bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of superoxide anion and elastase release in human neutrophils by 3′‐isopropoxychalconeviaa cAMP‐dependent pathway
Authors: Hwang Tsong‐Long , Yeh Shang‐Hsin , Leu Yann‐Lii , Chern Ching‐Yuh , Hsu Hui‐Chi
Published: February 2006

Chalcone is abundantly present in the plant kingdom and has various biological activities such as anti‐inflammatory and antioxidant. In this study, the semisynthetic chalcone derivative, 3′‐isopropoxychalcone (H2O7D), was demonstrated to inhibit the generation of superoxide and the release of elastase, as well as to accelerate resequestration of cytosolic calcium in formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine‐activated human neutrophils.

H2O7D displayed no antioxidant or superoxide‐scavenging ability, and it failed to alter the subcellular NADPH oxidase activity.

H2O7D induced a substantial increase in cAMP but not cGMP levels. The elevation of cAMP formation by H2O7D was inhibited by adenosine deaminase (ADA). Furthermore, The inhibitory effects of H2O7D were reversed by protein kinase (PK)A inhibitors, as well as ADA and a selective A2a‐receptor antagonist.

H2O7D inhibited phosphodiesterase (PDE) activities, but it did not alter adenylyl cyclase and soluble guanylyl cyclase activities. These results show that the cAMP‐elevating effect of H2O7D results from the inhibition of PDE activity and not from the stimulation of cyclase function. Consistent with this, H2O7D potentiated the PGE1‐caused inhibitory effects and cAMP formation.

In summary, these results indicate that the inhibitory effect of H2O7D is cAMP/PKA dependent, and that it occurs through inhibition of cAMP PDE, which potentiates the autocrine functions of endogenous adenosine. Inhibition of respiratory burst and degranulation in human neutrophils may give this drug the potential to protect against the progression of inflammation.

British Journal of Pharmacology(2006)148, 78–87. doi:10.1038/sj.bjp.0706712
Irreversible adsorption of tethered chains at substrates: Monte Carlo study
Authors: Descas Radu , Sommer Jens-Uwe , Blumen Alexander
Published: February 2006

The irreversible adsorption of single chains grafted with one end to the surface is studied using scaling arguments and computer simulations. We introduce a two-phase model, in which the chain is described by an adsorbate portion and a corona portion formed by nonadsorbed monomers. The adsorption process can be viewed as consisting of a main stage, during which monomers join by “zipping” (along their order in the chain) the surface, and a late stage, in which the remaining corona collapses on the surface. Based on our model we derive a scaling relation for the time of adsorption t(M) as a function of the number M of adsorbed monomers; t(M) follows a power law, Mα, with α>1. We find that α is related to the Flory exponent ν by α=1+ν. Using further scaling arguments we derive relations between the overall time of adsorption, the characteristic time of adsorption (given by the crossover time between the main and the last stage of adsorption), and the chain length. To support our analysis we perform Monte Carlo simulations using the bond fluctuation model. In particular, the sequence of adsorption events is very well reproduced by the simulations, and an analysis of the various density profiles supports our theoretical model. Especially the loop formation during adsorption clearly shows that the growth of the adsorbate is dominated by zipping. The simulations are also in almost quantitative agreement with our theoretical scaling analysis, showing that here the assumption of a linear relation between Monte Carlo steps and time is well obeyed. We conclude by also discussing the geometrical shape of the adsorbate.
Multiple time step update schemes for dissipative particle dynamics
Authors: Jakobsen Ask F. , Besold Gerhard , Mouritsen Ole G.
Published: February 2006

In dynamical simulations of coarse-grained models of soft matter in a solvent a considerable amount of the total simulation time is generically spent on updating the solvent particles, although their dynamics is in most cases not of primary interest. In order to speed up such simulations and as a consequence allow to extend them to cover larger system sizes, we propose and examine various multiple, specifically dual, time step update algorithms for dissipative particle dynamics simulations that are based on the velocity-Verlet scheme [Phys. Rev. 159, 98 (1967)]. Common to all update variants is that the solvent beads are updated with a lower frequency than the bonded interactions within the solute. As a test case we consider a coarse-grained model of a lipid bilayer in water. Our results demonstrate that a considerable saving of simulation time can be gained, while the obtained simulation data are within error brackets virtually identical to those obtained for the reference single time step update scheme.
Interaction of D2 with H2O amorphous ice studied by temperature-programed desorption experiments
Authors: Amiaud L. , Fillion J. H. , Baouche S. , Dulieu F. , Momeni A. , Lemaire J. L.
Published: February 2006

The gas-surface interaction of molecular hydrogen D2 with a thin film of porous amorphous solid water (ASW) grown at 10K by slow vapor deposition has been studied by temperature-programed-desorption (TPD) experiments. Molecular hydrogen diffuses rapidly into the porous network of the ice. The D2 desorption occurring between 10 and 30K is considered here as a good probe of the effective surface of ASW interacting with the gas. The desorption kinetics have been systematically measured at various coverages. A careful analysis based on the Arrhenius plot method has provided the D2 binding energies as a function of the coverage. Asymmetric and broad distributions of binding energies were found, with a maximum population peaking at low energy. We propose a model for the desorption kinetics that assumes a complete thermal equilibrium of the molecules with the ice film. The sample is characterized by a distribution of adsorption sites that are filled according to a Fermi-Dirac statistic law. The TPD curves can be simulated and fitted to provide the parameters describing the distribution of the molecules as a function of their binding energy. This approach contributes to a correct description of the interaction of molecular hydrogen with the surface of possibly porous grain mantles in the interstellar medium.
Application of a two-length-scale field theory to the solvation of neutral and charged molecules
Authors: Sitnikov G. , Taran M. , Muryshev A. , Nechaev S.
Published: February 2006

