bluuebunny/crossref_metadata_2025 huggingface dataset:
Nitrogen fixation associated with 'Park' Kentucky bluegrass (Poapratensis L.)
Authors: Shearman R. C. , Pedersen W. L. , Klucas R. V. , Kinbacher E. J.
Published: April 2010

Associative nitrogen fixation in Kentucky bluegrass (Poa pratensis L.) turfs inoculated with five nitrogen-fixing bacterial isolates was evaluated using the acetylene reduction assay and nitrogen accumulation as indicators of fixation. 'Park' and 'Nugget' Kentucky bluegrass turfs were grown in controlled environment chambers and inoculated with Klebsiella pneumoniae (W-2, W-6, and W-14), Erwinia herbicola (W-8), and Enterobacter cloacae (W-11). 'Park' inoculated with K. pneumoniae (W-6) had significant acetylene reduction activity using undisturbed turfs. Other treatments including turfs treated with heat-killed cells had no significant difference in acetylene reduction. In a second study, 'Park' and 'South Dakota Certified' turfs were grown in a greenhouse and inoculated with K. pneumoniae (W-6) and E. herbicola (W-8). 'Park' inoculated with K. pneumoniae (W-6) had increased acetylene reduction activity rates and also a greater nitrogen accumulation in aerial tissues when compared to controls. Acetylene reduction activity was correlated (r = 0.92) to nitrogen accumulation. Other treatments did not effectively increase acetylene reduction activity or nitrogen accumulation.
Measurement of antibodies to rabies virus by immunoelectron microscopy
Authors: Chaudhary R. K. , Cho H. C. , Monette M. T.
Published: April 2010

Immunoelectron microscopy (IEM) was used to measure rabies antibodies in 47 serum samples from vaccinees with results similar to those obtained by mouse neutralization test (MNT). The use of inactivated rabies virus for IEM eliminated the hazard associated with live virus used in the MNT.
Release of β-glucuronidase from peritoneal macrophages of normal and endotoxin-tolerant mice
Authors: Snyder Stephen L. , Eklund Sharyn K. , Walker Richard I.
Published: April 2010

Lysosomal enzyme release from cells involved in inflammatory response could play a central role in the pathogenesis of endotoxin shock. Therefore we have studied the release of the lysosomal enzyme, β-glucuronidase, from peritoneal macrophages obtained from normal and endotoxin-tolerant B6CBF1 mice both before and after challenge with lethal doses of endotoxin. Unstimulated cells from tolerant mice spontaneously released a smaller percentage of their total β-glucuronidase content in culture than cells from normal mice during a 5-h incubation period. In support of the lysosomal enzyme release hypothesis, it was found that the in vitro release of β-glucuronidase was accelerated when cells were collected from the mouse peritoneum 3 h after i.v. challenge with a lethal dose (1.0 mg) of endotoxin. The increased in vitro "leakiness" of peritoneal macrophages following endotoxin challenge was less marked when tolerance was induced in mice by prior repeated injections of endotoxin. Furthermore, measurements of the total enzyme activities of peritoneal cells revealed a significant reduction in the β-glucuronidase content of cells from normal mice 3 h after endotoxin challenge but no such decrease for cells from tolerant mice. These results suggest that macrophages in endotoxin-sensitive mice release their lysosomal enzymes in vivo during endotoxemia, whereas cells found in tolerant mice do not.In related experiments, the phagocytosis of latex particles and inhibition of bacterial growth by macrophages from normal and tolerant mice were compared. These studies suggest that cells from tolerant mice may also release a smaller percentage of their lysosomal enzymes during phagocytosis.
Thiocyanate utilization by an Arthrobacter
Authors: Betts P. M. , Rinder D. F. , Fleeker J. R.
Published: April 2010

An Arthrobacter species, which utilized thiocyanate (SCN−) as a nitrogen source, was isolated from soil by the enrichment culture method. The organism tolerated SCN− concentrations up to 0.1 M. On addition of nitrate or ammonium ion to cultures of the isolate growing in the presence of SCN−, the organism continued to degrade SCN−. Degradation could be followed by release of 14CO2 from SCN−(14C). The SCN−-degrading activity diminished to low levels as the stationary phase of growth was approached.
Un nouveau serotype de Salmonella isole au Canada: Salmonella Sherbrooke (16:d:1,6)
Authors: Gosselin F. M. , Basu A. K. , Caprioli T. M. , Kasatiya S. S.
Published: April 2010

A new Salmonella serotype classified in the Kauffman sub-genus I (Kauffman 1963) has been isolated in Canada from a stock of cacao beans from Nigeria. Salmonella sherbrooke shares the antigenic structure 16:d:1,6. [Translated by the journal]
Sulfur isotope fractionation by Salmonella heidelberg: inverse isotope effects during growth on high concentrations of Na2SO3
Authors: McCready R. G. L. , Krouse H. R.
Published: April 2010

During growth on minimal salts – glucose media supplemented with high concentrations of Na2SO3 (10−3 and 10−2 M), Salmonella heidelberg exhibited cytological and growth responses which indicated increased cellular toxicity with increasing sulfite concentrations. The large quantities of sulfide evolved during growth at both SO32− concentrations were accompanied by large normal and inverse isotope effects. Consistent with earlier findings, this organism was found capable of rapidly metabolizing both the sulfane and sulfonate sulfur of thiosulfate. Therefore, the isotope effects do not appear to be caused by extracellular chemical thiosulfate formation.
The effect of changes in pH on phosphate and potassium uptake by Monascus rubiginosus ATCC 16367 in submerged shaken culture
Authors: Carels Mariette , Shepherd David
Published: April 2010

