bluuebunny/crossref_metadata_2025 huggingface dataset:
BOUNDARY ELEMENT METHOD FOR ISOTROPIC MEDIA WITH RANDOM SHEAR MODULI
Authors: WAUBKE HOLGER
Published: May 2005

Green's functions for elastic solids with random properties are usually derived by means of the perturbation method. This paper deals with a new approach that has the potential to deal with a large variability of random shear modulus based on the transformation of a polynomial chaos. The deterministic Green's functions for stresses and displacements and the principal values in the boundary integrals caused by a pressure load on the surface are nonlinear transformations of the random variables. A series of transformations of the polynomial chaos is used to transform significant parts of the equation. The first operation is a projection of the log normal distributed shear modulus to a series of Hermite's polynomials based on a Gaussian variable. The second operation is the determination of an arbitrary potential of the wave velocity. The last operation, similar to the first one, consists in the determination of an exponential function depending on the inverse of the wave velocity. These operations, together with multiplications and summations, transform the complete relation from the random shear modulus to Green's functions and principal values. The inversion of the system matrix is already derived for the random finite element approach. The operations are independent of the specific problem and can be applied to almost all acoustic media and similar nonlinear problems.
THEORY AND BOUNDARY ELEMENT METHODS FOR NEAR-FIELD ACOUSTIC HOLOGRAPHY
Authors: DELILLO THOMAS , HRYCAK TOMASZ , ISAKOV VICTOR
Published: May 2005

We consider the problem of recovering surface vibrations from acoustic pressure measurements taken in the interior or the exterior of a region. We give two formulations of the problem. One is based on a representation of the pressure as layer potentials and the other is based on approximation by a class of specific solutions to the Helmholtz equation. Boundary element methods are developed to approximate the integral operators. A conjugate gradient algorithm based on Lanczos bidiagonalization is applied to compute regularized solutions to the ill-conditioned equations in the presence of measurement errors. Numerical examples which compare the two formulations are presented.
RECONSTRUCTION OF SOUND SOURCES BY MEANS OF AN INVERSE BOUNDARY ELEMENT FORMULATION
Authors: NOLTE BODO
Published: May 2005

The self-developed Boundary Element code BEMCUP-3D solves structural-dynamic and acoustic problems as well as fluid-structure-interaction-phenomena in the frequency domain. Attainable outputs of this program are e.g. the system matrices. The inverse acoustic problem (sound source identification) is considered without inversion of matrices. The envelope surface (measurement surface), which encloses the entire arbitrarily shaped sound source, is treated as an exterior problem. The Dirichlet data on this surface or boundary are given from the proper sound pressure distribution of the sound source, which is also an exterior problem. This ensures that the corresponding velocity values on the measurement surface are exactly the same for both problems. Next the region between the sound source (an arbitrarily vibrating structure) and the envelope surface (a measurement surface in experimental investigations) is treated as an interior problem. The boundary conditions on the outer surface (measurement surface) for this problem are of Dirichlet type and the already available Neumann data, the sound pressure and the velocity distributions. An algorithm makes sure that after solving the unknown sound pressure and velocity values of the sound source are situated in the solving vector. Simple sound sources enable to investigate the stability, an optimal shape and an optimal position of the measurement surface.
The Hydromagnetic Nature of Solar Coronal Mass Ejections
Authors: Zhang Mei , Low Boon Chye
Published: May 2005

▪ Abstract  Solar coronal mass ejections (CMEs) are a major form of activity on the Sun. A CME takes 1015-16g of plasma from the low corona into the solar wind, to disturb the near-Earth space if the CME direction is favorable. We summarize current observations and ideas of CME physics to provide a hydromagnetic view of the CMEs as the products of continual magnetic flux emergence and an interplay between magnetic reconnection and approximate magnetic-helicity conservation in the corona. Each flux emergence brings helicity to accumulate additively in a coronal structure while excess magnetic energy is flared away by reconnection. Self-confinement eventually fails with a CME shedding the accumulated helicity out of the low corona to enable the field to reach the minimum-energy state. Similar evolutionary processes may occur in other magnetic stars and galaxies.
Characteristics of new Staphylococcus aureus-RBC adhesion mechanism independent of fibrinogen and IgG under hydrodynamic shear conditions
Authors: Shin Pyong Kyun , Pawar Parag , Konstantopoulos Konstantinos , Ross Julia M.
Published: May 2005

Staphylococcus aureus infection begins when bacterial cells circulating in blood adhere to components of the extracellular matrix or endothelial cells of the host and initiate colonization. S. aureus is known to exhibit extensive interactions with platelets. S. aureus is also known to bind to red blood cells (RBCs) in the presence of plasma proteins, such as fibrinogen and IgG. Herein we report a new binding mechanism of S. aureus to RBC independent of those plasma proteins. To characterize the new adhesion mechanism, we experimentally examine the binding kinetics and molecular constituents mediating the new adhesive interactions between S. aureus and RBCs under defined shear conditions. The results demonstrate that the receptors for fibrinogen (clumping factor A) and IgG (protein A) of S. aureus are not involved in the adhesion. S. aureus binds to RBCs with maximal adhesion at the shear rate 100 s−1 and decreasing adhesion with increasing shear. The heteroaggregates formed after shear are stable when subjected to the shear rate 2,000 s−1, indicating that intercellular contact time rather than shear forces controls the adhesion at high shear. S. aureus binding to RBC requires plasma, and 10% plasma is sufficient for maximal adhesion. Plasma proteins involved in the cell-cell adhesion, such as fibrinogen, fibronectin, von Willebrand factor, IgG, thrombospondin, laminin, and vitronectin are not involved in the observed adhesion. The extent of heteroaggregation is dramatically reduced on RBC treatment with trypsin, chymotrypsin, or neuraminidase, suggesting that the receptor(s) mediating the heteroaggregation process is a sialylated glycoprotein on RBC surface. Adhesion is divalent cation dependent and also blocked by heparin. This work demonstrates a new mechanism of S. aureus-RBC binding under hydrodynamic shear conditions via unknown RBC sialoglycoprotein(s). The binding requires plasma protein(s) other than fibrinogen or IgG and does not involve the S. aureus adhesins clumping factor A or protein A.
Distinct and sequential upregulation of genes regulating cell growth and cell cycle progression during hepatic ischemia-reperfusion injury
Authors: Barone Sharon , Okaya Tomohisa , Rudich Steve , Petrovic Snezana , Tenrani Kathy , Wang Zhaohui , Zahedi Kamyar , Casero Robert A. , Lentsch Alex B. , Soleimani Manoocher
Published: May 2005

