bluuebunny/crossref_metadata_2025 huggingface dataset:
Scrapie Resistance in ARQ Sheep
Authors: Laegreid W. W. , Clawson M. L. , Heaton M. P. , Green B. T. , O'Rourke K. I. , Knowles D. P.
Published: July 2008

Variation in the ovine prion protein amino acid sequence influences scrapie progression, with sheep homozygous for A136R154Q171considered susceptible. This study examined the association of survival time of scrapie-exposed ARQ sheep with variation elsewhere in the ovine prion gene. Four single nucleotide polymorphism alleles were associated with prolonged survival. One nonsynonymous allele (T112) was associated with an additional 687 days of survival for scrapie-exposed sheep compared to M112 sheep (odds ratio, 42.5;P= 0.00014). The only two sheep homozygous for T112 (TARQ) did not develop scrapie, suggesting that the allelic effect may be additive. These results provide evidence that TARQ sheep are genetically resistant to development of classical scrapie.
Differential Cholesterol Binding by Class II Fusion Proteins Determines Membrane Fusion Properties
Authors: Umashankar M. , Sánchez-San Martín Claudia , Liao Maofu , Reilly Brigid , Guo Alice , Taylor Gwen , Kielian Margaret
Published: July 2008

The class II fusion proteins of the alphaviruses and flaviviruses mediate virus infection by driving the fusion of the virus membrane with that of the cell. These fusion proteins are triggered by low pH, and their structures are strikingly similar in both the prefusion dimer and the postfusion homotrimer conformations. Here we have compared cholesterol interactions during membrane fusion by these two groups of viruses. Using cholesterol-depleted insect cells, we showed that fusion and infection by the alphaviruses Semliki Forest virus (SFV) and Sindbis virus were strongly promoted by cholesterol, with similar sterol dependence in laboratory and field isolates and in viruses passaged in tissue culture. The E1 fusion protein from SFV bound cholesterol, as detected by labeling with photocholesterol and by cholesterol extraction studies. In contrast, fusion and infection by numerous strains of the flavivirus dengue virus (DV) and by yellow fever virus 17D were cholesterol independent, and the DV fusion protein did not show significant cholesterol binding. SFV E1 is the first virus fusion protein demonstrated to directly bind cholesterol. Taken together, our results reveal important functional differences conferred by the cholesterol-binding properties of class II fusion proteins.
Identification of an Arginine-Rich Motif in Human Papillomavirus Type 1 E1^E4 Protein Necessary for E4-Mediated Inhibition of Cellular DNA Synthesis In Vitro and in Cells
Authors: Roberts Sally , Kingsbury Sarah R. , Stoeber Kai , Knight Gillian L. , Gallimore Phillip H. , Williams Gareth H.
Published: July 2008

Productive infections by human papillomaviruses (HPVs) are restricted to nondividing, differentiated keratinocytes. HPV early proteins E6 and E7 deregulate cell cycle progression and activate the host cell DNA replication machinery in these cells, changes essential for virus synthesis. Productive virus replication is accompanied by abundant expression of the HPV E4 protein. Expression of HPV1 E4 in cells is known to activate cell cycle checkpoints, inhibiting G
2
-to-M transition of the cell cycle and also suppressing entry of cells into S phase. We report here that the HPV1 E4 protein, in the presence of a soluble form of the replication-licensing factor (RLF) Cdc6, inhibits initiation of cellular DNA replication in a mammalian cell-free DNA replication system. Chromatin-binding studies show that E4 blocks replication initiation in vitro by preventing loading of the RLFs Mcm2 and Mcm7 onto chromatin. HPV1 E4-mediated replication inhibition in vitro and suppression of entry of HPV1 E4-expressing cells into S phase are both abrogated upon alanine replacement of arginine 45 in the full-length E4 protein (E1^E4), implying that these two HPV1 E4 functions are linked. We hypothesize that HPV1 E4 inhibits competing host cell DNA synthesis in replication-activated suprabasal keratinocytes by suppressing licensing of cellular replication origins, thus modifying the phenotype of the infected cell in favor of viral genome amplification.
SPIN ROTATION AND POLARIZATION OF TRANSPORT ELECTRONS THROUGH A THREE-ELECTRODE AHARONOV–BOHM RING WITH SPIN-ORBIT COUPLING
Authors: FEI HONG-MING , LI ZHI-JIAN , NIE YI-HANG , LIANG JIU-QING
Published: July 2008

The quantum transport of electrons through a three-lead ballistic Aharonov–Bohm (AB) ring with the Rashba spin-orbit interaction is revisited in terms of the S-matrix method from which the transmission probabilities are obtained analytically. It is shown that this mesoscopic device indeed can act as a spin-filter resulting in a relative spin-rotation between the input and output states while can act as a spin polarizer or splitter for a completely unpolarized, mixture input-state. In contrast with the result of Griffith's boundary conditions, the backscattering of carriers on the junction does not allow this three-terminal device to have unit efficiency. In addition, we point out that the AB ring with two symmetrically situated output leads also can give rise to the redistribution of the outgoing currents with respect to the variation of magnetic flux.
COMMON EIGENVECTORS OF N PARTICLES' COMPATIBLE OBSERVABLES AND ITS SQUEEZING OPERATOR
Authors: XU SHI-MIN , XU XING-LEI , LI HONG-QI
Published: July 2008

