inspection devices for different types of geometry measurements (coordinate measuring machine, form, roughness, gear) and manufacturers by one defined communication protocol. This uniform user interface contains the programming of measurement processes, evaluation algorithms with standardized methods, as well as abilities to generate record pages at the users expectations. At the level of geometric measuring devices a universal controlling software called Prosa InterCommunicator (Prosa-ICom) was designed. Prosa-ICom communicates via network with the user interface and translates the defined protocol into a measuring device specific form. The internal structure is extendable and so it seems to be appropriate for both new developments and upgrades (retrofit) for all kinds of geometric measuring devices.
Establishing Conformity to Tolerances by Coordinate Measuring Machines: A First Step for a Statistical Approach
Authors: Barbato Giulio , D’Agostino Daniela , Levi Raffaello
Published: February 2007

Conformity to tolerances is currently assessed taking into account the maximum material condition. Coordinate measuring machines do not however operate accordingly, a small sample only of points on workpiece surface being actually contacted, with a fairly low chance of hitting the outmost point. That problem should therefore be properly addressed using statistical methods, as currently considered also by the ISO Technical Committee on “Geometrical Product Specifications and Verification.” This paper proposes to associate maximum material with the statistical distribution of maximum; typical examples of saw-tooth and round grooved surface profiles are theoretically examined. An actual surface with a good finish, representing the common case of normal distribution, was experimentally evaluated, showing that the method proposed produces consistent results. Furthermore, the method proposed readily associates results obtained with a statistical confidence interval; the uncertainty of results obtained can thus be assessed at any given confidence level.
Focusing Beyond the Diffraction Limit with Far-Field Time Reversal
Authors: Lerosey Geoffroy , de Rosny Julien , Tourin Arnaud , Fink Mathias
Published: February 2007

We present an approach for subwavelength focusing of microwaves using both a time-reversal mirror placed in the far field and a random distribution of scatterers placed in the near field of the focusing point. The far-field time-reversal mirror is used to build the time-reversed wave field, which interacts with the random medium to regenerate not only the propagating waves but also the evanescent waves required to refocus below the diffraction limit. Focal spots as small as one-thirtieth of a wavelength are described. We present one example of an application to telecommunications, which shows enhancement of the information transmission rate by a factor of 3.
Redirection of Silencing Targets by Adenosine-to-Inosine Editing of miRNAs
Authors: Kawahara Yukio , Zinshteyn Boris , Sethupathy Praveen , Iizasa Hisashi , Hatzigeorgiou Artemis G. , Nishikura Kazuko
Published: February 2007

Primary transcripts of certain microRNA (miRNA) genes are subject to RNA editing that converts adenosine to inosine. However, the importance of miRNA editing remains largely undetermined. Here we report that tissue-specific adenosine-to-inosine editing of miR-376 cluster transcripts leads to predominant expression of edited miR-376 isoform RNAs. One highly edited site is positioned in the middle of the 5′-proximal half “seed” region critical for the hybridization of miRNAs to targets. We provide evidence that the edited miR-376 RNA silences specifically a different set of genes. Repression of phosphoribosyl pyrophosphate synthetase 1, a target of the edited miR-376 RNA and an enzyme involved in the uric-acid synthesis pathway, contributes to tight and tissue-specific regulation of uric-acid levels, revealing a previously unknown role for RNA editing in miRNA-mediated gene silencing.
GLUING BIFURCATIONS IN CHUA OSCILLATOR
Authors: ROY PRODYOT KUMAR , DANA SYAMAL KUMAR
Published: February 2007

Gluing bifurcation in a modified Chua's oscillator is reported. Keeping other parameters fixed when a control parameter is varied in the modified oscillator model, two symmetric homoclinic orbits to saddle focus at origin, which are mirror images of each other, are glued together for a particular value of the control parameter. In experiments, two asymmetric limit cycles are homoclinic to the saddle focus origin for different values of the control parameter. However, imperfect gluing bifurcation has been observed, in experiments, when one stable and unstable limit cycles merge to the saddle focus origin via saddle-node bifurcation.
A STRANGE ATTRACTOR WITH LARGE ENTROPY IN THE UNFOLDING OF A LOW RESONANT DEGENERATE HOMOCLINIC ORBIT
Authors: MARTENS M. , NAUDOT V. , YANG J.
Published: February 2007