Ischemia-reperfusion injury (IRI) in liver and other organs is manifested as an injury phase followed by recovery and resolution. Control of cell growth and proliferation is essential for recovery from the injury. We examined the expression of three related regulators of cell cycle progression in liver IRI: spermidine/spermine N-acetyltransferase (SSAT), p21 (a cyclin-dependent kinase inhibitor), and stathmin. Mice were subjected to hepatic IRI, and liver tissues were harvested at timed intervals. The expression of SSAT, the rate-limiting enzyme in the polyamine catabolic pathway, had increased fivefold 6 h after IRI and correlated with increased putrescine levels in the liver, consistent with increased SSAT enzymatic activity in IRI. The expression of p21, which is transactivated by p53, was undetectable in sham-operated animals but was heavily induced at 12 and 24 h of reperfusion and declined to undetectable baseline levels at 72 h of reperfusion. The interaction of the polyamine pathway with the p53-p21 pathway was shown in vitro, where activation of SSAT with polyamine analog or the addition of putrescine to cultured hepatocytes induced the expression of p53 and p21 and decreased cell viability. The expression of stathmin, which is under negative transcriptional regulation by p21 and controls cell proliferation and progression through mitosis, remained undetectable at 6, 12, and 24 h of reperfusion and was progressively and heavily induced at 48 and 72 h of reperfusion. Double-immunofluorescence labeling with antibodies against stathmin and PCNA, a marker of cell proliferation, demonstrated colocalization of stathmin and PCNA at 48 and 72 h of reperfusion in hepatocytes, indicating the initiation of cell proliferation. The distinct and sequential upregulation of SSAT, p21, and stathmin, along with biochemical activation of the polyamine catabolic pathway in IRI in vivo and the demonstration of p53-p21 upregulation by SSAT and putrescine in vitro, points to the important role of regulators of cell growth and cell cycle progression in the pathophysiology and/or recovery in liver IRI. The data further suggest that SSAT may play a role in the initiation of injury, whereas p21 and stathmin may be involved in the resolution and recovery after liver IRI.
Regulation of IκB kinase and NF-κB in contracting adult rat skeletal muscle
Authors: Ho Richard C. , Hirshman Michael F. , Li Yangfeng , Cai Dongsheng , Farmer Jocelyn R. , Aschenbach William G. , Witczak Carol A. , Shoelson Steven E. , Goodyear Laurie J.
Published: May 2005

Nuclear factor-κB (NF-κB) is a transcription factor with important roles in regulating innate immune and inflammatory responses. NF-κB is activated through the phosphorylation of its inhibitor, IκB, by the IκB kinase (IKK) complex. Physical exercise elicits changes in skeletal muscle gene expression, yet signaling cascades and transcription factors involved remain largely unknown. To determine whether NF-κB signaling is regulated by exercise in vivo, rats were run on a motorized treadmill for 5–60 min. Exercise resulted in up to twofold increases in IKKα/β phosphorylation in the soleus and red gastrocnemius muscles throughout the time course studied. In red gastrocnemius muscles, NF-κB activity increased 50% 1–3 h after 60 min of treadmill exercise, returning to baseline by 5 h. Contraction of isolated extensor digitorum longus muscles in vitro increased IKKα/β phosphorylation sevenfold and this was accompanied by a parallel increase in IκBα phosphorylation. Additional kinases that are activated by exercise include p38, extracellular-signal regulated protein kinase (ERK), and AMP-activated protein kinase (AMPK). Inhibitors of p38 (SB-203580) and ERK (U-0126) blunted contraction-mediated IKK phosphorylation by 39 ± 4% ( P = 0.06) and 35 ± 10% ( P = 0.09), respectively, and in combination by 76 ± 5% ( P < 0.05), suggesting that these kinases might influence the activation of IKK and NF-κB during exercise. In contrast, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside, an activator of AMPK, had no effect on either IKK or NF-κB activity. In conclusion, acute submaximal exercise transiently stimulates NF-κB signaling in skeletal muscle. This activation is a local event because it can occur in the absence of exercise-derived systemic factors.
Opposite effects of tumor necrosis factor and soluble fibronectin on junctional adhesion molecule-A in endothelial cells
Authors: Martinez-Estrada Ofelia M. , Manzi Luca , Tonetti Paolo , Dejana Elisabetta , Bazzoni Gianfranco
Published: May 2005