We construct 2N operators for a N-particle system, namely one center-of-mass coordinate operator, N-1 relative coordinate operators, one total momentum operator and N-1 mass-weighted relative momentum operators, and give common eigenvectors of N compatible observables [Formula: see text], which are composed of N particles' coordinate [Formula: see text] and momentum [Formula: see text]. By compatible, we mean such observables can be simultaneously determined. Using the technique of integration within an ordered product of operators (IWOP), we prove that the common eigenvectors are complete and orthonormal, and hereby qualified for making up a representation. This new representation can be applied to solving some dynamic problems in quantum mechanics.
A STUDY ON THE SECOND-ORDER NONLINEAR OPTICAL PROPERTIES OF AZO-DYE CHROMOPHORES CONTAINING THE ELECTRON-ACCEPTOR GROUP
Authors: WANG CHUANYU , HE TINGCHAO , WANG CHANGSHUN , HUI YANG , LU GUOYUAN
Published: July 2008

Two new azo-dye chromophores containing different electron-acceptor groups were synthesized and characterized by 1 H NMR, FT-IR and UV-vis spectra, respectively. The second-order nonlinearity of azo-dyes doped films in poly (methylmethacrylate) and the first hyperpolarizability of the azo molecules were investigated by the Maker Fringe method and the solvatochromic method, respectively. Experimental results showed that both of the two dyes exhibited large second-order nonlinearity (d33 > 30 pm/v) and the stronger electron-acceptor groups in dye molecules would induce larger second-order nonlinearity. This was confirmed by the measurement of the first hyperpolarizability.
COMPARISON OF STEADY-STATE AND TRANSIENT ELECTRON TRANSPORT IN InAs, InP AND GaAs
Authors: ARABSHAHI H. , KHALVATI M. R. , ROKN-ABADI M. REZAEE
Published: July 2008

An ensemble Monte Carlo simulation is used to compare high field electron transport in bulk InAs , InP and GaAs . In particular, velocity overshoot and electron transit times are examined. For all materials, we find that electron velocity overshoot only occurs when the electric field is increased to a value above a certain critical field, unique to each material. This critical field is strongly dependent on the material, about 400 kVm-1 for the case of GaAs , 300 kVm-1 for InAs and 700 kVm-1 for InP . We find that InAs exhibits the highest peak overshoot velocity and that this velocity overshoot lasts over the longest distances when compared with GaAs and InP . Finally, we estimate the minimum transit time across a 1 μm GaAs sample to be a bout 3 ps. Similar calculations for InAs and InP yield 2.2 and 5 ps, respectively. The steady-state and transient velocity overshoot characteristics are in fair agreement with other recent calculations.
SKELETON-BASED SHAPE CLASSIFICATION USING PATH SIMILARITY
Authors: BAI XIANG , YANG XINGWEI , YU DEGUANG , LATECKI LONGIN JAN
Published: July 2008

Most of the traditional methods for shape classification are based on contour. They often encounter difficulties when dealing with classes that have large nonlinear variability, especially when the variability is structural or due to articulation. It is well-known that shape representation based on skeletons is superior to contour based representation in such situations. However, approaches to shape similarity based on skeletons suffer from the instability of skeletons, and matching of skeleton graphs is still an open problem.

Using a new skeleton pruning method, we are able to obtain stable pruned skeletons even in the presence of significant contour distortions. We also propose a new method for matching of skeleton graphs. In contrast to most existing methods, it does not require converting of skeleton graphs to trees and it does not require any graph editing. Shape classification is done with Bayesian classifier. We present excellent classification results for complete shapes.
NONHYPERBOLIC BOUNDARY EQUILIBRIUM BIFURCATIONS IN PLANAR FILIPPOV SYSTEMS: A CASE STUDY APPROACH
Authors: DI BERNARDO MARIO , PAGANO DANIEL J. , PONCE ENRIQUE
Published: July 2008

Boundary equilibrium bifurcations in piecewise smooth discontinuous systems are characterized by the collision of an equilibrium point with the discontinuity surface. Generically, these bifurcations are of codimension one, but there are scenarios where the phenomenon can be of higher codimension. Here, the possible collision of a nonhyperbolic equilibrium with the boundary in a two-parameter framework and the nonlinear phenomena associated with such collision are considered.

By dealing with planar discontinuous (Filippov) systems, some of such phenomena are pointed out through specific representative cases. A methodology for obtaining the corresponding biparametric bifurcation sets is developed.
A CHAOTIC SYSTEM WITH ONE SADDLE AND TWO STABLE NODE-FOCI
Authors: YANG QIGUI , CHEN GUANRONG
Published: July 2008

This paper reports the finding of a chaotic system with one saddle and two stable node-foci in a simple three-dimensional (3D) autonomous system. The system connects the original Lorenz system and the original Chen system and represents a transition from one to the other. The algebraical form of the chaotic attractor is very similar to the Lorenz-type systems but they are different and, in fact, nonequivalent in topological structures. Of particular interest is the fact that the chaotic system has a chaotic attractor, one saddle and two stable node-foci. To further understand the complex dynamics of the system, some basic properties such as Lyapunov exponents, bifurcations, routes to chaos, periodic windows, possible chaotic and periodic-window parameter regions, and the compound structure of the system are analyzed and demonstrated with careful numerical simulations.
STRUCTURE-INDUCED BIFURCATION IN LARGE-SCALE ELECTRIC POWER SYSTEMS
Authors: LI SHAO-HUA , CHIANG HSIAO-DONG
Published: July 2008

