bluuebunny/crossref_metadata_2025 huggingface dataset:
Runoff from heterogeneous small bare catchments during soil surface sealing
Authors: Assouline S. , Mualem Y.
Published: December 2006

The combined effects of areal heterogeneity of the soil hydraulic properties and the surface seal formation dominate the hydrological response of arid and semiarid water catchments. Here these two phenomena were simulated to study their mutual role in runoff generation in small bare catchments. Seal formation during rainfall was simulated applying the dynamic model of Assouline and Mualem (1997). Areal heterogeneity of the soil was represented by a lognormal distribution of the saturated hydraulic conductivity of the initially undisturbed soil, Ks, and by related distributions of the other soil parameters. The runoff hydrograph, at the outlet of a hypothetical bare catchment of 0.5 km2, was calculated using the cell model of Diskin et al. (1984). Two water catchments types, homogeneous and heterogeneous, with two different soil surface states, unsealed (mulched) and ongoing dynamic sealing, were considered. Four spatial organizations of the 10 cells in the heterogeneous catchment, all representing the same discrete distribution of Ks, were studied. Rainfall events of two rainfall intensities, 20 and 40 mm h−1, of different durations ranging from 10 to 120 min, were applied uniformly over the catchments to study the effect of rainfall intensity and duration on runoff characteristics under the different soils and catchments conditions. The state of the soil surface seal was found to be a dominant factor with regard to runoff generation. Relative to the runoff produced in the homogeneous unsealed catchment under a (40 mm h−1, 45 min) rainfall, the runoff was augmented by a factor of 10 during soil surface sealing and still more, by a factor of 20, when the soil surface was already sealed. On a relative basis the impact of soil sealing on runoff is much more important than that of soil heterogeneity. The effect of areal heterogeneity on runoff seems to depend on both the soil surface condition and the rainfall intensity and duration. When the soil is unsealed, the total runoff and the discharge peak are higher for the heterogeneous catchment. When the soil surface undergoes a sealing process, the total runoff and the discharge peak are higher for the heterogeneous catchment for the lower rainfall intensity of 20 mm h−1. For the 40 mm h−1 rainfall the catchment relative response was found to depend on the rainfall duration. A higher peak was obtained in the homogeneous catchment for rainfall durations above 60 min, and more runoff was produced for rainfall durations above 90 min. The spatial pattern of the cell organization in the heterogeneous catchment is an additional factor affecting the hydrological response. The hydrographs corresponding to each of four patterns representing the same areal heterogeneity displayed differences regarding concentration time (which varied between 7 and 28 min), timing of the peak runoff (varying between 77 and 146 min), and the peak discharge (varying between 0.41 and 0.57 m3 s−1).
Water shortages and implied water quality: A contingent valuation study
Authors: Genius Margarita , Tsagarakis Konstantinos P.
Published: December 2006

This paper analyses the extent to which households in an urban area are willing to pay to ensure a fully reliable water supply when the latter induces changes in drinking water quality. The water supply system in the city of Heraklion, Greece, is characterized by periodic water rationing, which is more pronounced in the summer months. The generalized use of cisterns and even water tanks helps residents cope with quantity shortages but has a negative effect on the quality of the water reaching their taps. The results of our contingent valuation show that respondents not affected by shortages and already drinking tap water have a smaller willingness to pay, while positive perceptions on quality have a positive effect.
Ice‐dynamical constraints on the existence and impact of subglacial volcanism on West Antarctic ice sheet stability
Authors: Vogel Stefan W. , Tulaczyk Slawek
Published: December 2006

Subglacial volcanism in West Antarctica may play a crucial role in the dynamics and stability of the West Antarctic Ice Sheet (WAIS). Evidence supporting the existence of an individual subglacial volcanic center (Mt. Casertz) in the upper catchments of Whillans and Kamb Ice Stream (WIS and KIS), comes from a comparison of ice sheet modeling results with measured ice velocities. Lubrication of an area, which otherwise should be frozen to its bed, is best explained by basal melt water generated in the vicinity of Mt. Casertz. The estimated melt water production of Mt. Casertz corresponds to ∼8 % of the total melt water production in the two catchments. This would be sufficient to offset basal freezing in the dormant KIS, relubricating its bed and potentially causing a restart. Near future volcanic activity changes are speculative, but would have far reaching implications on the dynamics and stability of the WAIS requiring further investigation.
Was the 2003 European summer heat wave unusual in a global context?
Authors: Chase Thomas N. , Wolter Klaus , Pielke Roger A. , Rasool Ichtiaque
Published: December 2006