Junctional adhesion molecule-A (JAM-A) regulates key inflammatory responses, such as edema formation and leukocyte transmigration. Although it has been reported that the inflammatory cytokine tumor necrosis factor (TNF) causes the disassembly of JAM-A from the intercellular junctions, the mechanism has not been elucidated fully. Here, we report that TNF enhances the solubility of JAM-A in Triton X-100 and increases the amount of Triton-soluble JAM-A dimers at the cell surface but does not change the total levels of cellular JAM-A. Thus we hypothesized that TNF causes the redistribution of JAM-A from the junctions to the cell surface and that junction disassembly is sufficient to account for JAM-A redistribution. Intriguingly, however, even after complete disassembly of the junctions (with EDTA and trypsin), higher levels of JAM-A are detectable at the cell surface (by FACS analysis) in cells that had been previously incubated in the presence of TNF than in its absence. Thus we propose that TNF causes not only the disassembly of JAM-A from the junctions and its subsequent redistribution to the cell surface but also its dispersal in such a way that JAM-A becomes more easily accessible to the antibodies used for FACS analysis. Finally, we evaluated whether soluble fibronectin might attenuate the effects of TNF on JAM-A, as some inflammatory conditions are associated with the depletion of plasma fibronectin. We found that fibronectin reduces the effect of TNF on the disassembly of JAM-A, but not on its dispersal, thus further stressing that disassembly and dispersal can be functionally dissociated.
Nandrolone decanoate modulates cell cycle regulation in functionally overloaded rat soleus muscle
Authors: McClung Joseph M. , Mehl Kristen A. , Thompson Raymond W. , Lowe Larry L. , Carson James A.
Published: May 2005

Functionally overloading rat soleus muscle by synergist ablation induces a rapid increase in mass. Muscle remodeling during the first week of overload is critical for the overload-induced growth. Anabolic steroid modulation of this overload-induced remodeling response is not well understood. The purpose of this study was to determine whether pretreatment with nandrolone decanoate, a clinically administered anabolic steroid, alters muscle morphology and gene expression related to muscle growth during the initiation of functional overload in the rat soleus muscle. Adult (5 mo) male Fisher 344 × Brown Norway rats were randomly assigned to control (Sham), 3-day functional overload (OV), nandrolone decanoate administration (ND), or 3-day functional overload with nandrolone decanoate administration (OV+ND) treatment groups. Morphologically, OV increased the percentage of small (361%) and large (150%) fibers and expanded the ECM 50%. ND administration decreased the 3-day OV induction of small fibers 51% and nuclei associated with the ECM 20%. ND administration also attenuated the induction of cell cycle regulator p21 (64%) and myogenin (37%) mRNAs after 3 days of overload. These data demonstrate that nandrolone decanoate pretreatment can alter morphological and cell cycle regulator expression related to muscle growth at the onset of functional overload.
Exposure to chronic stress downregulates corticosterone responses to acute stressors
Authors: Rich Erin L. , Romero L. Michael
Published: May 2005

We used captive European starlings ( Sturnus vulgaris) to test whether corticosterone responses differed in birds held under normal laboratory conditions or conditions of chronic stress. Surprisingly, both basal corticosterone concentrations and corticosterone responses to acute stress were significantly reduced when birds were chronically stressed. To determine the mechanism underlying this reduced response, animals under both conditions were injected with lactated Ringer’s solution (control), adrenocorticotropin (ACTH), arginine vasotocin (AVT), or dexamethasone (DEX). ACTH increased corticosterone concentrations above stress-induced levels in both cases, although maximum responses were lower in chronically stressed birds. AVT did not augment the corticosterone response under nonchronically stressed conditions, but it did under chronically stressed conditions. DEX reduced maximal corticosterone concentrations in both cases. Neither ovine nor rat corticotropin-releasing factor (CRF) altered normal stress responses. These data indicate that changes in responsiveness of the hypothalamic-pituitary-adrenal axis to ACTH and AVT serve to downregulate corticosterone responses during chronic stress. Furthermore, these data lead to the following hypothesis: ACTH output from the pituitary limits maximum corticosterone concentrations under normal conditions, but reduced AVT release from the hypothalamus regulates lower corticosterone concentrations under chronic stress conditions.
Injection of neuropeptide W into paraventricular nucleus of hypothalamus increases food intake
Authors: Levine Allen S. , Winsky-Sommerer Raphaelle , Huitron-Resendiz Salvador , Grace Martha K. , de Lecea Luis
Published: May 2005

Neuropeptide W (NPW) is an endogenous ligand for G protein-coupled receptor 7 (GPR7). There are two forms of the peptide, designated as neuropeptide W-23 (NPW23) and neuropeptide W-30 (NPW30). In the current study we found that intracerebroventricular administration of NPW23 increased c-Fos immunoreactivity (IR) in a variety of brain sites, many of which are involved in the regulation of feeding. In particular, we noted that c-Fos IR levels were increased in hypocretin-expressing neurons in the perifornical region of the lateral hypothalamus (LH). We then studied whether injection of NPW23 into the paraventricular nucleus of the hypothalamus (PVN) and the LH increased food intake over a 24-h time period. Intra-PVN injection of NPW23 at doses ranging from 0.1 to 3 nmol increased feeding for up to 4 h, and doses ranging from 0.3 to 3 nmol increased feeding for up to 24 h. In contrast, only the 3-nmol dose of NPW23 increased feeding after administration into the LH. Together, these data suggest a modulatory role for NPW in the control of food intake.
N-acetyl-l-cysteine protects intestinal lymphocytes from apoptotic death after acute exercise in adrenalectomized mice
Authors: Quadrilatero Joe , Hoffman-Goetz Laurie
Published: May 2005