Monascus rubiginosus ATCC 16367 was cultivated aerobically in media containing ammonium and nitrate as nitrogen source. The pH of the medium was adjusted at different times, the pH of the nitrate medium being lowered to the pH of the ammonium medium and the pH of the ammonium medium raised to that of the nitrate. More phosphate was taken up on the nitrate medium, but potassium uptake did not start until 24 h. On the ammonium medium, both were taken up in parallel from the beginning, but the amount of phosphate taken up never reached the same level as on nitrate medium. When the pH was adjusted, the uptakes changed, especially on the ammonium medium where a great increase in phosphate uptake was observed. More conidia were formed on the nitrate medium and more pigment on the ammonium medium. When the pH of either media was adjusted, the development of conidia and pigment production changed to that of the other control medium where the pH evolved normally in the direction of the change, regardless of the source of nitrogen. The reasons for the development of conidia on nitrate medium or where the pH is high, and the production of pigment on ammonium medium or at low pH is discussed.
ON THE DIFFERENCE BETWEEN OPTIMAL COMBINATION FUNCTIONS FOR VERIFICATION AND IDENTIFICATION SYSTEMS
Authors: TULYAKOV SERGEY , WU CHAOHONG , GOVINDARAJU VENU
Published: April 2010

We have investigated different scenarios of combining pattern matchers. The combination problem can be viewed as a construction of a postprocessing classifier operating on the matching scores of the combined matchers. The optimal combination algorithm for verification systems corresponds to the likelihood ratio combination function. It can be implemented by the direct reconstruction of this function with genuine and impostor score density approximations. However, the optimal combination algorithm for identification systems is difficult to express analytically. We will show that this difficulty is caused by the dependencies between matching scores assigned to different classes by the same classifier. The experiments on the large sets of scores from handwritten word recognizers operating on postal images and biometric matchers (NIST biometric score set BSSR1) confirm the existence of such dependencies and that the optimal combination functions for verification and identification systems are different.
DEHN SURGERY ALONG TORUS LINKS
Authors: KADOKAMI TERUHISA , SHIMOZAWA MASAFUMI
Published: April 2010

We determine Dehn surgery along torus links by using Rolfsen moves and the classification theorem of Seifert fibered spaces over S2.
BRAID GROUP REPRESENTATIONS ARISING FROM THE YANG–BAXTER EQUATION
Authors: FRANKO JENNIFER M.
Published: April 2010

This paper aims to determine the images of the braid group under representations afforded by the Yang–Baxter equation when the solution is a non-trivial 4 × 4 matrix. Making the assumption that all the eigenvalues of the Yang–Baxter solution are roots of unity, leads to the conclusion that all the images are finite.

Using results of Turaev, we have also identified cases in which one would get a link invariant. Finally, by observing the group algebra generated by the image of the braid group sometimes factor through known algebras, in certain instances we can identify the invariant as particular specializations of a known invariant.
Booming Sand Dunes
Authors: Hunt Melany L. , Vriend Nathalie M.
Published: April 2010

“Booming” sand dunes have a remarkable capacity to produce sounds that are comparable with those from a stringed instrument. This phenomenon, in which sound is generated after an avalanching of sand along the slip face of a dune, has been known for centuries and occurs in at least 40 sites around the world. A spectral analysis of the sound shows a dominant frequency between 70 and 110 Hz, as well as higher harmonics. Depending on the location and time of year, the sound may continue for several minutes, even after the avalanching of sand has ceased. This review presents historical observations and explanations of the sound, many of which contain accurate and insightful descriptions of the phenomenon. In addition, the review describes recent work that provides a scientific explanation for this natural mystery, which is caused by sound resonating in a surface layer of the dune.
Nature and Climate Effects of Individual Tropospheric Aerosol Particles
Authors: Pósfai Mihály , Buseck Peter R.
Published: April 2010

Aerosol particles in the atmosphere exert a strong influence on climate by interacting with sunlight and by initiating cloud formation. Because the tropospheric aerosol is a heterogeneous mixture of various particle types, its climate effects can only be fully understood through detailed knowledge of the physical and chemical properties of individual particles. Here we review the results of individual-particle studies that use microscopy-based techniques, emphasizing transmission electron microscopy and focusing on achievements of the past ten years. We discuss the techniques that are best suited for studying distinct particle properties and provide a brief overview of major particle types, their identification, and their sources. The majority of this review is concerned with the optical properties and hygroscopic behavior of aerosol particles; we discuss recent results and highlight the potential of emerging microscopy techniques for analyzing the particle properties that contribute most to climate effects.
Gene ablation for PEPT1 in mice abolishes the effects of dipeptides on small intestinal fluid absorption, short-circuit current, and intracellular pH
Authors: Chen Mingmin , Singh Anurag , Xiao Fang , Dringenberg Ulrike , Wang Jian , Engelhardt Regina , Yeruva Sunil , Rubio-Aliaga Isabel , Näßl Anna-Maria , Kottra Gabor , Daniel Hannelore , Seidler Ursula
Published: April 2010