A structure-induced bifurcation of nonsmooth nonlinear systems is studied and illustrated on electric power system models. The consequence of structure-induced bifurcation is an immediate instability induced by generator reactive power limits. It is numerically shown that structure-induced bifurcation can occur at both small power systems and large-scale power systems. Without taking the structure-induced bifurcation into account in defining power system operating limits, the resulting operating limits can be overly optimistic.
UNIFORM CONVERGENCE OF MONOTONE MEASURE DIFFERENTIAL INCLUSIONS: WITH APPLICATION TO THE CONTROL OF MECHANICAL SYSTEMS WITH UNILATERAL CONSTRAINTS
Authors: LEINE REMCO I. , VAN DE WOUW NATHAN
Published: July 2008

In this paper, we present theorems which give sufficient conditions for the uniform convergence of measure differential inclusions with certain maximal monotonicity properties. The framework of measure differential inclusions allows us to describe systems with state discontinuities. Moreover, we illustrate how these convergence results for measure differential inclusions can be exploited to solve tracking problems for certain classes of nonsmooth mechanical systems with friction and one-way clutches. Illustrative examples of convergent mechanical systems are discussed in detail.
OSCILLATION AND PERIOD DOUBLING IN TCP/RED SYSTEM: ANALYSIS AND VERIFICATION
Authors: CHEN XI , WONG SIU-CHUNG , TSE CHI K. , LAU FRANCIS C. M.
Published: July 2008

It has been known that a bottleneck RED (Random Early Detection) gateway can become oscillatory when regulating multiple identical TCP (Transmission Control Protocol) flows. However, a systematic explanation of such oscillatory behavior is not available. In this paper, we first use the fluid-flow model to derive the system characteristic frequency, and then compare with the frequencies of the RED queue length waveforms observed from "ns-2" simulations. The "ns-2" simulator is the only viable simulation tool accepted by industry for verification purposes. Analysis of the TCP source frequency distribution reveals the occurrence of period doubling when the system enters the instability region as the filter resolution varies. Since random events and a large number of TCP flows are involved in the process of generating the average system dynamics, a statistical viewpoint is taken in the analysis. Our results reflect the true system behavior as they are based on data from "ns-2" simulations rather than numerical simulations of analytical models. The physical mechanism of oscillation is explained in terms of the difference in the TCP source frequency and the TCP-RED system characteristic frequency.
Integrin VLA-4 enhances sialyl-Lewisx/a-negative melanoma adhesion to and extravasation through the endothelium under low flow conditions
Authors: Liang Shile , Dong Cheng
Published: July 2008

During their passage through the circulatory system, tumor cells undergo extensive interactions with various host cells including endothelial cells. The capacity of tumor cells to form metastasis is related to their ability to interact with and extravasate through endothelial cell layers, which involves multiple adhesive interactions between tumor cells and endothelium (EC). Thus it is essential to identify the adhesive receptors on the endothelial and melanoma surface that mediate those specific adhesive interactions. P-selectin and E-selectin have been reported as adhesion molecules that mediate the cell-cell interaction of endothelial cells and melanoma cells. However, not all melanoma cells express ligands for selectins. In this study, we elucidated the molecular constituents involved in the endothelial adhesion and extravasation of sialyl-Lewisx/a-negative melanoma cell lines under flow in the presence and absence of polymorphonuclear neutrophils (PMNs). Results show the interactions of α4β1 (VLA-4) on sialyl-Lewisx/a-negative melanoma cells and vascular adhesion molecule (VCAM-1) on inflamed EC supported melanoma adhesion to and subsequent extravasation through the EC in low shear flow. These findings provide clear evidence for a direct role of the VLA-4/VCAM-1 pathway in melanoma cell adhesion to and extravasation through the vascular endothelium in a shear flow. PMNs facilitated melanoma cell extravasation under both low and high shear conditions via the involvement of distinct molecular mechanisms. In the low shear regime, β2-integrins were sufficient to enhance melanoma cell extravasation, whereas in the high shear regime, selectin ligands and β2-integrins on PMNs were necessary for facilitating the melanoma extravasation process.
Hypotonicity and peptide discharge from a single vesicle
Authors: Jorgačevski Jernej , Stenovec Matjaž , Kreft Marko , Bajić Aleksandar , Rituper Boštjan , Vardjan Nina , Stojilkovic Stanko , Zorec Robert
Published: July 2008

Neuroendocrine secretory vesicles discharge their cargo in response to a stimulus, but the nature of this event is poorly understood. We studied the release of the pituitary hormone prolactin by hypotonicity, because this hormone also contributes to osmoregulation. In perfused rat lactotrophs, hypotonicity resulted in a transient increase followed by a sustained depression of prolactin release, as monitored by radioimmunoassay. In single cells imaged by confocal microscopy, hypotonicity elicited discharge of the fluorescently labeled atrial natriuretic peptide cargo from ∼2% of vesicles/cell. In contrast, KCl-induced depolarization resulted in a response of ∼10% of vesicles/cell, with different unloading/loading time course of the two fluorescent probes. In cell-attached studies, discrete changes in membrane capacitance were recorded in both unstimulated and stimulated conditions, reflecting single vesicle fusion/fissions with the plasma membrane. In stimulated cells, the probability of occurrence of full fusion events was low and unchanged, whereas over 95% of fusion events were transient, with the open fusion pore probability, the average pore dwell-time, the frequency of occurrence, and the fusion pore conductance increased. Hypotonicity only rarely elicited new fusion events in silent membrane patches. The results indicate that, in hypotonicity-stimulated lactotrophs, transient vesicle fusion mediates hormone release.
LPA modulates monocyte migration directly and via LPA-stimulated endothelial cells
Authors: Gustin Cindy , Van Steenbrugge Martine , Raes Martine
Published: July 2008