Lymphocyte apoptosis has been observed after strenuous exercise. Both glucocorticoids (GC) and reactive oxygen species (ROS) have been suggested to contribute to exercise-induced lymphocyte apoptosis. The aims of this study were to 1) examine the direct contribution of GC during exercise-induced intestinal lymphocyte (IL) apoptosis and 2) determine the contribution of oxidative stress, in the absence of GC, to exercise-induced IL apoptosis. Mice were bilaterally adrenalectomized (ADX) and randomly assigned to receive saline (SAL) or N-acetyl-l-cysteine (NAC) 30 min before treadmill exercise (EX). EX consisted of 90 min of continuous running at a 2° slope (30 min at 22 m/min, 30 min at 25 m/min; and 30 min at 28 m/min), and then killed immediately (Imm) or 24 h (24h) postexercise. Control mice were exposed to a nonexercised (NonEX) condition consisting of treadmill noise and vibration without running. ILs were isolated and measured for apoptotic (phosphatidylserine externalization, mitochondrial membrane depolarization, Bcl-2, caspase 3, and cytosolic cytochrome c) and oxidative stress (H2O2and glutathione) markers. Plasma was analyzed for corticosterone (CORT) by radioimmunoassay. ADX eliminated the exercise-induced elevation in CORT but did not prevent IL apoptosis and cell loss relative to NonEX mice. In contrast, administration of NAC to ADX mice protected ILs from apoptotic cell death and inhibited post-exercise cell loss. These findings suggest that GC are not responsible for exercise-induced apoptosis and cell loss of ILs. The protective effect provided by the antioxidant NAC strongly suggest that oxidative stress is the primary pathway for IL apoptosis and cell loss after strenuous exercise.
Subcutaneous Po2 as an index of the physiological limits for hemodilution in the rat
Authors: Pearce Frederick J. , Waasdorp Christine , Hufnagel Howard , Burris David , DeFeo Joseph , Soballe Peter , Drucker William R.
Published: May 2005

This study was designed to test the hypothesis that changes in subcutaneous Po2 (PscO2) during progressive hemodilution will reliably predict a “critical point” at which tissue O2 consumption (V̇o2) becomes dependent on O2 delivery (Q̇o2). Twelve pentobarbital-anesthetized male Sprague-Dawley rats (315–375 g) underwent stepwise exchange of plasma for blood (1.5 ml of plasma for each 1 ml of blood lost). The initial exchange was equal to 25% of the estimated circulatory blood volume, and each subsequent exchange was equal to 10% of the estimated circulatory blood volume. After nine exchanges, the hematocrit (Hct) fell from 42 ± 1 to 6 ± 1%. Cardiac output and O2 extraction rose significantly. PscO2 became significantly reduced ( P < 0.05) after exchange of 45% of the blood volume (Hct = 16 ± 1%). V̇o2 became delivery dependent when Q̇o2 fell below 21 ml·min−1·kg body wt−1 (mean Hct = 13 ± 1%). Eight control rats undergoing 1:1 blood-blood exchange showed no change in PscO2, pH, HCO3−, or hemodynamics. Measurement of PscO2 may be a useful guide to monitor the adequacy of Q̇o2 during hemodilution.
Decreased intestinal polyp multiplicity is related to exercise mode and gender in ApcMin/+ mice
Authors: Mehl Kristen A. , Davis J. Mark , Clements Julie M. , Berger Franklin G. , Pena Maria M. , Carson James A.
Published: May 2005

Moderate-intensity treadmill running can alter male Apc Min/+ mouse polyp formation. This purpose of this study was to examine whether exercise mode differentially affects Apc Min/+ mouse intestinal polyp development in male and female mice. Male and female Apc Min/+ mice were randomly assigned to control, treadmill (18 m/min; 60 min/day; 6 days/wk), or voluntary wheel running (24-h access) groups. Nine weeks of training decreased total intestinal polyps by 29% in male treadmill runners (66 ± 9; P = 0.038) compared with male controls (93 ± 7). The number of large polyps (≥1-mm diameter) were also reduced by 38% in male treadmill runners (49 ± 6; P = 0.005) compared with male controls (79 ± 6). Treadmill running in female Apc Min/+ mice and wheel running in both genders did not affect polyp number or size. Spleen weight decreased in male treadmill runners (91 ± 9 mg; P = 0.011) and wheel runners (75 ± 6 mg; P = 0.004) compared with controls (141 ± 13 mg). Plasma IL-6 was reduced by 96% in male treadmill runners (1.2 ± 0.6 pg/ml) and 78% in male wheel runners (6.6 ± 3.3 pg/ml) compared with control mice (27.9 ± 2.8 pg/ml; P < 0.05). Female mice responded similarly with an 86% decrease in plasma IL-6 with treadmill running (3.2 ± 1.2 pg/ml) and 90% decrease with wheel running (2.9 ± 2.0 pg/ml) compared with control mice (21.1 ± 5.3 pg/ml; P < 0.05). The crypt depth-to-villus height ratio in the intestine, an indirect marker of intestinal inflammation, decreased by 21 ( P = 0.024) and 24% ( P = 0.029), respectively, in male and female treadmill runners but not wheel runners. Physical activity-induced attenuation of intestinal polyp number and size is dependent on exercise mode and differs between genders. The modulation of systemic and intestinal inflammation may also depend on exercise mode.
AP180 Maintains the Distribution of Synaptic and Vesicle Proteins in the Nerve Terminal and Indirectly Regulates the Efficacy of Ca2+-Triggered Exocytosis
Authors: Bao Hong , Daniels Richard W. , MacLeod Gregory T. , Charlton Milton P. , Atwood Harold L. , Zhang Bing
Published: May 2005