PEPT1 function in mouse intestine has not been assessed by means of electrophysiology and methods to assess its role in intracellular pH and fluid homeostasis. Therefore, the effects of the dipeptide glycilsarcosin (Gly-Sar) on jejunal fluid absorption and villous enterocyte intracellular pH (pHi) in vivo, as well as on enterocyte[14C]Gly-Sar uptake, short-circuit current ( Isc) response, and enterocyte pHiin vitro were determined in wild-type and PEPT1-deficient mice and in mice lacking PEPT1. Immunohistochemistry for PEPT1 failed to detect any protein in enterocyte apical membranes in Slc15a1−/−animals. Saturable Gly-Sar uptake in Slc15a1−/−everted sac preparations was no longer detectable. Similarly, Gly-Sar-induced jejunal Iscresponse in vitro was abolished. The dipeptide-induced increase in fluid absorption in vivo was also abolished in animals lacking PEPT1. Since PEPT1 acts as an acid loader in enterocytes, enterocyte pHiwas measured in vivo by two-photon microscopy in SNARF-4-loaded villous enterocytes of exteriorized jejuni in anesthetized mice, as well as in BCECF-loaded enterocytes of microdissected jejunal villi. Gly-Sar-induced pHidecrease was no longer observed in the absence of PEPT1. A reversal of the proton gradient across the luminal membrane did not significantly diminish Gly-Sar-induced Iscresponse, whereas a depolarization of the apical membrane potential by high K+or via Na+-K+-ATPase inhibition strongly diminished Gly-Sar-induced Iscresponses. This study demonstrates for the first time that proton-coupled electrogenic dipeptide uptake in the native small intestine, mediated by PEPT1, relies on the negative apical membrane potential as the major driving force and contributes significantly to intestinal fluid transport.
Proteomic analysis of epicardial and subcutaneous adipose tissue reveals differences in proteins involved in oxidative stress
Authors: Salgado-Somoza Antonio , Teijeira-Fernández Elvis , Fernández Ángel Luis , González-Juanatey José Ramón , Eiras Sonia
Published: May 2010

Epicardial adipose tissue (EAT) is an endocrine organ adjacent to coronary arteries and myocardium without anatomy barriers. Locally produced adipokines may reflect or affect to cardiovascular physiology and pathology. Our aim was to study the protein expression profiles of EAT and subcutaneous adipose tissue (SAT) to identify local candidate molecules characterizing EAT in patients with cardiovascular disease. EAT and SAT samples were collected from 55 patients undergoing heart surgery. Proteins from these tissues were separated by two-dimensional (2D) gel electrophoresis, and differences between them were identified by MALDI-TOF/TOF spectra. Differences in protein levels were further investigated by real-time RT-PCR and Western blots, and production of reactive oxygen species (ROS) in EAT and SAT was evaluated by nitroblue tetrazolium chloride assays. ROS production was higher in EAT than SAT. We have found mRNA differences for catalase, glutathione S-transferase P, and protein disulfide isomerase, and 2D Western blots additionally showed post-translational differences for phosphoglycerate mutase 1; all four are related to oxidative stress pathways. EAT suffers greater oxidative stress than SAT in patients with cardiovascular diseases and exhibits associated proteomic differences that suggest the possibility of its association with myocardial stress in these patients.
Analysis of responses to the Rho-kinase inhibitor Y-27632 in the pulmonary and systemic vascular bed of the rat
Authors: Casey David B. , Badejo Adeleke M. , Dhaliwal Jasdeep S. , Sikora James L. , Fokin Alex , Golwala Neel H. , Greco Anthony J. , Murthy Subramanyam N. , Nossaman Bobby D. , Hyman Albert L. , Kadowitz Philip J.
Published: May 2010

Responses to the Rho kinase inhibitor Y-27632 were investigated in the anesthetized rat. Under baseline conditions intravenous injections of Y-27632 decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressures were enhanced when baseline tone was increased with U-46619, and under elevated tone conditions Y-27632 produced similar percent decreases in pulmonary and systemic arterial pressures. Injections of Y-27632 prevented and reversed the hypoxic pulmonary vasoconstrictor response. The increase in pulmonary arterial pressure in response to ventilation with a 10% O2-90% N2gas mixture was not well maintained during the period of hypoxic exposure. Treatment with the nitric oxide (NO) synthase (NOS) inhibitor nitro-l-arginine methyl ester (l-NAME) increased pulmonary arterial pressure and prevented the decline or fade in the hypoxic pulmonary vasoconstrictor response. The hypoxic pulmonary vasoconstrictor response was reversed by Y-27632 in control and in l-NAME-treated animals. The Rho kinase inhibitor attenuated increases in pulmonary arterial pressures in response to intravenous injections of serotonin, angiotensin II, and Bay K 8644. Y-27632, sodium nitrite, and BAY 41-8543, a guanylate cyclase stimulator, decreased pulmonary and systemic arterial pressures and vascular resistances in monocrotaline-treated rats. These data suggest that Rho kinase is involved in the regulation of baseline tone and in the mediation of pulmonary vasoconstrictor responses. The present data suggest that the hypoxic pulmonary vasoconstrictor response is modulated by the release of NO that mediates the nonsustained component of the response in the anesthetized rat. These data suggest that Rho kinase and NOS play important roles in the regulation of vasoconstrictor tone in physiological and pathophysiological states and that monocrotaline-induced pulmonary hypertension can be reversed by agents that inhibit Rho kinase, generate NO, or stimulate soluble guanylate cyclase.
Time-dependent action of carbon monoxide on the newborn cerebrovascular circulation
Authors: Knecht Kenneth R. , Milam Sarah , Wilkinson Daniel A. , Fedinec Alexander L. , Leffler Charles W.
Published: May 2010