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid ligand present in oxidized low-density lipoprotein. The effects of LPA were investigated, first separately on endothelial cells (EC) and monocytes. Using Ki16425 (an LPA1 and LPA3 receptor antagonist), GW9662 [a peroxisome proliferator-activator receptor (PPARγ) antagonist], and pertussis toxin (that inhibits Gi/o), we demonstrate that LPA enhances IL-8 and monocyte chemoattractant protein-1 expression through a LPA1-, LPA3-, Gi/o- and PPARγ-dependent manner in the EAhy926 cells. The effect of LPA on chemokine overexpression was confirmed in human umbilical vein endothelial cells. LPA was able to enhance monocyte migration at concentrations <1 μM and to inhibit their migration at LPA concentrations >1 μM, as demonstrated by using a chemotaxis assay. We then investigated the effects of LPA on the cross-talk between EC and monocytes by evaluating the chemotactic activity in the supernatants of LPA-treated EC. At 1 μM LPA, both cell types respond cooperatively, favoring monocyte migration. At higher LPA concentration (25 μM), the chemotactic response varies as a function of time. After 4 h, the chemotactic effect of the cytokines secreted by the EC is counteracted by the direct inhibitory effect of LPA on monocytes. For longer periods of time (24 h), we observe a monocyte migration, probably due to lowered concentrations of bioactive LPA, given the induction of lipid phosphate phosphatase-2 in monocytes that may inactivate LPA. These results suggest that LPA activates EC to secrete chemokines that in combination with LPA itself might favor or not favor interactions between endothelium and circulating monocytes.
Responses of cardiac sympathetic nerve activity to changes in circulating volume differ in normal and heart failure sheep
Authors: Ramchandra Rohit , Hood Sally G. , Watson Anna M. D. , May Clive N.
Published: July 2008

Factors controlling cardiac sympathetic nerve activity (CSNA) in the normal state and those causing the large increase in activity in heart failure (HF) remain unclear. We hypothesized from previous clinical findings that activation of cardiac mechanoreceptors by the increased blood volume in HF may stimulate sympathetic nerve activity (SNA), particularly to the heart via cardiocardiac reflexes. To investigate the effect of volume expansion and depletion on CSNA we have made multiunit recordings of CSNA in conscious normal sheep and sheep paced into HF. In HF sheep ( n = 9) compared with normal sheep ( n = 9), resting levels of CSNA were significantly higher (34 ± 5 vs. 93 ± 2 bursts/100 heart beats, P < 0.05), mean arterial pressure was lower (76 ± 3 vs. 87 ± 2 mmHg; P < 0.05), and central venous pressure (CVP) was greater (3.0 ± 1.0 vs. 0.0 ± 1.0 mmHg; P < 0.05). In normal sheep ( n = 6), hemorrhage (400 ml over 30 min) was associated with a significant increase in CSNA (179 ± 16%) with a decrease in CVP (2.7 ± 0.7 mmHg). Volume expansion (400 ml Gelofusine over 30 min) significantly decreased CSNA (35 ± 12%) and increased CVP (4.7 ± 1.0 mmHg). In HF sheep ( n = 6) the responses of CSNA to both volume expansion and hemorrhage were severely blunted with no significant changes in CSNA or heart rate with either stimulus. In summary, these studies in a large conscious mammal demonstrate that in the normal state directly recorded CSNA increased with volume depletion and decreased with volume loading. In contrast, both of these responses were severely blunted in HF with no significant changes in CSNA during either hemorrhage or volume expansion.
High oxygen prevents fetal lethality due to lack of catecholamines
Authors: Ream Margie A. , Chandra Rashmi , Peavey Mary , Ray Alisa M. , Roffler-Tarlov Suzanne , Kim Hyung-Gun , Wetsel William C. , Rockman Howard A. , Chikaraishi Dona M.
Published: July 2008

The catecholamine norepinephrine is required for fetal survival, but its essential function is unknown. When catecholamine-deficient [tyrosine hydroxylase (Th) null] mouse fetuses die at embryonic day (E)13.5–14.5, they resemble wild-type (wt) fetuses exposed to hypoxia. They exhibit bradycardia (28% reduction in heart rate), thin ventricular myocardium (20% reduction in tissue), epicardial detachment, and death with vascular congestion, hemorrhage, and edema. At E12.5, before the appearance of morphological deficits, catecholamine-deficient fetuses are preferentially killed by experimentally induced hypoxia and have lower tissue Po2levels than wt siblings. By microarray analysis ( http://www.ncbi.nlm.nih.gov/geo ; accession no. GSE10341 ), hypoxia-inducible factor-1 target genes are induced to a greater extent in null fetuses than in wt siblings, supporting the notion that mutants experience lower oxygen tension or have an enhanced response to hypoxia. Hypoxia induces a 13-fold increase in plasma norepinephrine levels, which would be expected to increase heart rate, thereby improving oxygen delivery in wt mice. Surprisingly, increasing maternal oxygen (inspired O233 or 63%) prevents the effects of catecholamine deficiency, restoring heart rate, myocardial tissue, and survival of Th null fetuses to wt levels. We suggest that norepinephrine mediates fetal survival by maintaining oxygen homeostasis.
In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes
Authors: Edgley Amanda J. , Tare Marianne , Evans Roger G. , Skordilis Con , Parkington Helena C.
Published: July 2008