AP180 plays an important role in clathrin-mediated endocytosis of synaptic vesicles (SVs) and has also been implicated in retrieving SV proteins. In Drosophila, deletion of its homologue, Like-AP180 (LAP), has been shown to increase the size of SVs but decrease the number of SVs and transmitter release. However, it remains elusive whether a reduction in the total vesicle pool directly affects transmitter release. Further, it is unknown whether the lap mutation also affects vesicle protein retrieval and synaptic protein localization and, if so, how it might affect exocytosis. Using a combination of electrophysiology, optical imaging, electron microscopy, and immunocytochemistry, we have further characterized the lap mutant and hereby show that LAP plays additional roles in maintaining both normal synaptic transmission and protein distribution at synapses. While increasing the rate of spontaneous vesicle fusion, the lap mutation dramatically reduces impulse-evoked transmitter release at steps downstream of calcium entry and vesicle docking. Notably, lap mutations disrupt calcium coupling to exocytosis and reduce calcium cooperativity. These results suggest a primary defect in calcium sensors on the vesicles or on the release machinery. Consistent with this hypothesis, three vesicle proteins critical for calcium-mediated exocytosis, synaptotagmin I, cysteine-string protein, and neuronal synaptobrevin, are all mislocalized to the extrasynaptic axonal regions along with Dap160, an active zone marker (nc82), and glutamate receptors in the mutant. These results suggest that AP180 is required for either recycling vesicle proteins and/or maintaining the distribution of both vesicle and synaptic proteins in the nerve terminal.
Novel Role of Brain Stem Pedunculopontine Tegmental Adenylyl Cyclase in the Regulation of Spontaneous REM Sleep in the Freely Moving Rat
Authors: Datta Subimal , Prutzman Sarah L.
Published: May 2005

Physiological activation of kainate receptors and GABABreceptors within the pedunculopontine tegmentum (PPT) is involved in regulation of rapid-eye-movement (REM) sleep. Because these two types of receptors may also directly and/or indirectly activate the intracellular cyclic adenosine monophosphate (cAMP) signaling pathway, we hypothesized that this signaling pathway may be involved in the PPT to regulate spontaneous REM sleep. To test this hypothesis, four different doses (0.25, 0.50, 0.75, and 1.0 nmol) of a specific adenylyl cyclase (AC) inhibitor, 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), were microinjected bilaterally (100 nl/site) into the PPT, and the effects on REM sleep in freely moving chronically instrumented rats were quantified. By comparing alterations in the patterns of REM sleep after control injections of vehicle or one of the four different doses of SQ22536, the contributions made by each dose of SQ22536 to REM sleep were evaluated. The results demonstrated that the local microinjection of AC inhibitor SQ22536 into the PPT decreased the total amount of REM sleep for 3 h and increased slow-wave sleep (SWS) for 2 h in a dose-dependent manner. This reduction in REM sleep was due to increased latency and decreased frequency of REM sleep episodes. These results provide evidence that inhibition of AC within the PPT can successfully reduce REM sleep. These findings suggest that activation of the cAMP-signaling pathway within the cholinergic cell compartment of the PPT is an intracellular biochemical/molecular step for generating REM sleep in the freely moving rat.
Quantification of Motor Cortex Activity and Full-Body Biomechanics During Unconstrained Locomotion
Authors: Prilutsky Boris I. , Sirota Mikhail G. , Gregor Robert J. , Beloozerova Irina N.
Published: May 2005

Recent progress in the understanding of motor cortex function has been achieved primarily by simultaneously recording motor cortex neuron activity and the movement kinematics of the corresponding limb. We have expanded this approach by combining high-quality cortical single-unit activity recordings with synchronized recordings of full-body kinematics and kinetics in the freely behaving cat. The method is illustrated by selected results obtained from two cats tested while walking on a flat surface. Using this method, the activity of 43 pyramidal tract neurons (PTNs) was recorded, averaged over 10 bins of a locomotion cycle, and compared with full-body mechanics by means of principal component and multivariate linear regression analyses. Patterns of 24 PTNs (56%) and 219 biomechanical variables (73%) were classified into just four groups of inter-correlated variables that accounted for 91% of the total variance, indicating that many of the recorded variables had similar patterns. The ensemble activity of different groups of two to eight PTNs accurately predicted the 10-bin patterns of all biomechanical variables (neural decoding) and vice versa; different small groups of mechanical variables accurately predicted the 10-bin pattern of each PTN (neural encoding). We conclude that comparison of motor cortex activity with full-body biomechanics may be a useful tool in further elucidating the function of the motor cortex.
Spatial Distribution of Suppressive Signals Outside the Classical Receptive Field in Lateral Geniculate Nucleus
Authors: Webb Ben S. , Tinsley Christopher J. , Vincent Christopher J. , Derrington Andrew M.
Published: May 2005