The unfolding of a vector field exhibiting a degenerate homoclinic orbit of inclination-flip type is studied. The linear part of the unperturbed system possesses a resonance but the coefficient of the corresponding monomial vanishes. We show that for an open set in the parameter space, the system possesses a suspended cubic Hénon-like map. As a consequence, strange attractors with entropy close to log 3 persist in a positive Lebesgue measure set.
DYNAMICS OF A HARMONICALLY EXCITED OSCILLATOR WITH DRY-FRICTION ON A SINUSOIDALLY TIME-VARYING, TRAVELING SURFACE
Authors: LUO ALBERT C. J. , GEGG BRANDON C.
Published: February 2007

In this paper, periodic motion in an oscillator moving on the periodically traveling belts with dry friction is investigated. The conditions of stick and nonstick motions for such an oscillator are obtained in the relative motion frame, and the grazing and stick (or sliding) bifurcations are presented as well. The periodic motions of such an oscillator are predicted analytically and numerically, and the analytical prediction is based on the appropriate mapping structures. The local stability and bifurcation for such periodic motions are obtained. The periodic motions are illustrated through the displacement, velocity and force responses in absolute and relative frames. This investigation provides an efficient method to predict periodic motions of such an oscillator involving dry-friction. The significance of this investigation lies in controlling motion of such friction-induced oscillator in industry.
BUILDING ELECTRONIC BURSTERS WITH THE MORRIS–LECAR NEURON MODEL
Authors: WAGEMAKERS ALEXANDRE , SANJUÁN MIGUEL A. F. , CASADO JOSÉ M. , AIHARA KAZUYUKI
Published: February 2007

We propose a method for the design of electronic bursting neurons, based on a simple conductance neuron model. A burster is a particular class of neuron that displays fast spiking regimes alternating with resting periods. Our method is based on the use of an electronic circuit that implements the well-known Morris–Lecar neuron model. We use this circuit as a tool of analysis to explore some regions of the parameter space and to contruct several bifurcation diagrams displaying the basic dynamical features of that system. These bifurcation diagrams provide the initial point for the design and implementation of electronic bursting neurons. By extending the phase space with the introduction of a slow driving current, our method allows to exploit the bistabilities which are present in the Morris–Lecar system to the building of different bursting models.
TEXTURE GENERATION USING CELLULAR NEURAL NETWORKS
Authors: DEBIEC PIOTOR , KORNATOWSKI LUKASZ , SLOT KRZYSZTOF , KIM HYONGSUK
Published: February 2007

The following paper introduces an application of Cellular Neural Networks for the generation of predetermined stochastic textures. The key element for the task realization is an appropriate selection of template elements, which should provide a transformation of initial, random CNN state into a stable equilibrium, featuring desired perceptual properties. A template derivation procedure comprises two steps: linear CNN design, followed by a template-refinement procedure that involves nonlinear optimization. In addition, a procedure that extends CNN texture rendition capabilities into a realm of non-pure stochastic textures is proposed.
BIFURCATION PHENOMENA IN COUPLED DYNAMIC SELF-ELECTRO-OPTIC-EFFECT DEVICES
Authors: YAMAMOTO TADAAKI , OHKAWA YOHEI , KITAMOTO TOMOYUKI , NAGAYA TOMOYUKI , NARA SHIGETOSHI
Published: February 2007

Dynamic phenomena in a device network consisting of Dynamic Self-Electro-Optic-Effect Devices (D-SEED) are theoretically predicted and discussed via phenomenological and numerical methods, where each D-SEED element shows nonlinear oscillatory behavior. Analysis is based on a phenomenological model for photocarriers proposed in previous works by one of the authors and it treats a set of diffusively coupled nonlinear rate equations for the photocarrier density of each D-SEED.
A COMMON PHENOMENON IN CHAOTIC SYSTEMS LINKED BY TIME DELAY
Authors: YU PEI , XU FEI
Published: February 2007