We develop a continuous self-consistent theory of solute-water interactions that allows determination of the hydrophobic layer around a solute molecule of any geometry, with an explicit account of solvent structure described by its correlation function. We compute the mean solvent density profile n(r) surrounding the solute molecule as well as its solvation free energy ΔG. We compare the two-length-scale field theory to the numerical data of Monte Carlo simulations found in the literature for spherical molecules and discuss the possibility of self-consistent adjustment of the free parameters of the theory. In the framework of this approach, we compute the solvation free energies of alkane molecules and the free energy of interaction of two spheres of radius R separated by the distance D. We describe the general setting of the self-consistent account of electrostatic interactions in the framework of our model where the water is considered not as a continuous medium but as a gas of dipoles. We analyze the limiting cases where the proposed theory coincides with the electrostatics of a continuous medium.
Methodology for determining the influence of soft surface layers in porous solids on compressive behavior: Application to NASA’s lightweight ceramic ablator
Authors: Gray Mike H. B. , Milstein Frederick
Published: February 2006

A methodology is presented for determining the compressive response of a porous material’s surface layer. Microscopic strain measurements are combined with an analytical model that describes the strain in the surface layer, at a given compressive stress, as a nonlinear function of surface depth. The model yields the effective thickness of the surface layer, explains quantitatively an increase in apparent material stiffness with increasing sample thickness, and yields accurate stress-strain curves (prior to yielding) for samples of arbitrary thickness. The methodology is applied successfully to silicone impregnated reusable ceramic ablator, a thermal protection system material developed and used by NASA for planetary missions, including the Mars rovers.
Ultrafast x-ray imaging with sliced sampling streak cameras
Authors: Huang T. X. , Nakai M. , Shiraga H. , Azechi H. , Huang T. X. , Ding Y. K. , Zheng Z. J.
Published: February 2006

The ultrafast imaging methods in sliced sampling streak cameras are investigated. It is shown that the sampling-image x-ray streak camera has potential advantages in highly time-resolved and space-resolved imaging for imploded core plasmas. An optimized sampling method is presented to acquire two-dimensional spatial resolutions ⩽10μm and temporal resolution ∼10ps, within a field of view ∼100μm and a time range ∼100ps.
Plasma-reactive SiC quantum dots on polycrystalline AlN films
Authors: Huang S. Y. , Xu S. , Long J. D. , Sun Z. , Chen T.
Published: February 2006

The self-assembly of SiC quantum dots (SiC QDs) formed on AlN films is investigated. Under optimized growth conditions, SiC QDs with a remarkably narrow size distribution on polycrystalline AlN films can be achieved with the presence of a wetting layer of SiC film by low-frequency inductively coupled plasma- (LF-ICP-) assisted magnetron sputtering. A transmission electron microscope (TEM), field-emission scanning electron microscope (FE-SEM) images, and an energy-dispersive x-ray (EDX) spectrometer clearly demonstrate that SiC QDs are formed on the polycrystalline AlN films.
A theoretical investigation of hyperpolarizability for small GanAsm (n+m=4–10) clusters
Authors: Lan Y.-Z. , Cheng W.-D. , Wu D.-S. , Shen J. , Huang S.-P. , Zhang H. , Gong Y.-J. , Li F.-F.
Published: February 2006

In this paper, the second and third order polarizabilities of small GanAsm (n+m=4–10) clusters are systematically investigated using the time dependent density functional theory (TDDFT)∕6-311+G* combined with the sum-over-states method (SOS∕∕TDDFT∕6-311+G*). For the static second order polarizabilities, the two-level term (βvec.2) makes a significant contribution to the βvec for all considered GanAsm clusters except for the Ga3As4 cluster. And, for the static third order polarizabilities, the positive channel (⟨γ⟩II) makes a larger contribution to ⟨γ⟩tot than the negative channel (⟨γ⟩I). Similar to the cubic GaAs bulk materials, the small GanAsm cluster assembled materials exhibit large second order (1×10−6esu) and third order susceptibilities (5×10−11esu). The dynamic behavior of β(−2ω;ω,ω) and γ(−3ω;ω,ω,ω) show that the small GanAsm cluster will be a good candidate of nonlinear optical materials due to the avoidance of linear resonance photoabsorption.
On the influence of microsolvation by argon atoms on the electron affinity properties of water dimer
Authors: Wielgus Pawel , Gora Robert W. , Szefczyk Borys , Roszak Szczepan , Leszczynski Jerzy
Published: February 2006