A suppressive surround modulates the responsiveness of cells in the lateral geniculate nucleus (LGN), but we know nothing of its spatial structure or the way in which it combines signals arising from different locations. It is generally assumed that suppressive signals are either uniformly distributed or balanced in opposing regions outside the receptive field. Here, we examine the spatial distribution and summation of suppressive signals outside the receptive field in extracellular recordings from 46 LGN cells in anesthetized marmosets. The receptive field of each cell was stimulated with a drifting sinusoidal grating of the preferred size and spatial and temporal frequency; we probed different positions in the suppressive surround with either a large half-annular grating or a small circular grating patch of the preferred spatial and temporal frequency. In many of the cells with a strong suppressive surround (29/46), the spatial distribution of suppression showed clear deviation from circular symmetry. In the majority of these of cells, suppressive signals were spatially asymmetrical or balanced in opposing areas outside the receptive field. A suppressive area was larger than the classical receptive field itself and spatial summation within and between these areas was nonlinear. There was no bias for suppression to arise from foveal or nasal retina where cone density is higher and no other sign of a systematic spatial organization to the suppressive surround. We conclude that nonclassical suppressive signals in LGN deviate from circular symmetry and are nonlinearly combined.
Genomic organization, expression, and function of bitter taste receptors (T2R) in mouse and rat
Authors: Wu S. Vincent , Chen Monica C. , Rozengurt Enrique
Published: May 2005

Mammalian type 2 taste receptors (T2R) are a family of G protein-coupled receptors that mediate bitter signals in taste cells. In the present study, we compared the genomic organization of rodent T2R genes based on the recently completed mouse and rat genomes and examined tissue- and cell-specific expression of T2Rs. Both mouse and rat T2R families consist of 36 intact genes and at least 7 pseudogenes that are mapped to mouse chromosomes 15, 2, and 6 and to rat chromosomes 2, 3, and 4, respectively. All but two T2R genes are clustered on mouse chromosome 6 and rat chromosome 4 with virtually identical genomic organization. The orthologs of the first human T2R gene identified, mT2R119 and rT2R1, are located on mouse chromosome 15 and rat chromosome 2, whereas the novel rodent-specific T2R genes, mT2R134 and rT2R34, are located on mouse chromosome 2 and rat chromosome 3, respectively. Our results, using RT-PCR, demonstrate the presence of transcripts corresponding to the putative denatonium benzoate (DB) and phenylthiocarbamide (PTC) receptors in the antrum, fundus, and duodenum as well as in STC-1 and AR42J cells. The novel rodent-specific T2R gene (mT2R134 and rT2R34) was also expressed in these tissues and cell lines. The addition of DB, PTC, or cycloheximide to AR42J cells induced a rapid increase in the intracellular Ca2+ concentration. The specificity of these effects is shown by the fact that these bitter stimuli did not induce any detectable Ca2+ signaling in many other rodent or human cells that do not express receptors or G proteins implicated in bitter taste signaling. These results demonstrate that mouse and rat T2R genes are highly conserved in terms of genomic organization and tissue expression, suggesting that rodent T2Rs are evolved under similar dietary pressure and share bitter sensing functions in the lingual and gastrointestinal systems.
Stimulation of Paracrine Pathways With Growth Factors Enhances Embryonic Stem Cell Engraftment and Host-Specific Differentiation in the Heart After Ischemic Myocardial Injury
Authors: Kofidis Theo , de Bruin Jorg L. , Yamane Toshiyuki , Tanaka Masashi , Lebl Darren R. , Swijnenburg Rutger-Jan , Weissman Irving L. , Robbins Robert C.
Published: May 2005

Background—

Growth factors play an essential role in organogenesis. We examine the potential of growth factors to enhance cell engraftment and differentiation and to promote functional improvement after transfer of undifferentiated embryonic stem cells into the injured heart.

Methods and Results—

Green fluorescent protein (GFP)–positive embryonic stem cells derived from 129sv mice were injected into the ischemic area after left anterior descending artery ligation in allogenic (BALB/c) mice. Fifty nanograms of recombinant mouse vascular endothelial growth factor, fibroblast growth factor (FGF), and transforming growth factor (TGF) was added to the cell suspension. Separate control groups were formed in which only the growth factors were given. Echocardiography was performed 2 weeks later to evaluate heart function (fractional shortening [FS]), end-diastolic diameter, and left ventricular wall thickness). Hearts were harvested for histology (connexin 43, α-sarcomeric actin, CD3, CD11c, major histocompatability complex class I, hematoxylin-eosin). Degree of restoration (GFP-positive graft/infarct area ratio), expression of cardiac markers, host response, and tumorigenicity were evaluated. Cell transfer resulted in improved cardiac function. TGF-β led to better restorative effect and a stronger expression of connexin 43, α-sarcomeric actin, and major histocompatability complex class I. TGF-β and FGF retained left ventricular diameter. FS was better in the TGF-β, FGF, and embryonic stem cells-only group compared with left anterior descending artery-ligated controls. Growth factors with cells (TGF-β, FGF) resulted in higher FS and smaller end-diastolic diameter than growth factors alone.

Conclusions—

Growth factors can promote in vivo organ-specific differentiation of early embryonic stem cells and improve myocardial function after cell transfer into an area of ischemic lesion. TGF-β should be considered as an adjuvant for myocardial restoration with the use of embryonic stem cells.
Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus
Authors: Langenfeld M.R. , Forst T. , Hohberg C. , Kann P. , Lübben G. , Konrad T. , Füllert S.D. , Sachara C. , Pfützner A.
Published: May 2005

Background—

Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness (IMT) is a strong predictor of myocardial infarction and stroke.