Carbon monoxide (CO) causes cerebral arteriolar dilation in newborn pigs by the activation of large-conductance Ca2+-activated K+ channels. In adult rat cerebral and skeletal muscle arterioles, CO has been reported to produce constriction caused by the inhibition of nitric oxide (NO) synthase (NOS). We hypothesized that, in contrast to dilation to acute CO, more prolonged exposure of newborn cerebral arterioles to elevated CO produces constriction by reducing NO. In piglets with closed cranial windows, pial arteriolar responses to isoproterenol (10−6 M), sodium nitroprusside (SNP; 10−7 and 3 × 10−7 M), and l-arginine ethyl ester (l-Arg; 10−5 and 10−4 M) were determined before and after 2 h of treatment with CO. CO (10−7 M) caused transient dilation and had no further effects. CO (2 × 10−7 and 10−6 M) initially caused vasodilation, but over the 2-h exposure, pial arterioles constricted and removal of the CO caused dilation. Exposure to elevated CO (2 h) did not alter dilation to SNP or isoproterenol. Conversely, the NOS substrate l-Arg caused dilation before CO that was progressively lost over 90 min of elevated CO. If NO was held constant, CO caused dilation that was sustained for 2 h. We conclude that in neonates, cerebral arteriole responses to CO are biphasic: dilation to acute elevation with subsequent constriction from NOS inhibition after more prolonged exposure. As a result, short episodic production of CO allows function as a dilator gasotransmitter, whereas prolonged elevation can reduce NO to elevate cerebrovascular tone. The interaction between heme oxygenase/CO and NOS/NO could form a negative feedback system in the control of cerebral vascular tone.
Mitochondrial KATPchannel inhibition blunts arrhythmia protection in ischemic exercised hearts
Authors: Quindry John C. , Schreiber Lindsey , Hosick Peter , Wrieden Jenna , Irwin J. Megan , Hoyt Emily
Published: May 2010

The mechanisms responsible for anti-arrhythmic protection during ischemia-reperfusion (IR) in exercised hearts are not fully understood. The purpose of this investigation was to examine whether the ATP-sensitive potassium channels in the mitochondria (mito KATP) and sarcolemma (sarc KATP) provide anti-arrhythmic protection in exercised hearts during IR. Male Sprague-Dawley rats were randomly assigned to cardioprotective treadmill exercise or sedentary conditions before IR (I = 20 min, R = 30 min) in vivo. Subsets of exercised animals received pharmacological inhibitors for mito KATP(5-hydroxydecanoate) or sarc KATP(HMR1098) before IR. Blinded analysis of digital ECG tracings revealed that mito KATPinhibition blunted the anti-arrhythmic effects of exercise, while sarc KATPinhibition did not. Endogenous antioxidant enzyme activities for total, CuZn, and Mn superoxide dismutase, catalase, and glutathione peroxidase from ischemic and perfused ventricular tissue were not mitigated by IR, although oxidative stress was elevated in sedentary and mito KATP-inhibited hearts from exercised animals. These findings suggest that the mito KATPchannel provides anti-arrhythmic protection as part of exercise-mediated cardioprotection against IR. Furthermore, these data suggest that the observed anti-arrhythmic protection may be associated with preservation of redox balance in exercised hearts.
S1P2 receptor-dependent Rho-kinase activation mediates vasoconstriction in the murine pulmonary circulation induced by sphingosine 1-phosphate
Authors: Szczepaniak William S. , Pitt Bruce R. , McVerry Bryan J.
Published: May 2010

Vasoactive properties of sphingosine 1-phosphate (S1P) have been demonstrated by many investigators to vary in systemic vascular beds. These variations appear to reflect differential S1P receptor expression in the vasculature of these tissues. Although S1P has been demonstrated to enhance endothelial barrier function, induce airway hyperresponsiveness, and modulate immune responses in the lung, the pulmonary vasomotor effects of S1P remain poorly defined. In the present study, we sought to define the vasoregulatory effects of S1P in the pulmonary vasculature and to elucidate the underlying mechanisms operative in effecting the response in the intact lung. S1P (10 μM) increased pulmonary vascular resistance (PVR) by 36% in the isolated perfused mouse lung. S1P-induced vasoconstriction was reduced by 64% by concomitant administration of the Rho-kinase inhibitor Y27632 (10 μM). Similarly, the S1P response was attenuated by >50% after S1P2 receptor antagonism (JTE-013; 10 μM) and in S1P2 receptor null mice. In contrast, S1P3 receptor antagonism (VPC23019; 10 μM) had no effect on the contractile response to S1P. Furthermore, we confirmed the role of Rho-kinase as an important regulator of basal vasomotor tone in the isolated perfused mouse lung. These results suggest that S1P is capable of altering pulmonary vascular tone in vivo and may play an important role in the modulation of pulmonary vascular tone both in the normal lung and under pathological conditions.
Diesel exhaust particles override natural injury-limiting pathways in the lung
Authors: Chaudhuri N. , Paiva C. , Donaldson K. , Duffin R. , Parker L. C. , Sabroe I.
Published: May 2010

Induction of effective inflammation in the lung in response to environmental and microbial stimuli is dependent on cooperative signaling between leukocytes and lung tissue cells. We explored how these inflammatory networks are modulated by diesel exhaust particles (DEP) using cocultures of human monocytes with epithelial cells. Cocultures, or monoculture controls, were treated with DEP in the presence or absence of LPS or flagellin. Production of cytokines was explored by Western blotting and ELISA; cell signaling was analyzed by Western blotting. Here, we show that responses of epithelial cells to DEP are amplified by the presence of monocytes. DEP amplified the responses of cellular cocultures to very low doses of TLR agonists. In addition, in the presence of DEP, the responses induced by LPS or flagellin were less amenable to antagonism by the physiological IL-1 antagonist, IL-1ra. This was paralleled by the uncoupling of IL-1 production and release from monocytes, potentially attributable to an ability of DEP to sequester or degrade extracellular ATP. These data describe a model of inflammation where DEP amplifies responses to low concentrations of microbial agonists and alters the nature of the inflammatory milieu induced by TLR agonists.
Can lineage-specific markers be identified to characterize mesenchyme-derived cell populations in the human airways?
Authors: Singh Shailendra R. , Billington Charlotte K. , Sayers Ian , Hall Ian P.
Published: May 2010