This work provides a comparison of neutral (H2O)2Arn and negatively charged (H2O)2−Arn complexes. The excess electron stabilizes the complexes and leads to the trans to cis rearrangement within the water dimer core. In the case of small complexes (n⩽4) the microsolvation of the dimer by argon atoms arises on the trans side with respect to the donor water molecule. The stabilization of an excess electron is enhanced by the delocalization of the electronic charge density due to microsolvation. The process of cis to trans rotation is induced by the electric field of the approaching negative charge. The interaction energy decomposition suggests a more ionic character of binding in the negatively charged complexes. The attachment of an electron is controlled by the correlation energy.
Calculations of partial cross sections for photofragmentation processes using complex absorbing potentials
Authors: Grozdanov T. P. , Andric L. , McCarroll R.
Published: February 2006

We investigate the use of complex absorbing potentials for the calculation of partial cross sections in multichannel photofragmentation processes. An exactly solvable, coupled-two-channel problem involving square-well potentials is used to compare the performance of various types of absorbing potentials. Special emphasis is given to the near-threshold regions and the conditions under which the numerical results are able to reproduce the Wigner threshold laws. It was found that singular, transmission-free absorbing potentials perform better than those of power or polynomial form.
Theoretical evidence for nonadiabatic vibrational deexcitation in H2(D2) state-to-state scattering from Cu(100)
Authors: Luntz A. C. , Persson M. , Sitz Greg O.
Published: February 2006

Dynamical calculations are presented for electronically nonadiabatic vibrational deexcitation of H2 and D2 in scattering from Cu(111). Both the potential energy surface and the nonadiabatic coupling strength were obtained from density functional calculations. The theoretically predicted magnitude of the deexcitation and its dependence on incident energy and isotope are all in agreement with state-to-state scattering experiments [on Cu(100)], and this gives indirect evidence for a nonadiabatic mechanism of the observed deexcitation. Direct evidence could be obtained by measuring the chemicurrent associated with the deexcitation, and its properties have been predicted.
Three-dimensional crystallization inside photosensitive glasses by focused femtosecond laser
Authors: Fisette B. , Busque F. , Degorce J.-Y. , Meunier M.
Published: February 2006

Using scanning electron microscopy, we analyze the laser fluence dependence of three-dimensional crystallized areas induced in bulk photosensitive glass (Foturan) by focused femtosecond laser pulses exposition and subsequent heat treatment. For low fluences (F<2J∕cm2), the crystallized area is essentially determined by the energy dose distribution above a critical dose. For higher fluences (F>2J∕cm2), the crystallization length is higher than predicted from the energy distribution due to the filamentation which occurs above a critical fluence Fcrit=1.4±0.3J∕cm2. The filamentation length is found to follow the square root dependence F−Fcrit.
On the non-Arrhenius behavior of negative-bias temperature instability
Authors: Ang D. S. , Wang S.
Published: February 2006

Evidence from negative-bias temperature stressing of the ultrathin Si3N4∕SiOx gate p-channel field-effect transistor indicates that non-Arrhenius behavior is a consequence of the superposition of two distinct defect generation mechanisms with different power-law time dependence (tn) and activation energy (Ea). The two mechanisms are (1) a hole trapping mechanism (t0.1; Ea∼0.02eV) and (2) the classical hydrogen diffusion mechanism (t0.25; Ea∼0.2–0.3eV). When temperature increases, the latter gradually dominates, causing the exponent n, of the overall time-dependent shift of the device threshold voltage (∣ΔVth∣1+2∝tn), to increase. Eliminating the contribution of the hole trapping mechanism, i.e. ∣ΔVth∣1 from overall threshold voltage shift consistently reproduces ∣ΔVth∣2∝tn characteristics which bear the classical signature of negative-bias temperature instability, i.e., n≈0.25 and is independent of temperature.
Properties of wurtzite w-MnN and of w-MnN inclusions in (Ga,Mn)N
Authors: Bogusławski P. , Bernholc J.
Published: February 2006

Mn ions in (Ga,Mn)N exhibit a tendency to form pairs, which is enhanced by ferromagnetic Mn–Mn coupling. We also find that segregation of Mn to form MnN clusters in the wurtzite structure of host GaN is energetically favorable. However, our first-principles calculations show that both w-MnN inclusions stretched to fit the lattice constant of GaN, and relaxed ones with the equilibrium lattice constant of MnN are antiferromagnetic, and thus they are not responsible for the high temperature ferromagnetism reported for (Ga,Mn)N. Incorporation of Mn on the N sites is prohibited by the high formation energy of MnN.
Adhesion and reinforcement in carbon nanotube polymer composite
Authors: Wei Chenyu
Published: February 2006

Temperature dependent adhesion behavior and reinforcement in carbon nanotube (CNT)-polymer (polyethylene) composite is studied through molecular dynamics simulations. The interfacial shear stress through van der Waals interactions is found to increase linearly with applied tensile strains along the nanotube axis direction, until the noncovalent bonds between CNTs and molecules break successively. A lower bound value about 46MPa is found for the shear strength at low temperatures. Direct stress-strain calculations show significant reinforcements in the composite in a wide temperature range, with ∼200% increase in the Young’s modulus when adding 6.5% volume ratio of short CNTs, and comparisons with the Halpin–Tsai formula are discussed.
Physical model of CdS-based thin-film photovoltaic junctions
Authors: Cooray M. L. C. , Karpov V. G.
Published: February 2006