We place the European summer heat wave of 2003 in the context of other extreme summer tropospheric temperature events from 22°N to 80°N since 1979, as well as globally using annual averages. The analysis is performed in terms of standard deviations (SD) exceeded and correlations between regional extremes and temperatures at larger spatial scales. As has been pointed out previously the heat wave was statistically unusual and was a deep tropospheric phenomenon. In this analysis we also find the following. (1) Extreme warm anomalies equally, or more, unusual than the 2003 heat wave occur regularly. (2) Extreme cold anomalies also occur regularly and occasionally exceed the magnitude of the 2003 warm anomaly in terms of the value of SD. (3) There is a correlation between global and hemispheric average temperature and the presence of warm or cold regional anomalies of the same sign (i.e., warmer than average years have more regional heat waves and colder than average years have more cold waves). (4) Natural variability in the form of El Niño and volcanic eruptions appear to be of much greater importance in causing extreme regional temperature anomalies than a simple upward trend in time. Extreme temperature anomalies in the wake of the 1997–98 El Niño were larger than the anomalies seen in summer 2003 both in area affected and SD extremes exceeded. (5) Regression analyses do not provide strong support for the idea that regional heat waves are increasing with time.
Historical solar variability derived from sunspot areas using a FIR model
Authors: Preminger Dora G. , Walton Stephen R.
Published: December 2006

We present new historical reconstructions since 1875 of several parameters of solar variability of interest for climate modeling, including spectral solar irradiance at ultraviolet wavelengths and average magnetic field. The reconstructions are based on our Finite Impulse Response (FIR) model, presented in previous work, which establishes the detailed relationship between observed solar variability and sunspots. This model predicts very little long‐term secular trend in the level of solar minimum for any of the reconstructed solar parameters. Cycle‐averaged spectral solar irradiance at ultraviolet and extreme ultraviolet wavelengths increases by about 3% and 20%, respectively, during the first half of the twentieth century. The corresponding cycle‐averaged change in the average magnetic field is about 50%. We estimate that from the Maunder Minimum to the present, the cycle‐averaged increase is about 4% for the irradiance at 200 nm, 30% for the irradiance at 121.6 nm and 100% for the average magnetic field.
Coral reefs reduce tsunami impact in model simulations
Authors: Kunkel Catherine M. , Hallberg Robert W. , Oppenheimer Michael
Published: December 2006

Significant buffering of the impact of tsunamis by coral reefs is suggested by limited observations and some anecdotal reports, particularly following the 2004 Indian Ocean tsunami. Here we simulate tsunami run‐up on idealized topographies in one and two dimensions using a nonlinear shallow water model and show that a sufficiently wide barrier reef within a meter or two of the surface reduces run‐up on land on the order of 50%. We studied topographies representative of volcanic islands (islands with no continental shelf) but our conclusions may pertain to other topographies. Effectiveness depends on the amplitude and wavelength of the incident tsunami, as well as the geometry and health of the reef and the offshore distance of the reef. Reducing the threat to reefs from anthropogenic nutrients, sedimentation, fishing practices, channel‐building, and global warming would help to protect some islands against tsunamis.
Source and consequences of a large shock near 79 AU
Authors: Richardson J. D. , Liu Y. , Wang C. , McComas D. J. , Stone E. C. , Cummings A. C. , Burlaga L. F. , Acuna M. H. , Ness N. F.
Published: December 2006

In March 2006, Voyager 2 (V2) observed a large interplanetary (IP) shock near 79 AU followed by a merged interaction region (MIR). This shock is comparable to the shock observed by V2 at 65 AU in October 2001; these two shocks are the largest observed by V2 since 1991 when V2 was at 35 AU. This shock provides the first opportunity to compare the plasma structure in an IP shock and MIR with the energetic particle fluxes in the termination shock (TS) foreshock region. The flux of >0.5 MeV particles observed by V2 decreased after the shock; the shock and MIR probably pushed the TS outward so that the foreshock region moved outside the distance of V2. The >70 MeV cosmic ray ions decreased in the MIR, probably due to the reduced inward transport caused by the enhanced magnetic field. We model two possible sources of this shock, fast streams from polar coronal holes and coronal mass ejections (CMEs); these sources, when combined, provide a reasonable match to the V2 data.
Ground deformation due to magma ascent with and without degassing
Authors: Nishimura Takeshi
Published: December 2006