We assessed the relative contributions of endothelium-derived relaxing factors to renal vasodilation in vivo and determined whether these are altered in established streptozotocin-induced diabetes. In nondiabetic rats, stimulation of the endothelium by locally administered ACh or bradykinin-induced transient renal hyperemia. Neither basal renal blood flow (RBF) nor renal hyperemic responses to ACh or bradykinin were altered by blockade of prostanoid production (indomethacin) or by administration of charybdotoxin (ChTx) plus apamin to block endothelium-derived hyperpolarizing factor (EDHF). In contrast, combined blockade of nitric oxide (NO) synthase, Nω-nitro-l-arginine methyl ester (l-NAME), and prostanoid production reduced basal RBF and the duration of the hyperemic responses to ACh and bradykinin and revealed a delayed ischemic response to ACh. Accordingly, l-NAME and indomethacin markedly reduced integrated (area under the curve) hyperemic responses to ACh and bradykinin. Peak increases in RBF in response to ACh and bradykinin were not reduced by l-NAME and indomethacin but were reduced by subsequent blockade of EDHF. l-NAME plus indomethacin and ChTx plus apamin altered RBF responses to endothelium stimulation in a qualitatively similar fashion in diabetic and nondiabetic rats. The integrated renal hyperemic responses to ACh and bradykinin were blunted in diabetes, due to a diminished contribution of the component abolished by l-NAME plus indomethacin. We conclude that NO dominates integrated hyperemic responses to ACh and bradykinin in the rat kidney in vivo. After prior inhibition of NO synthase, EDHF mediates transient renal vasodilation in vivo. Renal endothelium-dependent vasodilation is diminished in diabetes due to impaired NO function.
Role of NF-κB and PI 3-kinase/Akt in TNF-α-induced cytotoxicity in microvascular endothelial cells
Authors: Zhou Zhu , Gengaro Patricia , Wang Wei , Wang Xue-qing , Li Chunling , Faubel Sarah , Rivard Christopher , Schrier Robert W.
Published: July 2008

The interaction of tumor necrosis factor (TNF)-α with the endothelium is a pivotal factor during endotoxemia. Inflammatory conditions are characterized by the activation of the transcription factor NF-κB and the expression of inflammatory mediators. Previous reports indicate that inhibition of NF-κB activation during sepsis may be beneficial to the microvasculature. In addition, the phosphatidylinositol-3-kinase/Akt signaling pathway (PI3-kinase/Akt) has been shown to be cytoprotective. In this study, we examined the effect of inhibition of NF-κB and PI3-kinase/Akt on cell viability, cytokine production, inducible nitric oxide synthase (iNOS) expression, and nitric oxide (NO) generation by TNF-α-treated cultured microvascular endothelial cells. TNF-α induced significant cytotoxicity and was associated with increased inflammatory cytokines and NO and increased expression of iNOS. The NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), prevented these increases and significantly attenuated the TNF-α-induced cytotoxicity. TNF-α also caused PI3-kinase/Akt activation, which was further increased by PDTC and prevented by the PI3-kinase inhibitor, LY294002. Inhibition of PI3-kinase/Akt also significantly potentiated TNF-α-mediated cytotoxicity. LY294002 treatment resulted in the appearance of increased apoptosis, compatible with the known anti-apoptotic properties of PI3-kinase/Akt. The present results therefore demonstrate a cytotoxic effect of TNF-α in microvascular endothelial cells which can be attenuated by NF-κB inhibition. In addition, PI3-kinase/Akt activation during TNF-α exposure may represent a compensatory anti-necrotic and anti-apoptotic pathway. The cytoprotective effects of NF-κB inhibition and PI3-kinase/Akt activation may have potential implications in the treatment of endotoxemia and septic shock.
TRPV1 mediates the uterine capsaicin-induced NMDA NR2B-dependent cross-organ reflex sensitization in anesthetized rats
Authors: Peng Hsien-Yu , Chang Hung-Ming , Lee Shin-Da , Huang Pei-Chen , Chen Gin-Den , Lai Cheng-Hung , Lai Cheng-Yuan , Chiu Chun-Hsien , Tung Kwong-Chung , Lin Tzer-Bin
Published: July 2008