Methods and Results—

We compared the effects of pioglitazone-based therapy (45 mg/d) and glimepiride-based treatment (2.7±1.6 mg/d) for 12 and 24 weeks on metabolic control (HbA
1c
), insulin resistance (homeostasis model assessment), and carotid IMT (B-mode ultrasonography) in a randomized controlled study in 173 orally treated patients with type 2 diabetes (66 women, 107 men; mean±SD age, 62.6±7.9 years; body mass index, 31.8±4.6 kg/m
2
; HbA
1c
, 7.5±0.9%). Treatment was generally well tolerated in both groups. Despite similar improvements in metabolic control (HbA
1c
) after 24 weeks (−0.8±0.9% [pioglitazone] versus −0.6±0.8% [glimepiride];
P
=NS), carotid IMT was reduced only in the pioglitazone group after 12 weeks (−0.033±0.052 versus −0.002±0.047 mm [glimepiride];
P
<0.01 between groups) and 24 weeks (−0.054±0.059 versus −0.011±0.058 mm [glimepiride];
P
<0.005 between groups). Insulin resistance was also improved only in the pioglitazone group (homeostasis model assessment, −2.2±3.4 versus −0.3±3.3;
P
<0.0001 between groups). Reduction of IMT correlated with improvement in insulin resistance (
r
=0.29,
P
<0.0005) and was independent of improvement in glycemic control (
r
=0.03,
P
=0.68).

Conclusions—

We found a substantial regression of carotid IMT, independent of improved glycemic control, after 12 and 24 weeks of pioglitazone treatment. This finding may have important prognostic implications for patients with type 2 diabetes mellitus.
Angiotensin II Activates the Smad Pathway in Vascular Smooth Muscle Cells by a Transforming Growth Factor-β–Independent Mechanism
Authors: Rodríguez-Vita Juan , Sánchez-López Elsa , Esteban Vanesa , Rupérez Mónica , Egido Jesús , Ruiz-Ortega Marta
Published: May 2005

Background—

Angiotensin II (Ang II) participates in vascular fibrosis. Transforming growth factor-β (TGF-β) is considered the most important fibrotic factor, and Smad proteins are essential components of the TGF-β signaling system. Our aim was to investigate whether Ang II activates the Smad pathway in vascular cells and its potential role in fibrosis, evaluating connective tissue growth factor (CTGF) and extracellular matrix (ECM) proteins.

Methods and Results—

Systemic infusion of Ang II into Wistar rats increased aortic Smad2, phosphorylated-Smad2, and Smad4 expression, associated with CTGF upregulation. In growth-arrested vascular smooth muscle cells, Ang II treatment for 20 minutes caused Smad2 phosphorylation, nuclear translocation of phosphorylated-Smad2 and Smad4, and increased Smad DNA-binding activity. Ang II also caused Smad overexpression and Smad-dependent gene transcription. The AT
1
antagonist losartan diminished Ang II-induced Smad activation. The blockade of endogenous TGF-β did not modify the activation of Smad caused by Ang II. The p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 diminished Ang II-induced Smad2 phosphorylation. These data show that Ang II activates the Smad pathway via AT
1
receptors and MAPK activation independently of TGF-β. Transient transfection with Smad7, which interferes with receptor-mediated activation of Smad2, diminished Ang II-induced CTGF promoter activation, gene and protein expression, and fibronectin and type-1 procollagen overexpression, showing that Smad activation is involved in Ang II-induced fibrosis.

Conclusions—

Our results show that Ang II activates the Smad signaling system in vascular cells in vivo and in vitro. Smad proteins are involved in Ang II-induced CTGF and ECM overexpression independently of TGF-β. This novel finding suggests that Smad activation could be involved in the profibrogenic effects of Ang II in vascular diseases.
Adipose Tissue, Inflammation, and Cardiovascular Disease
Authors: Berg Anders H. , Scherer Philipp E.
Published: May 2005

Mounting evidence highlights the role of adipose tissue in the development of a systemic inflammatory state that contributes to obesity-associated vasculopathy and cardiovascular risk. Circulating mediators of inflammation participate in the mechanisms of vascular insult and atheromatous change, and many of these inflammatory proteins are secreted directly from adipocytes and adipose tissue–derived macrophages. Several factors linking obesity with an increased cardiovascular risk have been identified. The adipocyte-specific secretory protein adiponectin is a particularly promising candidate in this context. Its levels are decreased in obesity. Adiponectin may mediate some of its demonstrated cardioprotective effects through its anti-inflammatory properties. In addition to decreased expression of beneficial adipokines, secretion of a host of inflammatory factors from visceral adipose tissue may contribute to the increased cardiovascular risk associated with obesity. The cardioprotective effects of many of the most popular drug regimens corroborate these conclusions, demonstrating that along with improvements in other therapeutic end points, they mediate improvements in systemic inflammation. In some cases, these improvements are attributable to direct suppression of inflammatory signaling in adipocytes. The targeted suppression of various proinflammatory cascades in adipocytes specifically represents an exciting new therapeutic opportunity for the cardiovascular disease area.
Impaired Vascular Growth in Late Adolescence After Intrauterine Growth Restriction
Authors: Brodszki J. , Länne T. , Maršál K. , Ley D.
Published: May 2005

Background—

Abnormal blood flow in a fetus small for gestational age indicates true fetal intrauterine growth restriction (IUGR). We tested the hypothesis that IUGR with abnormal fetal blood flow is associated with long-term abnormal vascular morphology and function in adolescence.