I numerically calculate upward migration of vesiculated magma in an elastic volcanic conduit, taking into account the bubble growth in melt, elastic stress from the surrounding medium, and degassing from the magma. The results show that when magma containing gas bubbles reaches the ground surface without degassing, the ground deformation accelerates just before the eruption in response to volumetric expansion of the magma. On the other hand, the rate of change in ground deformation is almost constant when the magma degasses as it ascends. Similar characteristics have been observed in ground deformation recorded before explosive eruptions and lava extrusion at several active volcanoes. These consistencies strongly suggest that geodetic measurements, which have been mainly used to date to estimate the eruption time and the locations of magmatic intrusions, provide a basis for predicting the volcanic explosivity and monitoring bubble growth and degassing processes in the conduit.
Seismicity related to heterogeneous structure along the western Nankai trough off Shikoku Island
Authors: Obana Koichiro , Kodaira Shuichi , Kaneda Yoshiyuki
Published: December 2006

Along the western Nankai trough, southwest Japan, heterogeneous crustal structures, such as scattered deep strong reflectors and a subducted topographic high, showed a spatial relationship to along‐trough variation in the coseismic slip during the 1946 Nankai earthquake, which is the most recent of repeated interplate earthquakes of magnitude 8 range in this area. We observed micro earthquakes using a temporary ocean bottom seismograph network off Shikoku Island, western Nankai trough. Near the trough axis off Cape Muroto, earthquakes in the subducting oceanic plate were associated with structures in the oceanic crust and the uppermost mantle of the subducting plate. Beneath the trough landward slope, the observed earthquakes suggest heterogeneous interplate coupling related to the crustal structure variations. The crustal structure variations could affect the interplate coupling during the interseismic period as well as coseismic rupture propagation during large interplate earthquakes along the western Nankai trough.
Controlling effect of the pitch angle scattering rates near the edge of the loss cone on electron lifetimes
Authors: Shprits Y. Y. , Li W. , Thorne R. M.
Published: December 2006

Intense interest currently exists in quantification of the loss of relativistic electrons in the outer radiation belts. Using diffusion coefficients computed for parallel propagating chorus waves, the evolution of the electron pitch angle distribution is examined. Sensitivity numerical experiments show that electron lifetimes are most sensitive to the value of the pitch angle scattering rate near the edge of the loss cone. When the scattering rates do not drop by more than an order of magnitude of the value near the edge of the loss cone for a 30 degree range of pitch angles, we find that the pitch angle distribution reaches an equilibrium shape within hours of the simulations and then decays exponentially with the same rate at all equatorial pitch angles. Implications of the results for combined scattering by EMIC and chorus or hiss waves are discussed as well as implications for future modeling and comparison with observations.
High‐resolution terrestrial nightglow emission line atlas from UVES/VLT: Positions, intensities, and identifications for 2808 lines at 314–1043 nm
Authors: Cosby Philip C. , Sharpee Brian D. , Slanger Tom G. , Huestis David L. , Hanuschik Reinhard W.
Published: December 2006

The atlas of terrestrial nightglow emission lines from spectra of the night sky obtained from the Ultraviolet and Visual Echelle Spectrograph (UVES) on the 8.2‐m UT2 telescope at the Very Large Telescope (VLT), European Southern Observatory, Cerro Paranal, Chile, consists of 2808 line positions, line widths, and intensities over the 314–1043 nm spectral range (Hanuschik, 2003). These lines have been absolute intensity calibrated and measured at a spectral resolution (λ/Δλ) of ∼43,000–45,000. Presented here are spectroscopic identifications for 98% of the lines in the atlas, made primarily through comparisons with synthetic spectra of prominent OH and O2 nightglow emission systems. The ability to simulate these systems successfully has shown that there are many additional lines that could be added to the atlas. We believe that all the O2 and OH lines in the measured region can now be successfully modeled with an accuracy better than the instrumental spectral resolution.
ORILAM‐SOA: A computationally efficient model for predicting secondary organic aerosols in three‐dimensional atmospheric models
Authors: Tulet Pierre , Grini Alf , Griffin Robert J. , Petitcol Sebastien
Published: December 2006