Spinal cord-mediated cross-organ sensitization between the uterus and the lower urinary tract may underlie the high concurrence of obstetrical/gynecological inflammation and chronic pelvic pain syndrome characterized by urogenital pain. However, the neural pathway and the neurotransmitters involved are still unknown. We tested the hypothesis that the excitation of capsaicin-sensitive primary afferent fibers arising from the uterus through the stimulation of transient receptor potential vanilloid 1 (TRPV1) induces cross-organ sensitization on the pelvic-urethra reflex activity. Capsaicin (1–1,000 μM, 0.05 ml) was instilled into the uterus to induce cross-organ reflex sensitization. Activation of capsaicin-sensitive primary afferent fibers by capsaicin instillation into the uterine horn sensitized the pelvic-urethra reflex activity that was reversed by an intrauterine pretreatment with capsaizepine, a TRPV1-selective antagonist. Intrathecal injection of AP5, a glutamatergic N-methyl-d-aspartate (NMDA) antagonist, and Co-101244, an NMDA NR2B-selective antagonist, both abolished the cross-organ reflex sensitization caused by capsaicin instillation. These results demonstrated that TRPV1 plays a crucial role in contributing to the capsaicin-sensitive primary afferent fibers mediating the glutamatergic NMDA-dependent cross-organ sensitization between the uterus and the lower urinary tract when there is a tissue injury.
Blockade of renal medullary bradykinin B2receptors increases tubular sodium reabsorption in rats fed a normal-salt diet
Authors: Sivritas Sema-Hayriye , Ploth David W. , Fitzgibbon Wayne R.
Published: July 2008

The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B2(BKB2) receptors to acutely increase papillary blood flow (PBF) and therefore Na+excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB2receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 μg·kg−1·h−1, treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na+excretion (urinary Na+extraction rate) and fractional Na+excretion by 40 ± 5% and 40 ± 4%, respectively ( P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB2receptors to increase Na+excretion independent of changes in inner medullary blood flow.
Origins of the inhibiting effects of nasal CPAP on nonnutritive swallowing in newborn lambs
Authors: Samson Nathalie , Roy Bianca , Ouimet Alain , Moreau-Bussière François , Dorion Dominique , Mayer Sandeep , Praud Jean-Paul
Published: July 2008

The present study investigated the mechanism by which continuous positive airway pressure (CPAP) suppresses nonnutritive swallowing (NNS) during quiet sleep (QS) in newborn lambs. Eighteen full-term lambs were chronically instrumented and evenly distributed into three separate groups to determine the extent to which modulation of NNS may be attributed to stimulation of upper airway and/or bronchopulmonary mechanoreceptors. Six lambs were tracheotomized, six other lambs underwent a two-step bilateral intrathoracic vagotomy, and the remaining six lambs underwent chronic laryngotracheal separation (isolated upper airway group). Forty-eight hours after surgery, each nonsedated lamb underwent polysomnographic recordings on three consecutive days. States of alertness, NNS and respiratory movements were recorded. Results demonstrate that a CPAP of 6 cmH2O inhibited NNS during QS while administered directly on the lower airways and that bivagotomy prevented this inhibition. However, application of CPAP on the upper airways only also inhibited NNS during QS. Finally, the application of a CPAP of 6 cmH2O had no systematic effect on NNS-breathing coordination (assessed by the respiratory phase preceding and following NNS). In conclusion, our results suggest that bronchopulmonary receptors are implicated in the inhibiting effects of nasal CPAP of 6 cmH2O on NNS in all our experimental conditions, whereas upper airway receptors are only implicated in certain conditions.
Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury
Authors: Kan Wen-Hong , Hsu Jun-Te , Schwacha Martin G. , Choudhry Mashkoor A. , Raju Raghavan , Bland Kirby I. , Chaudry Irshad H.
Published: July 2008

Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35–40 mmHg for ∼90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or l-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma α-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1α, ICAM-1, IL-6, TNF-α, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of l-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.
Neuronal Responses to Moving Targets in Monkey Frontal Eye Fields
Authors: Cassanello Carlos R. , Nihalani Abhay T. , Ferrera Vincent P.
Published: July 2008

Due to delays in visuomotor processing, eye movements directed toward moving targets must integrate both target position and velocity to be accurate. It is unknown where and how target velocity information is incorporated into the planning of rapid (saccadic) eye movements. We recorded the activity of neurons in frontal eye fields (FEFs) while monkeys made saccades to stationary and moving targets. A substantial fraction of FEF neurons was found to encode not only the initial position of a moving target, but the metrics (amplitude and direction) of the saccade needed to intercept the target. Many neurons also encoded target velocity in a nearly linear manner. The quasi-linear dependence of firing rate on target velocity means that the neuronal response can be directly read out to compute the future position of a target moving with constant velocity. This is demonstrated using a quantitative model in which saccade amplitude is encoded in the population response of neurons tuned to retinal target position and modulated by target velocity.
Canal and Otolith Contributions to Compensatory Tilt Responses in Pigeons
Authors: McArthur Kimberly L. , Dickman J. David
Published: July 2008

Gaze-stabilizing eye and head responses compensate more effectively for low-frequency rotational motion when such motion stimulates the otolith organs, as during earth-horizontal axis rotations. However, the nature of the otolith signal responsible for this improvement in performance has not been previously determined. In this study, we used combinations of earth-horizontal axis rotational and translational motion to manipulate the magnitude of net linear acceleration experienced by pigeons, under both head-fixed and head-free conditions. We show that phase enhancement of eye and head responses to low-frequency rotational motion was causally related to the magnitude of dynamic net linear acceleration and not the gravitational acceleration component. We also show that canal-driven and otolith-driven eye responses were both spatially and temporally appropriate to combine linearly, and that a simple linear model combining canal- and otolith-driven components predicted eye responses to complex motion that were consistent with our experimental observations. However, the same model did not predict the observed head responses, which were spatially but not temporally appropriate to combine according to the same linear scheme. These results suggest that distinct vestibular processing substrates exist for eye and head responses in pigeons and that these are likely different from the vestibular processing substrates observed in primates.
Heterogeneous Neuronal Responses to Frequency-Modulated Tones in the Primary Auditory Cortex of Awake Cats
Authors: Qin Ling , Wang JingYu , Sato Yu
Published: July 2008