In this paper, we report a common phenomenon observed in chaotic systems linked by time delay. Recently, the Lorenz chaotic system has been extended to the family of Lorenz systems which includes the Chen and Lü systems. These three chaotic systems, corresponding to different sets of system parameter values, are topologically different. With the aid of numerical simulations, we have surprisingly found that a simple time delay, directly applied to one or more state variables, transforms the Lorenz system to the generalized Chen system or the generalized Lü system without any parameter changes. The existence of this phenomenon has also been found in other known chaotic systems: the Rössler system, the Chua's circuit and the 4-Liu system. This finding has shown a common characteristic of chaotic systems: a new chaotic "branch" can be created from a chaotic attractor by simply adding a time delay.
LIMIT CYCLES FOR GENERALIZED ABEL EQUATIONS
Authors: GASULL ARMENGOL , GUILLAMON ANTONI
Published: February 2007

This paper deals with the problem of finding upper bounds on the number of periodic solutions of a class of one-dimensional nonautonomous differential equations: those with the right-hand sides being polynomials of degree n and whose coefficients are real smooth one-periodic functions. The case n = 3 gives the so-called Abel equations which have been thoroughly studied and are well understood. We consider two natural generalizations of Abel equations. Our results extend previous works of Lins Neto and Panov and try to step forward in the understanding of the case n > 3. They can be applied, as well, to control the number of limit cycles of some planar ordinary differential equations.
Cardioprotective effect of rosuvastatin in vivo is dependent on inhibition of geranylgeranyl pyrophosphate and altered RhoA membrane translocation
Authors: Bulhak Aliaksandr , Roy Joy , Hedin Ulf , Sjöquist Per-Ove , Pernow John
Published: February 2007

Hydroxymethyl glutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) protect the myocardium against ischemia-reperfusion injury via a mechanism unrelated to cholesterol lowering. Statins may inhibit isoprenylation and thereby prevent activation of proteins such as RhoA. We hypothesized that statins protect the myocardium against ischemia-reperfusion injury via a mechanism involving inhibition of geranylgeranyl pyrophosphate synthesis and translocation of RhoA to the plasma membrane. Sprague-Dawley rats were given either the HMG-CoA reductase inhibitor rosuvastatin, geranylgeranyl pyrophosphate dissolved in methanol, the combination of rosuvastatin and geranylgeranyl pyrophosphate, rosuvastatin and methanol, or distilled water (control) by intraperitoneal injection for 48 h before ischemia-reperfusion. Animals were anesthetized and either subjected to 30 min of coronary artery occlusion followed by 2 h of reperfusion whereat infarct size was determined, or the expression of RhoA protein was determined in cytosolic and membrane fractions of nonischemic myocardium. There were no significant differences in hemodynamics between the control group and the other groups before ischemia or during ischemia and reperfusion. The infarct size was 80 ± 3% of the area at risk in the control group. Rosuvastatin reduced infarct size to 64 ± 2% ( P < 0.001 vs. control). Addition of geranylgeranyl pyrophosphate (77 ± 2%, P < 0.01 vs. rosuvastatin) but not methanol (65 ± 2%, not significant vs. rosuvastatin) abolished the cardioprotective effect of rosuvastatin. Geranylgeranyl pyrophosphate alone did not affect infarct size per se (84 ± 2%). Rosuvastatin increased the cytosol-to-membrane ratio of RhoA protein in the myocardium ( P < 0.05 vs. control). These changes were abolished by addition of geranylgeranyl pyrophosphate. We conclude that the cardioprotection and the increase of the RhoA cytosol-to-membrane ratio induced by rosuvastatin in vivo are blocked by geranylgeranyl pyrophosphate. The inhibition of geranylgeranyl pyrophosphate formation and subsequent modulation of cytosol/membrane-bound RhoA are of importance for the protective effect of statins against myocardial ischemia-reperfusion injury.
The extensive length-force relationship of porcine airway smooth muscle
Authors: Smolensky Alexander V. , Ford Lincoln E.
Published: February 2007