This paper describes the aerosol model Organic Inorganic Lognormal Aerosol Model including Secondary Organic Aerosol (ORILAM‐SOA) which is an extension of the lognormal aerosol dynamics model ORILAM. ORILAM‐SOA consists of the original aerosol dynamics routines, a photochemical scheme able to predict SOA precursors, and an equilibrium scheme able to predict partitioning of the precursors between the gas and aerosol phases. We show that ORILAM‐SOA is computationally efficient enough to be run in three‐dimensional (3‐D) atmospheric models. ORILAM‐SOA is based on existing models. We use a numerical reduction technique to reduce the Caltech Atmospheric Chemistry Mechanism (CACM) and a new, fast, convergent iteration technique to increase the speed of the Model to Predict the Multiphase Partitioning of Organics (MPMPO). We compare the ORILAM‐SOA to its parent models in terms of gas concentrations, aerosol concentrations, and CPU time spent during the computations. For illustrative purposes we include a 3‐D simulation of SOA over southern France.
Variations in K/Th on Mars
Authors: Taylor G. Jeffrey , Stopar J. D. , Boynton W. V. , Karunatillake S. , Keller J. M. , Brückner J. , Wänke H. , Dreibus G. , Kerry K. E. , Reedy R. C. , Evans L. G. , Starr R. D. , Martel L. M. V. , Squyres S. W. , Gasnault O. , Maurice S. , d'Uston C. , Englert P. , Dohm J. M. , Baker V. R. , Hamara D. , Janes D. , Sprague A. L. , Kim K. J. , Drake D. M. , McLennan S. M. , Hahn B. C.
Published: December 2006

K/Th determined by the Mars Odyssey Gamma Ray Spectrometer varies by a factor of 3 on Mars (3000 to 9000), but over 95% of the surface area has K/Th between 4000 and 7000. K/Th is distinctly lower than average in some areas, including west of Olympus Mons in the Amazonis Planitia, the region around Memnonia Fossae, Chryse Planitia, southeastern Arabia Terra, Syrtis Major Planum, and northwest of Apollinaris Patera. On the other hand, K/Th is distinctly higher than average in other areas, including the central part of Valles Marineris and the surrounding highlands, and in the northern part of Hellas. The generally modest variation in K/Th may be explained by inherent variations in igneous rocks and by variations in the extent of aqueous alteration.
Seasonal polar carbon dioxide frost on Mars: CO2 mass and columnar thickness distribution
Authors: Kelly N. J. , Boynton W. V. , Kerry K. , Hamara D. , Janes D. , Reedy R. C. , Kim K. J. , Haberle R. M.
Published: December 2006

Conclusions are drawn about the column density (g/cm2), spatial extent, and mass of the seasonal carbon dioxide frost on the poles of Mars as a function of time utilizing data from the 2001 Mars Odyssey Gamma Ray Spectrometer (GRS). Quantification of these CO2 values is achieved by observing attenuation effects of the surface‐emitted hydrogen gamma ray flux as the frost condenses and sublimates in a seasonal exchange of CO2 between the ground and the atmosphere. Columnar thickness and mass results are discussed and plotted for latitudes including ±60° and poleward. GRS observations are compared to predictions from the NASA Ames Research Center General Circulation Model and to similar experimental results from the Mars Odyssey High Energy Neutron Detector and Neutron Spectrometer. Models for north and south polar atmosphere and regolith distributions are incorporated, and our results indicate that the assumption of a 100% H2O‐ice residual cap underlying the seasonal frost in the north is accurate. The GRS CO2 frost observations are in good agreement with the other studies mentioned, in particular for the timing of the beginning of frost deposition to the complete sublimation of surface CO2 back into the atmosphere. The total amount of condensed carbon dioxide mass seen by the GRS is on the order of 6.0 × 1015 kg and verifies previous reports that nearly 25% of the Martian CO2 reservoir participates in the ground‐atmosphere exchange cycle.
Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells
Authors: Kobori M , Yoshida M , Ohnishi‐Kameyama M , Shinmoto H
Published: December 2006

Background and purpose:

5α,8α‐Epidioxy‐22E‐ergosta‐6, 22‐dien‐3β‐ol (ergosterol peroxide) is a major antitumour sterol produced by edible or medicinal mushrooms. However, its molecular mechanism of action has yet to be determined. Here, we examine the anticancer and anti‐inflammatory effects of ergosterol peroxide.

Experimental approach:

After treating RAW264.7 macrophages with LPS and purified ergosterol peroxide or ergosterol, we determined LPS‐induced inflammatory cytokines, nuclear DNA binding activity of transcription factors and phosphorylation of MAP kinases (MAPKs). HT29 colorectal adenocarcinoma cells were treated with ergosterol peroxide for 5 days. To investigate the antitumour properties of ergosterol peroxide, we performed DNA microarray and RT‐PCR analyses and determined the reactive oxygen species (ROS) in HT29 cells.