We propose a simple physical model of CdS-based thin-film photovoltaic junctions including the major types that utilize the CdTe and Cu(In,Ga)Se2 absorber layers. This model allows for field reversal in the CdS layer. It is solved analytically, verified numerically, and predicts a variety of phenomena, such as the lack of carrier collection from CdS, buffer layer effects, light to dark current-voltage curve crossing and rollover.
Testing the Coplanar Ratio Hypothesis of Lightness Perception
Authors: Howe Piers D L
Published: February 2006

What determines an object's lightness remains unclear, but it is generally thought that the ratios of its luminance to the luminance of other objects in a scene play a crucial role because these ratios allow the relative reflectance of each object to be estimated, providing all the objects are under the same illumination. Because objects that lie in the same plane are typically illuminated equally, it has been suggested that it is the luminance ratios between coplanar objects that primarily determine lightness (Gilchrist, 1977 Science195 185–187; Gilchrist et al, 1999 Psychological Review106 795–834). An alternative hypothesis is that perceived illumination differences can affect lightness directly. As the studies that provided evidence for the coplanar ratio hypothesis always varied the illumination and the coplanar relationships simultaneously, it is unclear which hypothesis is correct. I measured the influence of each factor separately and found that the perceived illumination differences have a greater effect on lightness.
Perceiving Causality after the Fact: Postdiction in the Temporal Dynamics of Causal Perception
Authors: Choi Hoon , Scholl Brian J
Published: February 2006

In simple dynamic events we can easily perceive not only motion, but also higher-level properties such as causality, as when we see one object collide with another. Several researchers have suggested that such causal perception is an automatic and stimulus-driven process, sensitive only to particular sorts of visual information, and a major research project has been to uncover the nature of these visual cues. Here, rather than investigating what information affects causal perception, we instead explore the temporal dynamics of when certain types of information are used. Surprisingly, we find that certain visual events can determine whether we perceive a collision in an ambiguous situation even when those events occur after the moment of potential ‘impact’ in the putative collision has already passed. This illustrates a type of postdictive perception: our conscious perception of the world is not an instantaneous moment-by-moment construction, but rather is formed by integrating information presented within short temporal windows, so that new information which is obtained can influence the immediate past in our conscious awareness. Such effects have been previously demonstrated for low-level motion phenomena, but the present results demonstrate that postdictive processes can influence higher-level event perception. These findings help to characterize not only the ‘rules’ of causal perception, but also the temporal dynamics of how and when those rules operate.
Morphological variation and phylogenetic relationships within Eucalyptus series Subulatae (Myrtaceae) of southern Australia
Authors: Nicolle D. , Whalen M. A. , Mackay D. A.
Published: February 2006

Morphological variation within Eucalyptus series Subulatae, a group of mallee and woodland tree taxa distributed across southern Australia, was assessed by adult and seedling characteristics. A phenetic study included a total of 51 adult morphological characters and 37 seedling characters, which were assessed for 564 individuals representing 163 populations, covering the broad geographical distribution of the series. All taxa included in the series by either Johnson and Hill (1999) or Brooker (2000) were included together with E. angustissima, E. cooperiana, E. falcata and E. salmonophloia, all of which have been at times included in, or considered closely related to, E. ser. Subulatae. The phenetic analyses indicate that the four subseries of Brooker (2000) are morphologically distinct, although their distinctiveness is only evident from seedling characters. The two subseries that Johnson and Hill (1999) recognise (subser. Flocktonianosae and Transcontinentalosae) corresponding to Brooker’s (2000) subser. Decurrentes, are more weakly defined. Southern populations of E. dolichocera are not considered here to belong to this species but rather to belong to a different subseries based on seedling morphology. A phylogenetic analysis of 44 morphological characters and 23 species of E. ser. Subulatae and 24 species from variously related taxa suggest that E. ser. Subulatae may not be monophyletic. Eucalyptus brockwayi and E. salmonophloia are basal to E. ser. Subulatae and all of the other taxa included in the analysis. Within E. ser. Subulatae, subsers Oleaginae and Spirales are both monophyletic. Both the phylogenetic and phenetic analyses strongly suggest that E. brockwayi is unique in several characters, including some not previously recognised, and is best placed in a monotypic series. The position of E. aspersa remains unresolved, but is probably best retained in E. subser. Decussatae. A key to the subseries of E. ser. Subulatae is presented and putative intersubserial, interserial and intersectional hybrids involving the series are cited.
A taxonomic revision and morphological variation within Eucalyptus series Subulatae subseries Spirales (Myrtaceae) of southern Australia
Authors: Nicolle D. , Whalen M. A.
Published: February 2006