The full functional length range of trachealis muscle was measured to identify a precise reference length and to assess the length changes that the myofilament lattice can accommodate. The initial reference length ( L10%) was that where rest tension equaled 10% of total force (passive tension plus active force). Total force at this length served as a force reference (Fref = 219 ± 12 kPa, N = 7). Muscles initially adapted at L10% for 30–60 min had no rest tension when shortened to <0.9 L10%. Passive tension rose steeply and linearly with slope 11.2 Fref/ L10% at lengths >1.04 L10%. Rest tension at 1.1 L10% declined by <10% over 1 h. The steep slope and stability of rest tension at long lengths suggest that a parameter of the slope could serve as a precise, reproducible reference length. Active force was nearly constant at lengths 0.33–1.0 L10% and declined steeply at lengths between 0.1 and 0.2 L10%, extrapolating to zero at 0.076 L10%. Muscles visibly reextended during relaxation at lengths <0.25 L10%. At long lengths, force extrapolated to zero at 1.175 L10%. The >15-fold length range (0.076–1.175 L10%) for force generation and nearly constant force over a greater than threefold length range is likely produced by several structural accommodations, including filament sliding, an increased number of sliding filaments in series, and increased length of passive structures in series with the sliding filaments. Visible reextension during relaxation suggests that the lattice does not undergo plastic adaptations at lengths <25% L10% and that lattice plasticity is limited to a three- to fourfold length range.
Carotid artery pulse wave time characteristics to quantify ventriculoarterial responses to orthostatic challenge
Authors: Reesink Koen D. , Hermeling Evelien , Hoeberigs M. Christianne , Reneman Robert S. , Hoeks Arnold P. G.
Published: February 2007

Central blood pressure waveforms contain specific features related to cardiac and arterial function. We investigated posture-related changes in ventriculoarterial hemodynamics by means of carotid artery (CA) pulse wave analysis. ECG, brachial cuff pressure, and common CA diameter waveforms (by M-mode ultrasound) were obtained in 21 healthy volunteers (19–30 yr of age, 10 men and 11 women) in supine and sitting positions. Pulse wave analysis was based on a timing extraction algorithm that automatically detects acceleration maxima in the second derivative of the CA pulse waveform. The algorithm enabled determination of isovolumic contraction period (ICP) and ejection period (EP): ICP = 43 ± 8 (SD) ms (4-ms precision), and EP = 302 ± 16 (SD) ms (5-ms precision). Compared with the supine position, in the sitting position diastolic blood pressure (DBP) increased by 7 ± 4 mmHg ( P < 0.001) and R-R interval decreased by 49 ± 82 ms ( P = 0.013), reflecting normal baroreflex response, whereas EP decreased to 267 ± 19 ms ( P < 0.001). Shortening of EP was significantly correlated to earlier arrival of the lower body peripheral reflection wave ( r2 = 0.46, P < 0.001). ICP increased by 7 ± 7 ms ( P < 0.001), the ICP-to-EP ratio increased from 14 ± 3% (supine) to 19 ± 3% ( P < 0.001) and the DBP-to-ICP ratio decreased by 7% ( P = 0.023). These results suggest that orthostasis decreases left ventricular output as a result of arterial wave reflections and, presumably, reduced cardiac preload. We conclude that CA ultrasound and pulse wave analysis enable noninvasive quantification of ventriculoarterial responses to changes in posture.
Enhancement of fat metabolism by repeated bouts of moderate endurance exercise
Authors: Goto Kazushige , Ishii Naokata , Mizuno Ayuko , Takamatsu Kaoru
Published: February 2007

This study compared the fat metabolism between “a single bout of prolonged exercise” and “repeated bouts of exercise” of equivalent exercise intensity and total exercise duration. Seven men performed three trials: 1) a single bout of 60-min exercise (Single); 2) two bouts of 30-min exercise, separated by a 20-min rest between exercise bouts (Repeated); and 3) rest. Each exercise was performed with a cycle ergometer at 60% of maximal oxygen uptake. In the Single and Repeated trials, serum glycerol, growth hormone, plasma epinephrine, and norepinephrine concentrations increased significantly ( P < 0.05) during the first 30-min exercise bout. In the Repeated trial, serum free fatty acids (FFA), acetoacetate, and 3-hydroxybutyrate concentrations showed rapid increases ( P < 0.05) during a subsequent 20-min rest period. During the second 30-min exercise bout, FFA and epinephrine responses were significantly greater in the Repeated trial than in the Single trial ( P < 0.05). Moreover, the Repeated trial showed significantly lower values of insulin and glucose than the Single trial. During the 60-min recovery period after the exercise, FFA, glycerol, and 3-hydroxybutyrate concentrations were significantly higher in the Repeated trial than in the Single trial ( P < 0.05). The relative contribution of fat oxidation to the energy expenditure showed significantly higher values ( P < 0.05) in the Repeated trial than in the Single trial during the recovery period. These results indicate that repeated bouts of exercise cause enhanced fat metabolism compared with a single bout of prolonged exercise of equivalent total exercise duration.
Role of pleural pressure in the coupling between the intercostal muscles and the ribs
Authors: Troyer André De , Leduc Dimitri
Published: February 2007