Key results:

Ergosterol peroxide suppressed LPS‐induced TNF‐α secretion and IL‐1α/β expression in RAW264.7 cells. Ergosterol peroxide and ergosterol suppressed LPS‐induced DNA binding activity of NF‐κB and C/EBPβ, and inhibited the phosphorylation of p38, JNK and ERK MAPKs. Ergosterol peroxide down‐regulated the expression of low‐density lipoprotein receptor (LDLR) regulated by C/EBP, and HMG‐CoA reductase (HMGCR) in RAW264.7 cells. In addition, ergosterol peroxide showed cytostatic effects on HT29 cells and increased intracellular ROS. Furthermore, ergosterol peroxide induced the expression of oxidative stress‐inducible genes, and the cyclin‐dependent kinase inhibitor CDKN1A, and suppressed STAT1 and interferon‐inducible genes.

Conclusion and Implication:

Our results suggest that ergosterol peroxide and ergosterol suppress LPS‐induced inflammatory responses through inhibition of NF‐κB and C/EBPβ transcriptional activity, and phosphorylation of MAPKs. Moreover, ergosterol peroxide appears to suppress cell growth and STAT1 mediated inflammatory responses by altering the redox state in HT29 cells.

British Journal of Pharmacology (2007) 150, 209–219. doi:10.1038/sj.bjp.0706972
Cyclodextrins sequester neuroactive steroids and differentiate mechanisms that rate limit steroid actions
Authors: Shu H‐J , Zeng C‐M , Wang C , Covey D F , Zorumski C F , Mennerick S
Published: December 2006

Background and purpose:

Neuroactive steroids are potent modulators of GABAAreceptors and are thus of interest for their sedative, anxiolytic, anticonvulsant and anaesthetic properties. Cyclodextrins may be useful tools to manipulate neuroactive effects of steroids on GABAAreceptors because cyclodextrins form inclusion complexes with at least some steroids that are active at the GABAAreceptor, such as (3α,5α)‐3‐hydroxypregnan‐20‐one (3α5αP, allopregnanolone).

Experimental approach:

To assess the versatility of cyclodextrins as steroid modulators, we investigated interactions between γ‐cyclodextrin and neuroactive steroids of different structural classes.

Key results:

Both a bioassay based on electrophysiological assessment of GABAAreceptor function and optical measurements of cellular accumulation of a fluorescent steroid analogue suggest that γ‐cyclodextrin sequesters steroids rather than directly influencing GABAAreceptor function. Neither a 5β‐reduced A/B ring fusion nor a sulphate group at carbon 3 affected the presumed inclusion complex formation between steroid and γ‐cyclodextrin. Apparent dissociation constants for interactions between natural steroids and γ‐cyclodexrin ranged from 10‐60 μM. Although γ‐cyclodextrin accommodates a range of natural and synthetic steroids, C11substitutions reduced inclusion complex formation. Using γ‐cyclodextrin to remove steroid not directly bound to GABAAreceptors, we found that cellular retention of receptor‐unbound steroid rate limits potentiation by 3α‐ hydroxysteroids but not inhibition by sulphated steroids.

Conclusions and implications:

We conclude that γ‐cyclodextrins can be useful, albeit non‐specific, tools for terminating the actions of multiple classes of naturally occurring neuroactive steroids.

British Journal of Pharmacology(2007)150, 164–175. doi:10.1038/sj.bjp.0706973
Immunopathology of schistosomiasis
Authors: Wilson Mark S , Mentink‐Kane Margaret M , Pesce John T , Ramalingam Thirumalai R , Thompson Robert , Wynn Thomas A
Published: December 2006

Waterborne parasitic diseases plague tropical regions of the world with the development of water resources often increasing transmission. Skin‐penetrating cercariae (infectious stages of schistosome parasites) mature within their mammalian host, form sexual pairs and produce several hundred eggs per day. Many eggs are swept within the circulation and in the case of Schistosoma mansoni and S. japonicum, become lodged within hepatic sinusoids, invoking a fibrotic granulomatous response. Animal studies have identified a moderate type 1 helper (Th1) response to parasite antigens; however, a robust Th2 response to egg‐derived antigens dominates and propagates fibrogenesis within the liver. Elegant T helper cell polarization studies have highlighted that critical control of Th1, Th2 and interleukin (IL)‐17‐secreting lymphocytes is necessary to prevent severe liver pathology. Alternatively activated macrophages develop in the Th2 milieu and upregulate Fizz1, Ym‐1 and Arg‐1. The possible contribution of macrophages to fibrogenesis and their role in immune regulation are discussed. Within the liver, natural (CD4+CD25+ Forkhead box protein 3 (Foxp3)+) and inducible (CD4+Foxp3–) Treg's are recruited, providing an essential regulatory arm to stabilize the immune response and limit immunopathology. This review ties together current thinking of how the granulomatous response develops, causing much of the associated immunopathology, with extensive discussions on how regulatory cells and cytokine decoy receptors serve to limit the extent of immune‐mediated pathology during schistosomiasis.
The C-terminus of CIS defines its interaction pattern
Authors: Lavens Delphine , Ulrichts Peter , Catteeuw Dominiek , Gevaert Kris , Vandekerckhove Joël , Peelman Frank , Eyckerman Sven , Tavernier Jan
Published: December 2006