Variation in adult and seedling morphology within Eucalyptus series Subulatae subseries Spirales, a group of mallee and woodland tree taxa distributed across southern Australia, was examined. A total of 35 adult morphological characters and 13 seedling characters was included in the phenetic analyses of 150 individuals representing 40 populations covering all the taxa and the broad geographical distribution of the subseries and also including E. brockwayi and E. salmonophloia for comparative purposes. Based on phenetic analyses of adult and seedling characters, six taxa are recognised within E. subser. Spirales and seedling characters are important in delimiting these taxa. Of the seven subspecies of E. oleosa described by Johnson and Hill (1999), two subspecies, E. oleosa subsp. oleosa and subsp. repleta could not be distinguished from one another based on either adult or seedling morphology. Similarly, the three subspecies, E. oleosa subsp. ampliata, wylieana and victima, could not be distinguished. A new taxonomy for E. subser. Spirales based on phenetic analyses combined with extensive field, glasshouse and herbarium examination of all taxa in the subseries is presented. Six terminal taxa in the subseries are recognised, viz. E. delicata, E. longicornis and E. oleosa with subspp. oleosa, ampliata, corvina and cylindroidea. Within E. oleosa, E.oleosa subsp. oleosa and subsp. ampliata are not readily distinguishable on the basis of adult morphology alone. Eucalyptus oleosa subsp. repleta is synonymised with subsp. oleosa, and E. oleosa subspp. wylieana and victima with subsp. ampliata. Keys to the taxa of the subseries are presented.
Dietary risk factors for the emergence of type 1 diabetes-related autoantibodies in 2½-year-old Swedish children
Authors: Wahlberg Jeanette , Vaarala Outi , Ludvigsson Johnny ,   the ABIS-study group
Published: February 2006

We studied dietary risk factors by analysing a questionnaire administered at birth, 1 year and 2½ years of age, as well as the level of glutamic acid decarboxylase autoantibodies (GADA) and tyrosine phosphatase autoantibodies (IA-2A), in 7208 2½-year-old children from the All Babies in Southeast Sweden cohort, using the 95th percentile cut-off for autoantibodies to identify children at risk of type 1 diabetes. A total of 657 children had either IA-2A (n 360) or GADA (n 335), and thirty-eight children had both GADA and IA-2A. In univariate analysis, male gender and maternal coeliac disease implied a risk of possessing IA-2A. Maternal type 2 diabetes, a high consumption of fresh cows milk at the age of 1 year and a late introduction of gluten were associated with a risk of GADA. Early cessation of breast-feeding (≤2 months of age) was associated with a risk of the simultaneous occurrence of both IA-2A and GADA. In logistic regression analysis, a high consumption of milk at the age of 1 year (odds ratio 2·6) represented a risk for GADA, and maternal coeliac disease (odds ratio 2·9) represented a risk for IA-2A. The combination of an early introduction of cows milk formula and a late introduction of gluten-containing food gave an odds ratio of 6·0 for positivity for at least one autoantibody at 1 and 2½ years of age. The induction of autoantibodies by the age of 2½ years has a male preponderance and is more common in children with maternal type 2 diabetes or maternal coeliac disease. Dietary risk factors for the induction of β-cell autoantibodies in 2½-year-old children are a short duration of breast-feeding, an early introduction of cows milk formula and a late introduction of gluten, as well as a high consumption of milk at the age of 1 year.
Effects of supplemental cystine or methionine on growth and lifespan of stroke-prone spontaneously hypertensive rats
Authors: Gilani G. Sarwar , Ratnayake W. M. Nimal , Peace Robert W. , Muller Rudolf
Published: February 2006

Stroke-prone spontaneously hypertensive (SHRSP) rats are considered a suitable model for studying the effects of dietary and other environmental factors on human essential hypertension and haemorrhagic stroke. To investigate the suitability of a control diet for this strain of rats, we studied the effects of supplementing casein and soya protein isolate (SPI) with two sulphur amino acids (methionine and cystine) on the growth and lifespan of SHRSP rats. The source of dietary protein and the type of supplemental sulphur amino acid had significant (P<0·05) effects on food intake and weight gain measured after 31d of the feeding study, while only the type of supplemental sulphur amino acid had significant effects on mean survival times and the survival rates. On average, the casein groups had higher food intake and weight gain compared with the SPI groups. The methionine-supplemented groups had lower food intake but higher weight gain than the cystine-supplemented groups. Similarly, the methionine-supplemented groups had higher mean survival times and survival rates compared with the cystine-supplemented groups. The data would suggest that a control diet based on cystine-supplemented casein (as recommended for normal healthy rats by the American Institute of Nutrition), may not meet the sulphur amino acid requirements for SHRSP rats, and that the methionine-supplemented casein would be an appropriate control diet for this animal model.
Recycling of ESCRTs by the AAA-ATPase Vps4 is regulated by a conserved VSL region in Vta1
Authors: Azmi Ishara , Davies Brian , Dimaano Christian , Payne Johanna , Eckert Debra , Babst Markus , Katzmann David J.
Published: February 2006

In eukaryotes, the multivesicular body (MVB) sorting pathway plays an essential role in regulating cell surface protein composition, thereby impacting numerous cellular functions. Vps4, an ATPase associated with a variety of cellular activities, is required late in the MVB sorting reaction to dissociate the endosomal sorting complex required for transport (ESCRT), a requisite for proper function of this pathway. However, regulation of Vps4 function is not understood. We characterize Vta1 as a positive regulator of Vps4 both in vivo and in vitro. Vta1 promotes proper assembly of Vps4 and stimulates its ATPase activity through the conserved Vta1/SBP1/LIP5 region present in Vta1 homologues across evolution, including human SBP1 and Arabidopsis thaliana LIP5. These results suggest an evolutionarily conserved mechanism through which the disassembly of the ESCRT proteins, and thereby MVB sorting, is regulated by the Vta1/SBP1/LIP5 proteins.
Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway
Authors: Yamamoto Ai , Cremona M. Laura , Rothman James E.
Published: February 2006