The inspiratory intercostal muscles elevate the ribs and thereby elicit a fall in pleural pressure (ΔPpl) when they contract. In the present study, we initially tested the hypothesis that this ΔPpl does, in turn, oppose the rib elevation. The cranial rib displacement (Xr) produced by selective activation of the parasternal intercostal muscle in the fourth interspace was measured in dogs, first with the rib cage intact and then after ΔPpl was eliminated by bilateral pneumothorax. For a given parasternal contraction, Xr was greater after pneumothorax; the increase in Xr per unit decrease in ΔPpl was 0.98 ± 0.11 mm/cmH2O. Because this relation was similar to that obtained during isolated diaphragmatic contraction, we subsequently tested the hypothesis that the increase in Xr observed during breathing after diaphragmatic paralysis was, in part, the result of the decrease in ΔPpl, and the contribution of the difference in ΔPpl to the difference in Xr was determined by using the relation between Xr and ΔPpl during passive inflation. With diaphragmatic paralysis, Xr during inspiration increased approximately threefold, and 47 ± 8% of this increase was accounted for by the decrease in ΔPpl. These observations indicate that 1) ΔPpl is a primary determinant of rib motion during intercostal muscle contraction and 2) the decrease in ΔPpl and the increase in intercostal muscle activity contribute equally to the increase in inspiratory cranial displacement of the ribs after diaphragm paralysis.
Recruitment of old genes to new functions: evidences obtained by comparing the orthologues of human XLMR genes in mouse and chicken
Authors: Kohn M. , Kehrer-Sawatzki H. , Steinbach P. , Marshall Graves J.A. , Hameister H.
Published: February 2007

Gene mapping data indicate that the human X chromosome is enriched in genes that affect both, higher cognitive efficiency and reproductive success. This raises the question whether these functions are ancient, or whether conserved X-linked genes were recruited to new functions. We have studied three X-linked mental retardation (XLMR) genes by RNA in situ hybridization in mouse and in chicken, in which these genes are autosomal: Rho guanine nucleotide exchange factor 6 (ARHGEF6), oligophrenin (OPHN1), and p21 activated kinase 3 (PAK3). In the mouse these genes are specifically expressed in telencephalic regions. Their orthologues in the chicken gave patterns of similar specificity in ancient parts of the brain, i.e. cerebellum and mesencephalon, but were not expressed in the telencephalon. Also in the testes, specific expression was only found in mouse, not in chicken. These data are interpreted such that certain genes on the X chromosome gained novel functions during evolution.
Telomeric DNA localization on dinoflagellate chromosomes: structural and evolutionary implications
Authors: Alverca E. , Cuadrado A. , Jouve N. , Franca S. , Moreno Díaz de la Espina S.
Published: February 2007

Dinoflagellates are eukaryotic microalgae with distinct chromosomes throughout the cell cycle which lack histones and nucleosomes. The molecular organization of these chromosomes is still poorly understood. We have analysed the presence of telomeres in two evolutionarily distant and heterogeneous dinoflagellate species (Prorocentrum micans and Amphidinium carterae) by FISH with a probecontaining the Arabidopsis consensus telomeric sequence. Telomere structures were identified at the chromosome ends of both species during interphase and mitosis and were frequently associated with the nuclear envelope. These results identify for the first time telomere structures in dinoflagellate chromosomes, which are formed in the absence of histones. The presence of telomeres supports the linear nature of dinoflagellate chromosomes.
Mapping platypus SOX genes; autosomal location of SOX9 excludes it from sex determining role
Authors: Wallis M.C. , Delbridge M.L. , Pask A.J. , Alsop A.E. , Grützner F. , O’Brien P.C.M. , Rens W. , Ferguson-Smith M.A. , Graves J.A.M.
Published: February 2007