Proteins of the SOCS (suppressors of cytokine signalling) family are characterized by a conserved modular structure with pre-SH2 (Src homology 2), SH2 and SOCS-box domains. Several members, including CIS (cytokine-inducible SH2 protein), SOCS1 and SOCS3, are induced rapidly upon cytokine receptor activation and function in a negative-feedback loop, attenuating signalling at the receptor level. We used a recently developed mammalian two-hybrid system [MAPPIT (mammalian protein–protein interaction trap)] to analyse SOCS protein-interaction patterns in intact cells, allowing direct comparison with biological function. We find that, besides the SH2 domain, the C-terminal part of the CIS SOCS-box is required for functional interaction with the cytokine receptor motifs examined, but not with the N-terminal death domain of the TLR (Toll-like receptor) adaptor MyD88. Mutagenesis revealed that one single tyrosine residue at position 253 is a critical binding determinant. In contrast, substrate binding by the highly related SOCS2 protein, and also by SOCS1 and SOCS3, does not require their SOCS-box.
Differential regulation of human YY1 and caspase 7 promoters by prohibitin through E2F1 and p53 binding sites
Authors: Joshi B. , Rastogi S. , Morris M. , Carastro L. M. , Decook C. , Seto E. , Chellappan S. P.
Published: December 2006

Prohibitin is a 30 kDa growth suppressive protein that has pleiotropic functions in the cell. Although prohibitin has been demonstrated to have potent transcriptional regulatory functions, it has also been proposed to facilitate protein folding in the mitochondria and promote cell migration in association with Raf-1. Our previous studies have shown that prohibitin physically interacts with the marked-box domain of E2F family members and represses their transcriptional activity; in contrast, prohibitin could bind to and enhance the transcriptional activity of p53. Here, we show that promoters of human YY1 (Yin and Yang 1) as well as caspase 7 genes are modulated by prohibitin. YY1 promoter activity was reduced upon overexpression of prohibitin, while it was enhanced when prohibitin was depleted by small interfering RNA techniques. The repressive effects of prohibitin on the YY1 promoter were mediated through E2F binding sites, as seen by mutational analysis and chromatin immunoprecipitation assays. Further, depletion of E2F1 prevented prohibitin from repressing the YY1 promoter. In contrast with YY1, prohibitin overexpression led to enhanced levels of caspase 7, whereas depletion of prohibitin reduced it. Interestingly, the caspase 7 promoter was found to have p53-binding sites and prohibitin activated this promoter through p53. These studies show that prohibitin can have diverse effects on the expression of different genes and the activity of various cellular promoters is affected by prohibitin. Further, it appears very likely that prohibitin carries out many of its cellular functions by affecting the transcription of different genes.
A variably spliced region in the type 1 ryanodine receptor may participate in an inter-domain interaction
Authors: Kimura Takashi , Pace Suzy M. , Wei Lan , Beard Nicole A. , Dirksen Robert T. , Dulhunty Angela F.
Published: December 2006