Previous studies in anesthetized animals reported that the primary auditory cortex (A1) showed homogenous phasic responses to FM tones, namely a transient response to a particular instantaneous frequency when FM sweeps traversed a neuron's tone-evoked receptive field (TRF). Here, in awake cats, we report that A1 cells exhibit heterogeneous FM responses, consisting of three patterns. The first is continuous firing when a slow FM sweep traverses the receptive field of a cell with a sustained tonal response. The duration and amplitude of FM response decrease with increasing sweep speed. The second pattern is transient firing corresponding to the cell's phasic tonal response. This response could be evoked only by a fast FM sweep through the cell's TRF, suggesting a preference for fast FM. The third pattern was associated with the off response to pure tones and was composed of several discrete response peaks during slow FM stimulus. These peaks were not predictable from the cell's tonal response but reliably reflected the time when FM swept across specific frequencies. Our A1 samples often exhibited a complex response pattern, combining two or three of the basic patterns above, resulting in a heterogeneous response population. The diversity of FM responses suggests that A1 use multiple mechanisms to fully represent the whole range of FM parameters, including frequency extent, sweep speed, and direction.
Functional Connectivity in the Pontomedullary Respiratory Network
Authors: Segers Lauren S. , Nuding Sarah C. , Dick Thomas E. , Shannon Roger , Baekey David M. , Solomon Irene C. , Morris Kendall F. , Lindsey Bruce G.
Published: July 2008

Current models propose that a neuronal network in the ventrolateral medulla generates the basic respiratory rhythm and that this ventrolateral respiratory column (VRC) is profoundly influenced by the neurons of the pontine respiratory group (PRG). However, functional connectivity among PRG and VRC neurons is poorly understood. This study addressed four model-based hypotheses: 1) the respiratory modulation of PRG neuron populations reflects paucisynaptic actions of multiple VRC populations; 2) functional connections among PRG neurons shape and coordinate their respiratory-modulated activities; 3) the PRG acts on multiple VRC populations, contributing to phase-switching; and 4) neurons with no respiratory modulation located in close proximity to the VRC and PRG have widely distributed actions on respiratory-modulated cells. Two arrays of microelectrodes with individual depth adjustment were used to record sets of spike trains from a total of 145 PRG and 282 VRC neurons in 10 decerebrate, vagotomized, neuromuscularly blocked, ventilated cats. Data were evaluated for respiratory modulation with respect to efferent phrenic motoneuron activity and short-timescale correlations indicative of paucisynaptic functional connectivity using cross-correlation analysis and the “gravity” method. Correlogram features were found for 109 (3%) of the 3,218 pairs composed of a PRG and a VRC neuron, 126 (12%) of the 1,043 PRG–PRG pairs, and 319 (7%) of the 4,340 VRC–VRC neuron pairs evaluated. Correlation linkage maps generated for the data support our four motivating hypotheses and suggest network mechanisms for proposed modulatory functions of the PRG.
Effects of Simulated Increases in Body Weight from Birth on the Growth of Limb Bones in Rats
Authors: Simon Mark R. , Holmes Kenneth R. , Olsen Aar M.
Published: July 2008

The purpose of this study was to subject groups of newborn male and female Sprague-Dawley rats each to a specific 10% simulated increase in body weight, to a maximum of a doubling of body weight, to study the effects of quantified, increased, intermittent, compressive forces on limb bone growth. Chronic centrifugation was employed. After 90 days of centrifugation the rats were sacrificed. The humerus, radius, ulna, femur, and tibia were removed from each animal, cleared of all soft tissues, measured and weighed. Tukey’s Studentized multiple range test was performed to identify aggregations (sets) of force groups between which there are significant differences. The data suggest that newborn male and female rats subjected to simulated increases in body weight, within the range used for this study, undergo enhanced general body growth and limb bone growth.
Licht- und elektronenmikroskopische Untersuchungen zur Entwicklung der Prominentia spiralis im Ductus cochlearis von Meerschweinchenfeten
Authors: Thorn L. , Schinko I. , Wetzstein R.
Published: July 2008

The anlage of the spiral prominence can be seen on the 37th day of development as a small protrusion of the epithelium towards the lumen of the cochlear duct. During the further progress, the spiral prominence more distinctly protrudes by augmentation of the vascularized connective tissue. In the epithelial cells pinocytotic vesicles near the plasmalemma are seen earliest lateral and basal on the 37th day, apical on the 39th day. The epithelial cells send basal cytoplasmic extensions towards the connective tissue. Starting on the 44th day, small invaginations of connective tissue extend into the epithelium, remaining separated from the epithelial cells by the basal lamina. Until the 48th day, the monostratified epithelium remains columnar, thereafter it changes to cuboidal or flat. Towards the end of the development, the invaginations of the connective tissue nearly reach the surface of the epithelium, being separated from the endolymph by a small epithelial area.
Morphological and Histochemical Study of the Submandibular Gland in Praomys (Mastomys) natalensis
Authors: Sirigu Paola , DiDio Liberato J.A. , Gross Susan A. , Perra Maria T.
Published: July 2008