Conditional mouse models of polyglutamine diseases, such as Huntington's disease (HD), have revealed that cells can clear accumulated pathogenic proteins if the continuous production of the mutant transgene is halted. Invariably, the clearance of the protein leads to regression of the disease symptoms in mice. In light of these findings, it is critical to determine the pathway responsible for alleviating this protein accumulation to define targets to fight these diseases. In a functional genetic screen of HD, we found that activation of insulin receptor substrate-2, which mediates the signaling cascades of insulin and insulin-like growth factor 1, leads to a macroautophagy-mediated clearance of the accumulated proteins. The macroautophagy is triggered despite activation of Akt, mammalian target of rapamycin (mTOR), and S6 kinase, but still requires proteins previously implicated in macroautophagy, such as Beclin1 and hVps34. These findings indicate that the accumulation of mutant protein can lead to mTOR-independent macroautophagy and that lysosome-mediated degradation of accumulated protein differs from degradation under conditions of starvation.
Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function
Authors: Varma Dileep , Dujardin Denis L. , Stehman Stephanie A. , Vallee Richard B.
Published: February 2006

Zeste white 10 (ZW10) is a mitotic checkpoint protein and the anchor for cytoplasmic dynein at mitotic kinetochores, though it is expressed throughout the cell cycle. We find that ZW10 localizes to pericentriolar membranous structures during interphase and cosediments with Golgi membranes. Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) caused Golgi dispersal. ZW10 RNAi also dispersed endosomes and lysosomes. Live imaging of Golgi, endosomal, and lysosomal markers after reduced ZW10 expression showed a specific decrease in the frequency of minus end–directed movements. Golgi membrane–associated dynein was markedly decreased, suggesting a role for ZW10 in dynein cargo binding during interphase. We also find ZW10 enriched at the leading edge of migrating fibroblasts, suggesting that ZW10 serves as a general regulator of dynein function throughout the cell cycle.
Genetic ablation of zyxin causes Mena/VASP mislocalization, increased motility, and deficits in actin remodeling
Authors: Hoffman Laura M. , Jensen Christopher C. , Kloeker Susanne , Wang C.-L. Albert , Yoshigi Masaaki , Beckerle Mary C.
Published: February 2006

Focal adhesions are specialized regions of the cell surface where integrin receptors and associated proteins link the extracellular matrix to the actin cytoskeleton. To define the cellular role of the focal adhesion protein zyxin, we characterized the phenotype of fibroblasts in which the zyxin gene was deleted by homologous recombination. Zyxin-null fibroblasts display enhanced integrin-dependent adhesion and are more migratory than wild-type fibroblasts, displaying reduced dependence on extracellular matrix cues. We identified differences in the profiles of 75- and 80-kD tyrosine-phosphorylated proteins in the zyxin-null cells. Tandem array mass spectrometry identified both modified proteins as isoforms of the actomyosin regulator caldesmon, a protein known to influence contractility, stress fiber formation, and motility. Zyxin-null fibroblasts also show deficits in actin stress fiber remodeling and exhibit changes in the molecular composition of focal adhesions, most notably by severely reduced accumulation of Ena/VASP proteins. We postulate that zyxin cooperates with Ena/VASP proteins and caldesmon to influence integrin-dependent cell motility and actin stress fiber remodeling.
Time-Dependent Block and Resurgent Tail Currents Induced by Mouse β4154–167 Peptide in Cardiac Na+ Channels
Authors: Wang Ging Kuo , Edrich Thomas , Wang Sho-Ya
Published: February 2006

Resurgent tail Na+ currents were first discovered in cerebellar Purkinje neurons. A recent study showed that a 14-mer fragment of a mouse β4 subunit, β4154–167, acts as an intracellular open-channel blocker and elicits resurgent currents in Purkinje neurons (Grieco, T.M., J.D. Malhotra, C. Chen, L.L. Isom, and I.M. Raman. 2005. Neuron. 45:233–244). To explore these phenotypes in vitro, we characterized β4154–167 actions in inactivation-deficient cardiac hNav1.5 Na+ channels expressed in human embryonic kidney 293t cells. Intracellular β4154–167 from 25–250 μM elicited a conspicuous time-dependent block of inactivation-deficient Na+ currents at 50 mV in a concentration-dependent manner. On and off rates for β4154–167 binding were estimated at 10.1 μM−1s−1 and 49.1 s−1, respectively. Upon repolarization, large tail currents emerged with a slight delay at −140 mV, probably as a result of the rapid unblocking of β4154–167. Near the activation threshold (approximately −70 mV), resurgent tail currents were robust and long lasting. Likewise, β4154–167 induces resurgent currents in wild-type hNav1.5 Na+ channels, although to a lesser extent. The inactivation peptide acetyl-KIFMK-amide not only restored the fast inactivation phenotype in hNav1.5 inactivation-deficient Na+ channels but also elicited robust resurgent currents. When modified by batrachotoxin (BTX), wild-type hNav1.5 Na+ channels opened persistently but became resistant to β4154–167 and acetyl-KIFMK-amide block. Finally, a lysine substitution of a phenylalanine residue at D4S6, F1760, which forms a part of receptors for local anesthetics and BTX, rendered cardiac Na+ channels resistant to β4154–167. Together, our in vitro studies identify a putative S6-binding site for β4154–167 within the inner cavity of hNav1.5 Na+ channels. Such an S6 receptor readily explains (1) why β4154–167 gains access to its receptor as an open-channel blocker, (2), why bound β4154–167 briefly prevents the activation gate from closing by a “foot-in-the-door” mechanism during deactivation, (3) why BTX inhibits β4154–167 binding by physical exclusion, and (4) why a lysine substitution of residue F1760 eliminates β4154–167 binding.
Role of Charged Residues in the S1–S4 Voltage Sensor of BK Channels
Authors: Ma Zhongming , Lou Xing Jian , Horrigan Frank T.
Published: February 2006