In the absence of an SRY orthologue the platypus sex determining gene is unknown, so genes in the human testis determining pathway are of particular interest as candidates. SOX9 is an attractive choice because SOX9 deletions cause male-to-female sex reversal in humans and mice, and SOX9 duplications cause female-to-male sex reversal. We have localized platypus SOX9, as well as the related SOX10, to platypus chromosomes 15 and 10, respectively, the first assignments to these platypus chromosomes, and the first comparative mapping markers from human chromosomes 17 and 22. The autosomal localization of platypus SOX9 in this study contradicts the hypothesis that SOX9 acts as the sex determining switch in platypus.
Rapid Leptin Elevation after Initiation of Olanzapine?
Authors: Wang Hsuan-Chi , Chen Po See , Lee I Hui , Yang Yen Kuang , Yeh Tzung Lieh , Lu Ru-Band
Published: February 2007

Weight gain is a common adverse effect associated with olanzapine treatment. Another side effect of olanzapine treatment is a significant increase in circulating leptin levels. This preliminary study monitored the changes in leptin levels for 2 weeks after olanzapine treatment had been initiated. The relationship between the changes in circulating leptin levels and alterations in body weight in 9 patients with schizophrenia who received olanzapine was examined. The results showed that olanzapine may cause a surge in circulating leptin levels before weight gain is manifested. Moreover, higher pretreatment circulating leptin levels predicted lower weight gains after olanzapine treatments (r = –0.93; p < 0.05) after controlling for the effect of sex.
Attention Deficit Hyperactivity Disorder Symptoms in Pervasive Developmental Disorders: Association with Autistic Behavior Domains and Coexisting Psychopathology
Authors: Holtmann Martin , Bölte Sven , Poustka Fritz
Published: February 2007

Background: Symptoms as in attention deficit hyperactivity disorder (ADHD) are frequent among individuals with pervasive developmental disorders (PDD). The aim of the present study was to examine the impact of inattention, hyperactivity and impulsivity on the clinical phenotype of children and adolescents with PDD. Sampling and Methods: A total of 182 subjects (41 females) diagnosed as having PDD were split into a high (PDD+) and a lower (PDD) attention problem group using the median of the Child Behavior Checklist (CBCL) syndrome scale ‘attention problems’ (median T score = 75). The groups were compared with regard to the degree of coexisting psychopathology, as measured by the remaining 7 CBCL subscales, and autistic core features assessed by the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule using a multivariate analysis of covariance adjusted for age, IQ and socioeconomic status. Results: The PDD+ subjects exhibited a significantly higher degree of general psychopathology than the subjects in the PDD subgroup, regarding both internalizing and externalizing symptoms. In addition, the PDD+ subgroup tended to exhibit more impairments on the social interaction scale of the ADI-R. Conclusions: Clinicians should adjust treatment plans to ensure comprehensive and effective treatment for both PDD and associated ADHD. A dual diagnosis may be essential to the implementation of effective treatments.
Interrelationship between Physical Activity, Symptomatology of Upper Respiratory Tract Infections, and Depression in Elderly People
Authors: Kostka Tomasz , Prączko Katarzyna
Published: February 2007

Background: It has been suggested that regular moderate physical activity (PA) promotes resistance to upper respiratory tract infections (URTI). In an older population, this relationship should be examined in a wider concept of multiple factors potentially able to influence infection rate and reported symptomatology. Especially, the impact of depression should be taken into consideration. Objective: To examine the association of URTI with PA and depressive symptoms in the elderly, and whether this relationship persists after controlling for confounders attributable to comorbidities, functional status, and cognitive function. Methods: One hundred and forty-five subjects (80 women and 65 men) between 66 and 79 years of age were randomly chosen from all inhabitants of one district of the city of Lodz (Poland). They participated in baseline and 1-year follow-up examinations and completed the infection questionnaire during the whole year. Log books for daily recording of the URTI symptomatology were used in the prospective design. The PA was assessed by the Seven-Day Physical Activity Recall Questionnaire. Geriatric Depression Scale and other elements of the comprehensive geriatric assessment were also used. Results: In bivariate relationships, the number of episodes per year and the number of days with URTI per year were significantly negatively associated with several baseline and follow-up PA indices and directly related to baseline and follow-up depression scores. In multivariate relationships, after controlling for other elements of the comprehensive geriatric assessment, both PA and depression contributed to URTI symptomatology, while URTI symptoms predicted final PA scores, and changes in PA added to the follow-up depression score. Conclusions: These results indicate that in elderly subjects the symptomatology of URTI is interrelated with their habitual PA and depressive symptomatology. Less active and more depressed subjects develop more URTI symptoms during 1-year follow-up. This URTI symptomatology, together with the baseline PA and the depressive status, contributes to the follow-up PA and depression scores.
Mechanisms Underlying the Impairment of Ischemia-Induced Neovascularization in Matrix Metalloproteinase 2–Deficient Mice
Authors: Cheng Xian Wu , Kuzuya Masafumi , Nakamura Kae , Maeda Keiko , Tsuzuki Michitaka , Kim Weon , Sasaki Takeshi , Liu Zexuan , Inoue Natsuo , Kondo Takahisa , Jin Hai , Numaguchi Yasushi , Okumura Kenji , Yokota Mitsuhiro , Iguchi Akihisa , Murohara Toyoaki
Published: February 2007