Mesenchyme-derived cells in the airway wall including airway smooth muscle cells, fibroblasts, and myofibroblasts are known to play important roles in airway remodeling. The lack of specific phenotypical markers makes it difficult to define these cell populations in primary cultures. Most relevant studies to date have used animal airway tissues, vascular tissues, or transformed cell lines with only limited studies attempting to phenotypically characterize human airway mesenchymal cells. The objectives of this study were to evaluate reported markers and identify novel markers to define these cell types. We could not identify any specific marker to define these cell populations in vitro that permitted unequivocal identification using immunocytochemistry. However, characteristic filamentous α-smooth muscle actin distribution was observed in a significant (∼25%) proportion of human airway smooth muscle cells, whereas this was not observed in airway fibroblasts. A significantly higher proportion of airway fibroblasts expressed α1- and α2-integrin receptors compared with human airway smooth muscle cells as assessed by fluorescence activated cell sorting. Global gene expression profiling identified aldo-keto reductase 1C3 (AKR1C3) and cathepsin K as being novel markers to define airway smooth muscle cells, whereas integrin-α8(ITGA8) and thromboxane synthase 1 (TBXAS1) were identified as novel airway fibroblast-specific markers, and these findings were validated by RT-PCR. Ex vivo studies in human airway tissue sections identified high-molecular weight caldesmon and α-smooth muscle actin as being expressed in smooth muscle bundles, whereas ITGA8 and TBXAS1 were absent from these.
α1GT-type calcium channel selectively regulates P-selectin surface expression in pulmonary capillary endothelium
Authors: Zhou Chun , Chen Hairu , King Judy A. , Sellak Hassan , Kuebler Wolfgang M. , Yin Jun , Townsley Mary I. , Shin Hee-Sup , Wu Songwei
Published: May 2010

Regulated P-selectin surface expression provides a rapid measure for endothelial transition to a proinflammatory phenotype. In general, P-selectin surface expression results from Weibel-Palade body (WPb) exocytosis. Yet, it is unclear whether pulmonary capillary endothelium possesses WPbs or regulated P-selectin surface expression and, if so, how inflammatory stimuli initiate exocytosis. We used immunohistochemistry, immunofluorescence labeling, ultrastructural assessment, and an isolated perfused lung model to demonstrate that capillary endothelium lacks WPbs but possesses P-selectin. Thrombin stimulated P-selectin surface expression in both extra-alveolar vessel and alveolar capillary endothelium. Only in capillaries was the thrombin-stimulated P-selectin surface expression considerably mitigated by pharmacologic blockade of the T-type channel or genetic knockout of the T-type channel α1G-subunit. Depolarization of endothelial plasma membrane via high K+perfusion capable of eliciting cytosolic Ca2+transients also provoked P-selectin surface expression in alveolar capillaries that was abolished by T-type channel blockade or α1Gknockout. Our findings reveal an intracellular WPb-independent P-selectin pool in pulmonary capillary endothelium, where the regulated P-selectin surface expression is triggered by Ca2+transients evoked through activation of the α1GT-type channel.
Effects of Adrenomedullin on the Glomerular Adrenomedullin System in a Rat Model of Anti-Thy1 Glomerulonephritis
Authors: Geissler Bettina , Plank Christian , Hartner Andrea , Amann Kerstin , Struwe Friedrich G. , Hilgers Karl F. , Rascher Wolfgang , Dötsch Jörg
Published: April 2010

Background: Adrenomedullin (ADM) has antiproliferative effects on glomerular mesangial cells. The study was performed to determine changes in glomerular gene expression of the ADM system by ADM treatment in anti-Thy1 glomerulonephritis (GN). Methods: GN in rats was induced by injecting anti-Thy-1 antibody. To show the effect of ADM treatment, rats received ADM from day 3 to day 6 of GN. Supplemental rats were sacrificed on day 3, 7 and 14 of GN to show the expression pattern of adrenomedullin and its receptors. Glomeruli were prepared by sieving or laser-assisted microdissection. Expression of ADM, calcitonin receptor-like receptor (CLR), receptor activity-modifying proteins (RAMP) 1–3, CD34, Thy1 and nephrin was analyzed using real-time PCR. Results: During GN a reduction of CLR and RAMP 2 + 3 expressions was detected on days 3, 7 and 14, while RAMP 1 rose. ADM mRNA decreased on days 3 and 7. Thy1 expression as a surrogate of mesangial cell number was downregulated during GN. A significant reduction of CD34 expression, as a surrogate for endothelial cell number, was detected on day 7. A tendency towards reduction of nephrin gene expression, as a surrogate for number of podocytes, was seen. The administration of ADM during GN did not change the expression on Thy1, CD34 or nephrin. The results were similar for microdissected and sieved glomeruli. In ADM-treated GN animals ADM gene expression rose compared to untreated GN animals on day 6. These effects were detected both in sieved and microdissected glomeruli. ADM administration did not change the expression of the receptors. Conclusion: The downregulation of adrenomedullin during GN at the gene level can be improved by ADM application.
Nexframe Frameless Stereotaxy with Multitract Microrecording: Accuracy Evaluated by Frame-Based Stereotactic X-Ray
Authors: Fukaya Chikashi , Sumi Koichiro , Otaka Toshiharu , Obuchi Toshiki , Kano Toshikazu , Kobayashi Kazutaka , Oshima Hideki , Yamamoto Takamitsu , Katayama Yoichi
Published: April 2010