The activation of large conductance Ca2+-activated (BK) potassium channels is weakly voltage dependent compared to Shaker and other voltage-gated K+ (KV) channels. Yet BK and KV channels share many conserved charged residues in transmembrane segments S1–S4. We mutated these residues individually in mSlo1 BK channels to determine their role in voltage gating, and characterized the voltage dependence of steady-state activation (Po) and IK kinetics (τ(IK)) over an extended voltage range in 0–50 μM [Ca2+]i. mSlo1 contains several positively charged arginines in S4, but only one (R213) together with residues in S2 (D153, R167) and S3 (D186) are potentially voltage sensing based on the ability of charge-altering mutations to reduce the maximal voltage dependence of PO. The voltage dependence of PO and τ(IK) at extreme negative potentials was also reduced, implying that the closed–open conformational change and voltage sensor activation share a common source of gating charge. Although the position of charged residues in the BK and KV channel sequence appears conserved, the distribution of voltage-sensing residues is not. Thus the weak voltage dependence of BK channel activation does not merely reflect a lack of charge but likely differences with respect to KV channels in the position and movement of charged residues within the electric field. Although mutation of most sites in S1–S4 did not reduce gating charge, they often altered the equilibrium constant for voltage sensor activation. In particular, neutralization of R207 or R210 in S4 stabilizes the activated state by 3–7 kcal mol−1, indicating a strong contribution of non–voltage-sensing residues to channel function, consistent with their participation in state-dependent salt bridge interactions. Mutations in S4 and S3 (R210E, D186A, and E180A) also unexpectedly weakened the allosteric coupling of voltage sensor activation to channel opening. The implications of our findings for BK channel voltage gating and general mechanisms of voltage sensor activation are discussed.
Upregulation of Prostaglandin E2and Interleukins in the Central Nervous System and Peripheral Tissue during and after Surgery in Humans
Authors: Buvanendran Asokumar , Kroin Jeffrey S. , Berger Richard A. , Hallab Nadim J. , Saha Chiranjeev , Negrescu Corina , Moric Mario , Caicedo Marco S. , Tuman Kenneth J.
Published: February 2006

Background

The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E2 and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement.

Methods

Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision.

Results

Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E2 concentration after surgery; interleukin 1beta and tumor necrosis factor alpha were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1beta; tumor necrosis factor alpha decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E2.

Conclusions

These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.
Multifactorial Preoperative Predictors for Postcesarean Section Pain and Analgesic Requirement
Authors: Pan Peter H. , Coghill Robert , Houle Timothy T. , Seid Melvin H. , Lindel W Michael , Parker R Lamar , Washburn Scott A. , Harris Lynne , Eisenach James C.
Published: February 2006

Background

The study aimed to determine predictive factors for postcesarean pain and analgesia using an assessment of pain threshold and suprathreshold thermal stimuli as well as degree of somatization and anxiety.

Methods

Thirty-four healthy parturients scheduled for cesarean delivery under subarachnoid anesthesia were enrolled. Preoperative thermal pain threshold, intensity, and unpleasantness to heat stimuli applied to arm and lower back, State Trait Anxiety Inventory, and patient expectation for postoperative pain and need for analgesia were assessed. After surgery, overall, resting, and movement pain and analgesic consumption were recorded. Prediction of pain and analgesic use outcomes was made by principal component factor analysis, followed by stepwise linear regression.

Results

Resting pain was predicted by two factors, thermal pain and unpleasantness and patient expectation (r2 = 0.26, P < 0.01), evoked pain by thermal pain threshold in the back (r2= 0.20, P < 0.009), composite pain by thermal pain and unpleasantness and preoperative blood pressure (r2 = 0.28, P < 0.008), intraoperative analgesic need by preexisting pain (r2 = 0.22, P < 0.006), recovery room analgesia by thermal pain threshold and State Trait Anxiety Inventory (r2 = 0.27, P < 0.01), and total analgesic need by State Trait Anxiety Inventory (r2 = 0.22, P < 0.01). These models predicted the upper twentieth percentile of composite pain scores and analgesic requirement with sensitivity of 0.71 to 0.80 and specificity of 0.76 to 0.80.