Matrix metalloproteinases (MMPs) have been implicated in the process of neovascularization. However, the exact roles of individual MMPs in vessel formation are poorly understood. To study the putative role of MMP-2 in ischemia-induced neovascularization, a hindlimb ischemia model was applied to MMP-2
+/+
and MMP-2
−/−
mice. Serial laser Doppler blood-flow analysis revealed that the recovery of the ischemic/normal blood-flow ratio in MMP-2
−/−
young and old mice remained impaired throughout the follow-up period. At day 35, microangiography and anti–
l
-lectin immunohistochemical staining revealed lesser developed collateral vessels and capillary formation in both old and young MMP-2
−/−
mice compared with the age-matched MMP-2
+/+
mice. An aortic-ring culture assay showed a markedly impaired angiogenic response in MMP-2
−/−
mice, which was partially recovered by supplementation of the culture medium with recombinant MMP-2. Aorta-derived endothelial cells or bone marrow–derived endothelial progenitor cell (EPC)-like c-Kit
+
cells from MMP-2
−/−
showed marked impairment of invasive or/and proliferative abilities. At day 7, plasma and ischemic tissues of vascular endothelial growth factor protein were reduced in MMP-2
−/−
. Flow cytometry showed that the numbers of EPC-like CD31
+
c-Kit
+
cells in peripheral blood markedly decreased in MMP-2–deficient mice. Transplantation of bone marrow–derived mononuclear cells from MMP-2
+/+
mice restored neovascularization in MMP-2
−/−
young mice. These data suggest that MMP-2 deficiency impairs ischemia-induced neovascularization through a reduction of endothelial cell and EPC invasive and/or proliferative activities and EPC mobilization.
Monocyte/Macrophage Suppression in CD11b Diphtheria Toxin Receptor Transgenic Mice Differentially Affects Atherogenesis and Established Plaques
Authors: Stoneman Victoria , Braganza Denise , Figg Nichola , Mercer John , Lang Richard , Goddard Martin , Bennett Martin
Published: February 2007

Although monocytes/macrophages are considered important in atherogenesis, their role in established plaques is unclear. For example, macrophage content is associated with plaque instability, but their loss through cell death is observed at sites of plaque rupture. To examine the role of monocytes/macrophages in atherosclerosis, we developed CD11b–diphtheria toxin (DT) receptor (DTR) transgenic mice, whereby administration of DT selectively kills monocytes/macrophages. DT treatment reduced peripheral blood monocytes and tissue macrophages and inhibited macrophage function in CD11b-DTR mice and apolipoprotein E–null (apoE
−/−
) mice transplanted with CD11b-DTR bone marrow. In atherogenesis experiments, DT markedly reduced plaque development and altered plaque composition, reducing collagen content and necrotic core formation. In mice with established plaques, acute DT treatment induced macrophage apoptosis and reduced macrophage content but did not induce plaque inflammation, thrombosis, or rupture. Furthermore, despite a 50% reduction in monocytes, chronic DT treatment of these mice did not alter plaque extent or composition, most likely because of ongoing recruitment/proliferation of monocytes with recovery of macrophage content. We conclude that monocytes/macrophages are critical to atherogenesis, but established plaques are more resistant to reductions in monocytes.
Alternative Splicing of Ryanodine Receptors Modulates Cardiomyocyte Ca
2+
Signaling and Susceptibility to Apoptosis
Authors: George Christopher H. , Rogers Sarah A. , Bertrand Benedicte M.A. , Tunwell Richard E.A. , Thomas N. Lowri , Steele Derek S. , Cox Eryl V. , Pepper Christopher , Hazeel Carolyn J. , Claycomb William C. , Lai F. Anthony
Published: February 2007