The submandibular gland in female and male Praomys (Mastomys) natalensis (a South African mul-timammate rodent) was studied using light microscopy and techniques for the demonstration of carbohydrates. Hematoxylin and eosin stain revealed the presence of a single secreting component that gave a strongly positive PAS reaction. Limiting elements of the granular tubules gave a weakly positive PAS reaction. Acidic glycoproteins were evidenced only in granules of the acinar component.
Possible Role of Endothelium in the Orientation of Smooth Muscle Cells in Experimental Neointima
Authors: Reimers D. , Gutierrez Diaz J.A. , Cuevas P. , Dujovny M. , Diaz F.G. , Ausman J.I.
Published: July 2008

Myointimal cells (MIC) orientation and intimal thickening evolution, induced by grafting an autogenous venous patch onto the rat common carotid artery, were studied with light microscopy at different times until 14 months after surgery. Intimal thickenings in the venous patch were most prominent at an intermediate postoperative period, after which their mean size did not change significantly. In host artery neointima, the greatest MIC proliferation was observed at a late stage of evolution. MIC arrangement was predominantly circumferential to the blood stream in venous patch neointima, whereas it was mostly axial in the host artery. The interaction between MIC orientation and endothelial regeneration in the operated vessel is discussed.
Anatomical Observations in the Pharynx of the Mouse with Special Reference to the Nasopharyngeal Hiatus (Wood Jones)
Authors: Nakano T. , Muto H.
Published: July 2008

The mouse pharynx, especially the muscles, was anatomically studied in detail considering the structures of the laryngeal cartilages and the hyoid bone. The nasopharyngeal sphincter was formed by the palatopharyngeus and the levator palati muscles. It was suggested that the former contracted the ‘palatopharyngeal eminence’ (named by the present authors) and the latter drew up the soft palate, then the nasopharyngeal hiatus was closed. At the rostral end of the esophagus, there existed the ‘thyro-pharyngo-esophageus muscle’, denominated by the present authors. It was suggested to represent in the area of the esophagopharynx and to compress the tube by any sphincteric functions.
Target Cells of Vitamin D in the Vertebrate Retina
Authors: Schreiner D.S. , Jande S.S. , Lawson D.E.M.
Published: July 2008

Using PAP technique, cellular localization of vitamin D-dependent calcium-binding protein (D-CaBP) was investigated in vertebrate retina with monospecific antisera against chick duodenal D-CaBP. In the chick retina, the receptor cells were positive. In the inner nuclear layer, horizontal cells and some bipolar cells were also positive. Some amacrine cells as well as different levels of the inner plexiform layer were also positive for D-CaBP. A few interspersed ganglion cells were positive but their axons forming the optic tract were negative. Müller’s cells were negative. In 1-day-old chicks and 4-week-old rachitic chicks there was paucity and absence, respectively, of D-CaBP staining in horizontal cells. In the mouse, rat, and rabbit the receptors had only trace amounts of reaction product in their outer segment and pedicle. Horizontal cells were densely positive throughout their cellular body and processes. Some amacrine cells in the inner nuclear layer were positive. In the mouse and rat three horizontal levels of the outer plexiform layer were very prominent because of their dense staining for D-CaBP. Many ganglion cells were also positive along with their axons forming the optic nerve. In the rabbit, no positive layers were seen in the inner plexiform layer, and ganglion cells with their fibers were negative. In the frog retina there were smaller amounts of D-CaBP in the receptor cells and horizontal cells than that of the chick retina. Also, the fibers of the ganglionic cells were positive for D-CaBP. In all species studied, some amacrine cells were stained for D-CaBP. Because of its possible roles in membrane calcium transport and intracellular Ca++ regulation, it has perhaps similar functions in these positive cells. The synthesis of D-CaBP is dependent upon vitamin D. These positive cells are thus target cells of vitamin D.
Demonstration of Hydroxysteroid Dehydrogenases and Testosterone in the Sertoli-Leydig Cell Tumor (Androblastoma) Tissue of the Human Ovary: An Enzyme Histochemical and Immunohistochemical Study
Authors: Haider Syed G. , Pickartz Heinz , Freundl Günter , Passia Dieter
Published: July 2008

Gynecological, endocrinological and histological tests on a 19-year-old female patient led to the diagnosis of Sertoli-Leydig cell tumor (arrhenoblastoma) of intermediate differentiation. For enzyme histochemical purposes the tumor tissue, removed from the right ovary by laparatomy, was frozen in liquid nitrogen. The following enzymes were demonstrated: nonspecific esterases, 3β-hydroxysteroid dehydrogenase (HSDH), 17β-HSDH, 11β-HSDH, and NADH tetrazolium reductase. Cryostat sections, prefixed with formaldehyde vapors, were used to localize testosterone production immunohistochemically with the PAP method. A large number of pseudotubules with Sertoli cells were observed; the Leydig cells in the interstitial space were often arranged in the form of islands. Strong nonspecific esterase activity weak 3β-HSDH activity, moderate 17β-HSDH activity, and strong 11β-HSDH activity were observed largely in the Leydig cells. Testosterone synthesis, demonstrated immunohistochemically, took place predominantly in the Leydig cells, but also to a small extent in the Sertoli cells.