Conclusions

The authors' results suggest a meaningful combination of preoperative patient responses from physical and psychological tests yields a valid multifactorial predictive model for postoperative pain and analgesic requirement with significant improvements over individual predictive variables.
Feasibility and Safety of Delivering Xenon to Patients Undergoing Coronary Artery Bypass Graft Surgery While on Cardiopulmonary Bypass
Authors: Lockwood Geoffrey G. , Franks Nicholas P. , Downie Neil A. , Taylor Kenneth M. , Maze Mervyn
Published: February 2006

Background

Postoperative neurocognitive deficit is prevalent after cardiac surgery. Xenon may prevent or ameliorate acute neuronal injury, but it also may aggravate injury during cardiac surgery by increasing bubble embolism. Before embarking on a randomized clinical trial to test the safety and efficacy of xenon for postoperative neurocognitive deficit, we undertook a phase I study to investigate the safety of administering xenon to patients undergoing coronary artery bypass grafting while on cardiopulmonary bypass and to assess the practicability of our xenon delivery system.

Methods

Sixteen patients scheduled for coronary artery bypass grafting surgery with hypothermic cardiopulmonary bypass gave their informed consent to participate in an open-label dose-escalation study (0, 20, 35, 50% xenon in oxygen and air). Xenon was delivered throughout surgery using both a standard anesthetic breathing circuit and the oxygenator. Gaseous and blood xenon partial pressures were measured five times before, during, and after cardiopulmonary bypass. Middle cerebral artery Doppler was used to assess embolic load, and major organ system function was assessed before and after surgery.

Results

Middle cerebral artery Doppler showed no evidence of increased emboli with xenon. Patients receiving xenon had no major organ dysfunction: Troponin I and S100beta levels tended to be lower in patients receiving xenon. Up to 25 l xenon was used per patient. Xenon partial pressure in the blood tracked the delivered concentration throughout.

Conclusions

Xenon was safely and efficiently delivered to coronary artery bypass grafting patients while on cardiopulmonary bypass. Prevention of nervous system injury by xenon should be tested in a large placebo-controlled, randomized clinical trial.
Comparison of Minimum Alveolar Concentration between Intravenous Isoflurane Lipid Emulsion and Inhaled Isoflurane in Dogs
Authors: Yang Xiao-Lin , Ma Han-Xiang , Yang Zong-Bin , Liu Ai-Jie , Luo Nan-Fu , Zhang Wen-Sheng , Wang Li , Jiang Xue-Hua , Li Jie , Liu Jin
Published: February 2006

Background

As in inhaled isoflurane anesthesia, when isoflurane lipid emulsion (ILE; 8%, vol/vol) is intravenously administered, the primary elimination route is through the lungs. This study was designed to determine the minimum alveolar concentration (MAC) and the time course of washout of isoflurane for intravenously infused ILE by monitoring end-tidal isoflurane concentration.

Methods

Twelve healthy adult mongrel dogs were assigned randomly to an intravenous anesthesia group with 8% ILE or to an inhalation anesthesia group with isoflurane vapor. An up-and-down method and stimulation of tail clamping were used to determine MAC of 8% ILE by intravenous injection in the intravenous anesthesia group and MAC by the inhaled approach in the inhalation anesthesia group, respectively. Isoflurane concentration and partial pressure in end-tidal gas, femoral arterial blood, and jugular venous blood were measured simultaneously just before each tail clamping and during washout.

Results

The induction time in the intravenous anesthesia group (105 +/- 24 s) was shorter than that in the inhalation anesthesia group (378 +/- 102 s; P < 0.01). MAC of 8% ILE by intravenous injection (1.12 +/- 0.18%) was significantly less than MAC by the inhaled approach (1.38 +/- 0.16%; P < 0.05). No significant difference was found between the two groups in the time course of washout of isoflurane.

Conclusion

The MAC of intravenous anesthesia with 8% ILE was less than that of inhalation anesthesia with isoflurane vapor in dogs.
Time Delay of Index Calculation
Authors: Pilge Stefanie , Zanner Robert , Schneider Gerhard , Blum Jasmin , Kreuzer Matthias , Kochs Eberhard F.
Published: February 2006

Background

On the basis of electroencephalographic analysis, several parameters have been proposed as a measure of the hypnotic component of anesthesia. All currently available indices have different time lags to react to a change in the level of anesthesia. The aim of this study was to determine the latency of three frequently used indices: the Cerebral State Index (Danmeter, Odense, Denmark), the Bispectral Index (Aspect Medical Systems Inc., Newton, MA), and the Narcotrend Index (MonitorTechnik, Bad Bramstedt, Germany).

Methods

Artificially generated signals were used to produce up to 14 constant index values per monitor that indicate "awake state," "general anesthesia," and "deep anesthesia" and smaller steps in between. The authors simulated loss of and return to consciousness by changing between the artificial electroencephalographic signals in a full-step and two stepwise approaches and measured the time necessary to adapt the indices to the particular input signal.

Results

Time delays between 14 and 155 s were found for all indices. These delays were not constant. Results were different for decreasing and increasing values and between the full-step and the stepwise approaches. Calculation time depended on the particular starting and target index value.

Conclusions

The time delays of the tested indices may limit their value in prevention of recall of intraoperative events. Furthermore, different latencies for decreasing and increasing values may indicate a limitation of these monitors for pharmacodynamic studies.