Ca
2+
release via type 2 ryanodine receptors (RyR2) regulates cardiac function. Molecular cloning of human RyR2 identified 2 alternatively spliced variants, comprising 30- and 24-bp sequence insertions; yet their role in shaping cardiomyocyte Ca
2+
signaling and cell phenotype is unknown. We profiled the developmental regulation and the tissue and species specificity of these variants and showed that their recombinant expression in HL-1 cardiomyocytes profoundly modulated nuclear and cytoplasmic Ca
2+
release. All splice variants localized to the sarcoplasmic reticulum, perinuclear Golgi apparatus, and to finger-like invaginations of the nuclear envelope (nucleoplasmic reticulum). Strikingly, the 24-bp splice insertion that was present at low levels in embryonic and adult hearts was essential for targeting RyR2 to an intranuclear Golgi apparatus and promoted the intracellular segregation of this variant. The amplitude variability of nuclear and cytoplasmic Ca
2+
fluxes were reduced in nonstimulated cardiomyocytes expressing both 30- and 24-bp splice variants and were associated with lower basal levels of apoptosis. Expression of RyR2 containing the 24-bp insertion also suppressed intracellular Ca
2+
fluxes following prolonged caffeine exposure (1 mmol/L, 16 hours) that protected cells from apoptosis. The antiapoptotic effects of this variant were linked to increased levels of Bcl-2 phosphorylation. In contrast, RyR2 containing the 30-bp insertion, which was abundant in human embryonic heart but was decreased during cardiac development, did not protect cardiomyocytes from caffeine-evoked apoptosis. Thus, we provide the first evidence that RyR2 splice variants exquisitely modulate intracellular Ca
2+
signaling and are key determinants of cardiomyocyte apoptotic susceptibility.
Hyperbaric Oxygen-Induced Attenuation of Hemorrhagic Transformation After Experimental Focal Transient Cerebral Ischemia
Authors: Qin Zhiyong , Karabiyikoglu Murat , Hua Ya , Silbergleit Robert , He Yangdong , Keep Richard F. , Xi Guohua
Published: February 2007

Background and Purpose—

An increased risk of hemorrhagic transformation is a major factor limiting the use of tissue plasminogen activator for stroke. Increased hemorrhagic transformation is also found in animals undergoing transient focal cerebral ischemia with hyperglycemia; this study examined whether hyperbaric oxygen (HBO) could reduce such hemorrhagic transformation in a rat model.

Methods—

Rats received an injection of 50% glucose (6 mL/kg intraperitoneally) and had a middle cerebral artery occlusion 10 minutes later. Rats were treated with HBO (3 ATA for 1 hour) 30 minutes after middle cerebral artery occlusion. Control rats received normobaric room air. Rats underwent reperfusion 2 hours after middle cerebral artery occlusion. Blood–brain barrier permeability (Evans blue), hemorrhagic transformation (hemoglobin content), brain edema, infarct volume, and mortality were measured.

Results—

HBO treatment reduced Evans blue leakage in the ipsilateral hemisphere (28.4±3.5 versus 71.8±13.1 μg/g in control group,
P
<0.01) 2 hours after reperfusion and hemorrhagic transformation (0.13±0.13 versus 0.31±0.28 mg hemoglobin in the control group,
P
<0.05) 22 hours later. Mortality was less in the HBO group (4% versus 27% in controls,
P
<0.05). Mean infarct volume and swelling in the caudate were also less in HBO-treated rats (
P
<0.05), but HBO failed to reduce brain water content in the ipsilateral hemisphere (
P
>0.05).

Conclusions—

Early intraischemic HBO treatment reduces the blood–brain barrier disruption, hemorrhagic transformation, and mortality after focal cerebral ischemia suggesting that HBO could be used to reduce hemorrhagic conversion in patients with stroke.