Methods and Results—

In a prospective study, vascular mechanical properties of the common carotid artery (CCA), abdominal aorta, and popliteal artery (PA) were assessed by echo-tracking sonography in 21 adolescents with IUGR and abnormal fetal aortic blood flow and in 23 adolescents with normal fetal growth and normal fetal aortic blood flow. Endothelium-dependent and -independent vasodilatation of the brachial artery was measured by high-resolution ultrasound. After adjustment for body surface area and sex, the IUGR group had significantly smaller end-diastolic vessel diameters than the referents in the abdominal aorta and PA (mean difference, 1.7 mm [95% CI, 0.62 to 2.74] and 0.6 mm [95% CI, 0.25 to 1.02], respectively) (
P
=0.003 and
P
=0.002, respectively), with a similar trend in the CCA (
P
=0.09). A higher resting heart rate was observed in the IUGR group (
P
=0.01). No differences were found in stiffness or in endothelium-dependent and -independent vasodilatation between the 2 groups.

Conclusions—

IUGR caused by placental insufficiency appears to be associated with impaired vascular growth persisting into young adulthood in both men and women. The smaller aortic dimensions and the higher resting heart rate seen in adolescents with previous IUGR may be of importance for future cardiovascular health.
Diurnal Variations in Lake-Effect Precipitation near the Western Great Lakes
Authors: Kristovich David A. R. , Spinar Michael L.
Published: May 2005

Lake-effect snowstorms are important parts of the climate of the U.S. Upper Midwest, with significant economic and societal impacts on communities close to the Great Lakes. Some impacts, particularly those on air and ground transportation, depend critically on the time of day that lake-effect precipitation occurs. This study utilizes hourly precipitation data collected near Lakes Superior and Michigan to determine the diurnal behavior of lake-effect precipitation frequency. Precipitation data from approximately 200 lake-effect days during 1988–93, identified by a previous study based on visible satellite data, are examined. A distinct morning maximum and afternoon/evening minimum in lake-effect precipitation frequency was observed, with the largest variations at sites within the snowbelt regions. The relative importance of several factors known to influence lake-effect precipitation development was examined to gain insight into the physical mechanisms controlling the diurnal evolution of lake-effect precipitation.
Global Hydroclimatological Teleconnections Resulting from Tropical Deforestation
Authors: Avissar Roni , Werth David
Published: May 2005

Past studies have indicated that deforestation of the Amazon basin would result in an important rainfall decrease in that region but that this process had no significant impact on the global temperature or precipitation and had only local implications. Here it is shown that deforestation of tropical regions significantly affects precipitation at mid- and high latitudes through hydrometeorological teleconnections. In particular, it is found that the deforestation of Amazonia and Central Africa severely reduces rainfall in the lower U.S. Midwest during the spring and summer seasons and in the upper U.S. Midwest during the winter and spring, respectively, when water is crucial for agricultural productivity in these regions. Deforestation of Southeast Asia affects China and the Balkan Peninsula most significantly. On the other hand, the elimination of any of these tropical forests considerably enhances summer rainfall in the southern tip of the Arabian Peninsula. The combined effect of deforestation of these three tropical regions causes a significant decrease in winter precipitation in California and seems to generate a cumulative enhancement of precipitation during the summer in the southern tip of the Arabian Peninsula.
Constraining Land Surface and Atmospheric Parameters of a Locally Coupled Model Using Observational Data
Authors: Liu Yuqiong , Gupta Hoshin V. , Sorooshian Soroosh , Bastidas Luis A. , Shuttleworth William J.
Published: May 2005

In coupled land surface–atmosphere modeling, the possibility and benefits of constraining model parameters using observational data bear investigation. Using the locally coupled NCAR Single-column Community Climate Model (NCAR SCCM), this study demonstrates some feasible, effective approaches to constrain parameter estimates for coupled land–atmosphere models and explores the effects of including both land surface and atmospheric parameters and fluxes/variables in the parameter estimation process, as well as the value of conducting the process in a stepwise manner. The results indicate that the use of both land surface and atmospheric flux variables to construct error criteria can lead to better-constrained parameter sets. The model with “optimal” parameters generally performs better than when a priori parameters are used, especially when some atmospheric parameters are included in the parameter estimation process. The overall conclusion is that, to achieve balanced, reasonable model performance on all variables, it is desirable to optimize both land surface and atmospheric parameters and use both land surface and atmospheric fluxes/variables for error criteria in the optimization process. The results also show that, for a coupled land–atmosphere model, there are potential advantages to using a stepwise procedure in which the land surface parameters are first identified in offline mode, after which the atmospheric parameters are determined in coupled mode. This stepwise scheme appears to provide comparable solutions to a fully coupled approach, but with considerably reduced computational time. The trade-off in the ability of a model to satisfactorily simulate different processes simultaneously, as observed in most multicriteria studies, is most evident for sensible heat and precipitation in this study for the NCAR SCCM.
A Method for Evaluating the Accuracy of Quantitative Precipitation Estimates from a Hydrologic Modeling Perspective
Authors: Gourley Jonathan J. , Vieux Baxter E.
Published: May 2005

A major goal in quantitative precipitation estimation and forecasting is the ability to provide accurate initial conditions for the purposes of hydrologic modeling. The accuracy of a streamflow prediction system is dependent upon how well the initial hydrometeorological states are characterized. A methodology is developed to objectively and quantitatively evaluate the skill of several different precipitation algorithms at the scale of application—a watershed. Thousands of hydrologic simulations are performed in an ensemble fashion, enabling an exploration of the model parameter space. Probabilistic statistics are then utilized to compare the relative skill of hydrologic simulations produced from the different precipitation inputs to the observed streamflow. The primary focus of this study is to demonstrate a methodology to evaluate precipitation algorithms that can be used to supplement traditional radar–rain gauge analyses. This approach is appropriate for the evaluation of precipitation estimates or forecasts that are intended to serve as inputs to hydrologic models.