Objective: The development of image-guided systems rendered it possible to perform frameless stereotactic surgery for deep brain stimulation (DBS). As well as stereotactic targeting, neurophysiological identification of the target is important. Multitract microrecording is an effective technique to identify the best placement of an electrode. This is a report of our experience of using the Nexframe frameless stereotaxy with Ben’s Gun multitract microrecording drive and our study of the accuracy, usefulness and disadvantages of the system. Methods: Five patients scheduled to undergo bilateral subthalamic nucleus (STN) DBS were examined. The Nexframe device was adjusted to the planned target, and electrodes were introduced using a microdrive for multitract microrecording. In addition to the Nexframe frameless system, we adopted the Leksell G frame to the same patients simultaneously to use a stereotactic X-ray system. This system consisted of a movable X-ray camera with a crossbar and was adopted to be always parallel to the frame with the X-ray film cassette. The distance between the expected and actual DBS electrode placements was measured on such a stereotactic X-ray system. In addition, the distance measured with this system was compared with that measured by conventional frame-based stereotaxy in 20 patients (40 sides). Results: The mean deviations from 10 planned targets were 1.3 ± 0.3 mm in the mediolateral (x) direction, 1.0 ± 0.9 mm in the anteroposterior (y) direction and 0.5 ± 0.6 mm in the superoposterior (z) direction. The data from the frame-based stereotaxy in our institute were 1.5 ± 0.9 mm in the mediolateral (x) direction, 1.1 ± 0.7 mm in the anteroposterior (y) direction and 0.8 ± 0.6 mm in the superoposterior (z) direction. Then, differences were not statistically significant in any direction (p > 0.05). The multitract microrecording procedure associated with the Nexframe was performed without any problems in all of the patients. None of these electrodes migrated during and/or after the surgery. However, the disadvantage of the system is the narrow surgical field for multiple electrode insertion. Coagulating the cortex and inserting multiple electrodes under such a narrow visual field were complicated. Conclusion: The Nexframe with multitract microrecording for STN DBS still has some problems that need to be resolved. Thus far, we do not consider that this technology in its present state can replace conventional frame-based stereotactic surgery. The accuracy of the system is similar to that of frame-based stereotaxy. However, the narrow surgical field is a disadvantage for multiple electrode insertion. Improvement on this point will enhance the usefulness of the system.
Microvascular Decompression of the Anterior Inferior Cerebellar Artery for Intermediate Nerve Neuralgia
Authors: Younes Walid M. , Capelle Hans-Holger , Krauss Joachim K.
Published: April 2010

The authors present the case of a 63-year-old woman with a 5-year history of intractable paroxysmal ‘atypical’ otofacial pain. The patient’s pain attacks were not typical for either trigeminal or vagoglossopharyngeal neuralgia. Surgical exploration via a suboccipital retromastoid craniotomy showed vascular compression of the nervus intermedius by the anterior inferior cerebellar artery and the patient’s pain was successfully managed with microvascular decompression.
Effects of Pregnancy, Hypertension and Nitric Oxide Inhibition on Rat Uterine Artery Myogenic Reactivity
Authors: Barron Carolyn , Mandala Maurizio , Osol George
Published: April 2010

Background/Aims: The purpose of this study was to examine the effects of hypertension and nitric oxide (NO) inhibition on myogenic tone in uterine arteries during pregnancy. Methods: Premyometrial radial uterine arteries from nonpregnant and late pregnant Sprague-Dawley rats were evaluated for myogenic reactivity from the following groups: control, hypertensive/NO-inhibited (L-NAME treatment) and normotensive/NO-inhibited (L-NAME plus hydralazine). Results: In both nonpregnant and pregnant animals, L-NAME treatment significantly elevated blood pressures, while the addition of hydralazine made the animals normotensive. In nonpregnant animals, little myogenic tone was seen in controls; tone increased significantly in the L-NAME group, and was attenuated in those treated with L-NAME plus hydralazine. In pregnant animals, controls developed significant tone; this was reduced in the L-NAME group, and returned to control levels in the L-NAME plus hydralazine group. Conclusions: Dimensional measurements showed that arteries from the pregnant hypertensive group did not undergo expansive remodeling, suggesting that tone development is related to phenotypic alterations in vascular smooth muscle and/or altered physical forces secondary to adaptive changes in arterial diameter. These differences implicate pregnancy-specific pathways in the development and inhibition of myogenic tone, and point to potentially opposing roles of NO and hypertension.
Upregulation of Proteinase-Activated Receptor-2 and Increased Response to Trypsin in Endothelial Cells after Exposure to Oxidative Stress in Rat Aortas
Authors: Aman Murasaki , Hirano Mayumi , Kanaide Hideo , Hirano Katsuya
Published: April 2010

Background/Aims: The effects of oxidative stress on the vascular responsiveness to the agonists of proteinase-activated receptors (PARs) were investigated. Methods: Serum-free incubation was utilized to impose oxidative stress to isolated rat aortas. Spontaneously hypertensive rats (SHR) were investigated as a model of in vivo oxidative stress. Results: Thrombin, trypsin, PAR1-activating peptide (PAR1-AP), PAR2-AP and PAR4-AP induced little or no effect in the aortas of female Wistar-Kyoto rats (WKY). Serum-free incubation induced endothelium-dependent relaxant responses to PAR2 agonists, but not PAR1 or PAR4 agonists, in a manner sensitive to diphenyleneiodonium or ascorbic acid. In male aortas, trypsin and PAR2-AP induced a transient endothelium-dependent relaxation without serum-free incubation. The acetylcholine-induced endothelium-dependent relaxation and the sodium nitroprusside-induced endothelium-independent relaxation remained unchanged. Immunoblot analyses revealed the upregulation of PAR2 in endothelial cells, which was abolished by either diphenyleneiodonium or ascorbic acid. Aortas of female SHR expressed a higher level of PAR2 than WKY and responded to trypsin without serum-free incubation. Treatment with ascorbic acid attenuated the trypsin-induced relaxation and the PAR2 expression in SHR. Conclusion: This study provides the first evidence that oxidative stress upregulates PAR2 in endothelial cells, thereby enhancing the endothelium-dependent relaxant response to PAR2 agonists in rat aortas.
Lung Vascular Targeting Using Antibody to Aminopeptidase P: CT-SPECT Imaging, Biodistribution and Pharmacokinetic Analysis
Authors: Chrastina A. , Valadon P. , Massey K.A. , Schnitzer J.E.
Published: April 2010