The aim of the present study was to examine residues that are variably spliced in the juvenile and adult isoforms of the skeletal-muscle RyR1 (type 1 ryanodine receptor). The juvenile ASI(−) splice variant is less active than the adult ASI(+) variant and is overexpressed in patients with DM (myotonic dystrophy) [Kimura, Nakamori, Lueck, Pouliquin, Aoike, Fujimura, Dirksen, Takahashi, Dulhunty and Sakoda (2005) Hum. Mol. Genet. 14, 2189–2200]. In the present study, we explore the ASI region using synthetic peptides corresponding to rabbit RyR1 residues Thr3471-Gly3500 either containing [PASI(+)] or lacking [PASI(−)] the ASI residues. Both peptides increased [3H]ryanodine binding to rabbit RyR1s, increased Ca2+ release from sarcoplasmic reti-culum vesicles and increased single RyR1 channel activity. The peptide PASI(−) was more active in each case than PASI(+). [3H]Ryanodine binding to recombinant ASI(+)RyR1 or ASI(−)-RyR1 was enhanced more by PASI(−) than PASI(+), with the greatest increase seen when PASI(−) was added to ASI(−)RyR1. The activation of the RyR channels is consistent with the hypo-thesis that the peptides interrupt an inhibitory inter-domain inter-action and that PASI(−) is more effective at interrupting this interaction than PASI(+). We therefore suggest that the ASI(−) sequence interacts more tightly than the ASI(+) sequence with its binding partner, so that the ASI(−)RyR1 is more strongly inhibited (less active) than the ASI(+)RyR1. Thus the affinity of the binding partners in this inter-domain interaction may deter-mine the activities of the mature and juvenile isoforms of RyR1 and the stronger inhibition in the juvenile isoform may contribute to the myopathy in DM.
Proteinase-activated receptor-1 and -2 induce the release of chemokine GRO/CINC-1 from rat astrocytes via differential activation of JNK isoforms, evoking multiple protective pathways in brain
Authors: Wang Yingfei , Luo Weibo , Reiser Georg
Published: December 2006

Activation of both PAR-1 (proteinase-activated receptor-1) and PAR-2 resulted in release of the chemokine GRO (growth-regulated oncogene)/CINC-1 (cytokine-induced neutrophil chemoattractant-1), a functional counterpart of human interleukin-8, from rat astrocytes. Here, we investigate whether the two PAR receptor subtypes can signal separately. PAR-2-induced GRO/CINC-1 release was independent of protein kinase C, phosphoinositide 3-kinase and MEK (mitogen-activated protein kinase kinase)-1/2 activation, whereas these three kinases were involved in PAR-1-induced GRO/CINC-1 release. Despite such clear differences between PAR-1 and PAR-2 signalling pathways, JNK (c-Jun N-terminal kinase) was identified in both signalling pathways to play a pivotal role. By isoform-specific loss-of-function studies using small interfering RNA against JNK1–3, we demonstrate that different JNK isoforms mediated GRO/CINC-1 secretion, when it was induced by either PAR-1 or PAR-2 activation. JNK2 and JNK3 isoforms were both activated by PAR-1 and essential for chemokine GRO/CINC-1 secretion, whereas PAR-1-mediated JNK1 activation was mainly responsible for c-Jun phosphorylation, which was not involved in GRO/CINC-1 release. In contrast, PAR-2-induced JNK1 activation, which failed to phosphorylate c-Jun, uniquely contributed to GRO/CINC-1 release. Therefore our results show for the first time that JNK-mediated chemokine GRO/CINC-1 release occurred in a JNK isoform-dependent fashion and invoked PAR subtype-specific mechanisms. Furthermore, here we demonstrate that activation of PAR-2, as well as PAR-1, rescued astrocytes from ceramide-induced apoptosis via regulating chemokine GRO/CINC-1 release. Taken together, our results suggest that PAR-1 and PAR-2 have overlapping functions, but can activate separate pathways under certain pathological conditions to rescue neural cells from cell death. This provides new functional insights into PAR/JNK signalling and the protective actions of PARs in brain.
A new assay for nitric oxide reductase reveals two conserved glutamate residues form the entrance to a proton-conducting channel in the bacterial enzyme
Authors: Thorndycroft Faye H. , Butland Gareth , Richardson David J. , Watmough Nicholas J.
Published: December 2006

A specific amperometric assay was developed for the membrane-bound NOR [NO (nitric oxide) reductase] from the model denitrifying bacterium Paracoccus denitrificans using its natural electron donor, pseudoazurin, as a co-substrate. The method allows the rapid and specific assay of NO reduction catalysed by recombinant NOR expressed in the cytoplasmic membranes of Escherichia coli. The effect on enzyme activity of substituting alanine, aspartate or glutamine for two highly conserved glutamate residues, which lie in a periplasmic facing loop between transmembrane helices III and IV in the catalytic subunit of NOR, was determined using this method. Three of the substitutions (E122A, E125A and E125D) lead to an almost complete loss of NOR activity. Some activity is retained when either Glu122 or Glu125 is substituted with a glutamine residue, but only replacement of Glu122 with an aspartate residue retains a high level of activity. These results are interpreted in terms of these residues forming the mouth of a channel that conducts substrate protons to the active site of NOR during turnover. This channel is also likely to be that responsible in the coupling of proton movement to electron transfer during the oxidation of fully reduced NOR with oxygen [U. Flock, N. J. Watmough and P. Ädelroth (2005) Biochemistry 44, 10711–10719].
Malignant hyperthermia mutation sites in the Leu2442–Pro2477 (DP4) region of RyR1 (ryanodine receptor 1) are clustered in a structurally and functionally definable area
Authors: Bannister Mark L. , Hamada Tomoyo , Murayama Takashi , Harvey Peta J. , Casarotto Marco G. , Dulhunty Angela F. , Ikemoto Noriaki
Published: December 2006