Background/Aims: Aminopeptidase P (APP) is specifically enriched in caveolae on the luminal surface of pulmonary vascular endothelium. APP antibodies bind lung endothelium in vivo and are rapidly and actively pumped across the endothelium into lung tissue. Here we characterize the immunotargeting properties and pharmacokinetics of the APP-specific recombinant antibody 833c. Methods: We used in situ binding, biodistribution analysis and in vivo imaging to assess the lung targeting of 833c. Results: More than 80% of 833c bound during the first pass through isolated perfused lungs. Dynamic SPECT acquisition showed that 833c rapidly and specifically targeted the lungs in vivo, reaching maximum levels within 2 min after intravenous injection. CT-SPECT imaging revealed specific targeting of 833c to the thoracic cavity and co-localization with a lung perfusion marker, Tc99m-labeled macroaggregated albumin. Biodistribution analysis confirmed lung-specific uptake of 833c which declined by first-order kinetics (t½ = 110 h) with significant levels of 833c still present 30 days after injection. Conclusion: These data show that APP expressed in endothelial caveolae appears to be readily accessible to circulating antibody rather specifically in lung. Targeting lung-specific caveolar APP provides an extraordinarily rapid and specific means to target pulmonary vasculature and potentially deliver therapeutic agents into the lung tissue.
Genetic Variation in Innate Immunity Pathways and Their Potential Contribution to the SIRS/CARS Debate: Evidence from Human Studies and Animal Models
Authors: Kumpf Oliver , Schumann Ralf R.
Published: April 2010

The lack of a causal and successful treatment for sepsis has led to a re-evaluation of the condition’s pathopysiology. The failure of anti-inflammatory strategies has implied compensatory immunosuppression to play a central part in fatal clinical cases. While searching for novel therapeutic strategies, the question arose whether pro-inflammation (systemic inflammatory response syndrome, SIRS) or anti-inflammation (compensatory anti-inflammatory response syndrome, CARS) are dominant in sepsis, and may be counteracted by therapeutic measures. Here we ask whether in a given organism – man or mouse – the lack of any functional protein involved in this cascade may help in understanding the events. In humans, genetic variations exist, and some of them have functional consequences altering the inflammatory response to pathogens. In mice, knockout animals were created, which may assist us in understanding the SIRS/CARS cascade. Here we summarize data on genetic variations in the TLR- and cytokine system and their influence on course of infectious diseases and sepsis. In addition, we summarize animal experiments and conclude that both cascades may be needed for containing infection. Imbalances in both the pro- and anti-inflammatory system may be harmful. Thus, interventional strategies have to be introduced carefully, and in the future genetic profiling may be needed in order to tailor therapies in the best way.
Endogenous Inflammatory Molecules Engage Toll-Like Receptors in Cardiovascular Disease
Authors: Ionita Mihaela G. , Arslan Fatih , de Kleijn Dominique P.V. , Pasterkamp Gerard
Published: April 2010

Innate immunity is important in the pathogenesis and progression of cardiovascular disease. Innate immune cells express various pattern-recognition receptors, among which also Toll-like receptors (TLRs). TLRs occur in atherosclerotic lesions where they are triggered by both exogenous (bacterial and viral pathogens) and endogenous (tissue damage-associated) molecules. Several endogenous TLR activators are described in relation to atherosclerotic disease or ischemia-induced cardiac injury. Experimental animal models have proved the role of TLR endogenous activators in disease initiation and further development. Nowadays, researchers aim to unravel the exact mechanisms involved in the endogenous ligand-dependent TLR signaling and to discover new potential activators, released during pathological conditions such as atherosclerosis and related ischemic manifestations. This review provides an overview of the currently known endogenous molecules which trigger innate immunity via TLRs in cardiovascular disease.
Chemokine Ligand 2 Genetic Variants, Serum Monocyte Chemoattractant Protein-1 Levels, and the Risk of Coronary Artery Disease
Authors: van Wijk Diederik F. , van Leuven Sander I. , Sandhu Manjinder S. , Tanck Michael W. , Hutten Barbara A. , Wareham Nicholas J. , Kastelein John J.P. , Stroes Erik S.G. , Khaw Kay-Tee , Boekholdt S. Matthijs
Published: April 2010

Objective—

In humans, evidence about the association between levels of monocyte chemoattractant protein-1 (MCP-1), its coding gene chemokine (C-C motif) ligand 2 (
CCL2
), and risk of coronary artery disease (CAD) is contradictory.

Methods and Results—

We performed a nested case-control study in the prospective EPIC-Norfolk cohort investigating the relationship between
CCL2
single-nucleotide polymorphisms (SNPs), MCP-1 concentrations, and the risk of future CAD. Cases (n=1138) were apparently healthy men and women aged 45 to 79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n=2237) were matched by age, sex, and enrollment time. Using linear regression analysis no association between
CCL2
SNPs and MCP-1 serum concentrations became apparent, nor did we find a significant association between MCP-1 serum levels and risk of future CAD. Finally, Cox regression analysis showed no significant association between
CCL2
SNPs and the future CAD risk. In addition, we did not find any robust associations between the
CCL2
haplotypes and MCP-1 serum concentration or future CAD risk.

Conclusion—

Our data do not support previous publications indicating that MCP-1 is involved in the pathogenesis of CAD.
Repressors NFI and NFY Participate in Organ-Specific Regulation of von Willebrand Factor Promoter Activity in Transgenic Mice
Authors: Nassiri Marjan , Liu Ju , Kulak Stephen , Uwiera Richard R.E. , Aird William C. , Ballermann Barbara J. , Jahroudi Nadia
Published: April 2010

Objective—

To determine the role of repressors in cell type and organ-specific activation of von Willebrand factor (VWF) promoter sequences −487 to 247 in vivo.

Methods and Results—

Activation patterns of wild-type and mutant VWF promoters (sequences −487 to 247) containing mutations in repressors nuclear factor-I (NFI)- and nuclear factor Y (NFY)-binding sites were analyzed in transgenic mice. Mutation of the NFI-binding site activated the promoter in heart and lung endothelial cells, whereas mutation of the NFY-binding site activated the promoter in kidney vasculature. Immunofluorescence analyses showed that NFIB was predominant in heart and lung endothelial cells, whereas NFIX was predominantly detected in kidney endothelial cell nuclei. By using chromatin immunoprecipitation, we demonstrated that the distal lung-specific enhancer (containing a YY1 site) of the
VWF
gene is brought in proximity to the NFI binding site.

Conclusion—

The NFI and NFY repressors contribute differentially to organ-specific regulation of the VWF promoter, and the organ-specific action of NFI may reflect its organ-specific isoform distribution. In addition, the lung-specific enhancer region of the endogenous
VWF
gene may inhibit NFI repressor function through chromatin looping, which can approximate the 2 regions.
Farnesoid X Receptor Activation Prevents the Development of Vascular Calcification in ApoE
−/−
Mice With Chronic Kidney Disease
Authors: Miyazaki-Anzai Shinobu , Levi Moshe , Kratzer Adelheid , Ting Tabitha C. , Lewis Linda B. , Miyazaki Makoto
Published: April 2010

Rationale
:

Vascular calcification is highly associated with cardiovascular morbidity and mortality, especially in patients with chronic kidney disease. The nuclear receptor farnesoid X receptor (FXR) has been implicated in the control of lipid, carbohydrate and bile acid metabolism in several cell types. Although recent studies have shown that FXR is also expressed in vascular smooth muscle cells, its physiological role in vasculature tissue remains obscure.

Objective
:

Here, we have examined the role of FXR in vascular calcification.

Methods and Results
:

The FXR gene, a bile acid nuclear receptor, was highly induced during osteogenic differentiation of bovine calcifying vascular cells (CVCs) and in the aorta of apolipoprotein (Apo)E
−/−
mice with chronic kidney disease which are common tissue culture and mouse model, respectively, for aortic calcification. FXR activation by a synthetic FXR agonist, 6α-ethyl chenodeoxycholic acid (INT-747) inhibited phosphate induced-mineralization and triglyceride accumulation in CVCs. FXR dominant negative expression augmented mineralization of CVCs and blocked the anticalcific effect of INT-747 whereas VP16FXR that is a constitutively active form reduced mineralization of CVCs. INT-747 treatment also increased phosphorylated c-Jun N-terminal kinase (JNK). SP600125 (specific JNK inhibitor) significantly induced mineralization of CVCs and alkaline phosphatase expression, suggesting that the anticalcific effect of INT-747 is attributable to JNK activation. We also found that INT-747 ameliorates chronic kidney disease induced-vascular calcification in 5/6 nephrectomized ApoE
−/−
mice without affecting the development of atherosclerosis.

Conclusions
:

These observations provide direct evidence that FXR is a key signaling component in regulation of vascular osteogenic differentiation and, thus representing a promising target for the treatment of vascular calcification.
Modeling Adaptive Autonomous Agents
Authors: Maes Pattie
Published: April 2010

One category of research in Artificial Life is concerned with modeling and building so-called adaptive autonomous agents, which are systems that inhabit a dynamic, unpredictable environment in which they try to satisfy a set of time-dependent goals or motivations. Agents are said to be adaptive if they improve their competence at dealing with these goals based on experience. Autonomous agents constitute a new approach to the study of Artificial Intelligence (AI), which is highly inspired by biology, in particular ethology, the study of animal behavior. Research in autonomous agents has brought about a new wave of excitement into the field of AI. This paper reflects on the state of the art of this new approach. It attempts to extract its main ideas, evaluates what contributions have been made so far, and identifies its current limitations and open problems.
Chaos as a Source of Complexity and Diversity in Evolution
Authors: Kaneko Kunihiko
Published: April 2010

The relevance of chaos to evolution is discussed in the context of the origin and maintenance of diversity and complexity. Evolution to the edge of chaos is demonstrated in an imitation game. As an origin of diversity, dynamic clustering of identical chaotic elements, globally coupled each to the other, is briefly reviewed. The clustering is extended to nonlinear dynamics on hypercubic lattices, which enables us to construct a self-organizing genetic algorithm. A mechanism of maintenance of diversity, “homeochaos,” is given in an ecological system with interaction among many species. Homeochaos provides a dynamic stability sustained by high-dimensional weak chaos. A novel mechanism of cell differentiation is presented, based on dynamic clustering. Here, a new concept—“open chaos”—is proposed for the instability in a dynamical system with growing degrees of freedom. It is suggested that studies based on interacting chaotic elements can replace both top-down and bottom-up approaches.