To explain the mechanism of pathogenesis of channel disorder in MH (malignant hyperthermia), we have proposed a model in which tight interactions between the N-terminal and central domains of RyR1 (ryanodine receptor 1) stabilize the closed state of the channel, but mutation in these domains weakens the interdomain interaction and destabilizes the channel. DP4 (domain peptide 4), a peptide corresponding to residues Leu2442–Pro2477 of the central domain, also weakens the domain interaction and produces MH-like channel destabilization, whereas an MH mutation (R2458C) in DP4 abolishes these effects. Thus DP4 and its mutants serve as excellent tools for structure–function studies. Other MH mutations have been reported in the literature involving three other amino acid residues in the DP4 region (Arg2452, Ile2453 and Arg2454). In the present paper we investigated the activity of several mutants of DP4 at these three residues. The ability to activate ryanodine binding or to effect Ca2+ release was severely diminished for each of the MH mutants. Other substitutions were less effective. Structural studies, using NMR analysis, revealed that the peptide has two α-helical regions. It is apparent that the MH mutations are clustered at the C-terminal end of the first helix. The data in the present paper indicates that mutation of residues in this region disrupts the interdomain interactions that stabilize the closed state of the channel.
Mimicking phosphorylation of αB-crystallin affects its chaperone activity
Authors: Ecroyd Heath , Meehan Sarah , Horwitz Joseph , Aquilina J. Andrew , Benesch Justin L. P. , Robinson Carol V. , Macphee Cait E. , Carver John A.
Published: December 2006

αB-crystallin is a member of the sHsp (small heat-shock protein) family that prevents misfolded target proteins from aggregating and precipitating. Phosphorylation at three serine residues (Ser19, Ser45 and Ser59) is a major post-translational modification that occurs to αB-crystallin. In the present study, we produced recombi-nant proteins designed to mimic phosphorylation of αB-crystallin by incorporating a negative charge at these sites. We employed these mimics to undertake a mechanistic and structural invest-igation of the effect of phosphorylation on the chaperone activity of αB-crystallin to protect against two types of protein misfolding, i.e. amorphous aggregation and amyloid fibril assembly. We show that mimicking phosphorylation of αB-crystallin results in more efficient chaperone activity against both heat-induced and reduc-tion-induced amorphous aggregation of target proteins. Mimick-ing phosphorylation increased the chaperone activity of αB-crystallin against one amyloid-forming target protein (κ-casein), but decreased it against another (ccβ-Trp peptide). We observed that both target protein identity and solution (buffer) conditions are critical factors in determining the relative chaperone ability of wild-type and phosphorylated αB-crystallins. The present study provides evidence for the regulation of the chaperone activity of αB-crystallin by phosphorylation and indicates that this may play an important role in alleviating the pathogenic effects associated with protein conformational diseases.
HBx-dependent cell cycle deregulation involves interaction with cyclin E/A–cdk2 complex and destabilization of p27Kip1
Authors: Mukherji Atish , Janbandhu Vaibhao C. , Kumar Vijay
Published: December 2006

The HBx (X protein of hepatitis B virus) is a promiscuous transactivator implicated to play a key role in hepatocellular carcinoma. However, HBx-regulated molecular events leading to deregulation of cell cycle or establishment of a permissive environment for hepatocarcinogenesis are not fully understood. Our cell culture-based studies suggested that HBx had a profound effect on cell cycle progression even in the absence of serum. HBx presence led to an early and sustained level of cyclin–cdk2 complex during the cell cycle combined with increased protein kinase activity of cdk2 heralding an early proliferative signal. The increased cdk2 activity also led to an early proteasomal degradation of p27Kip1 that could be reversed by HBx-specific RNA interference and blocked by a chemical inhibitor of cdk2 or the T187A mutant of p27. Further, our co-immunoprecipitation and in vitro binding studies with recombinant proteins suggested a direct interaction between HBx and the cyclin E/A–cdk2 complex. Interference with different signalling cascades known to be activated by HBx suggested a constitutive requirement of Src kinases for the association of HBx with these complexes. Notably, the HBx mutant that did not interact with cyclin E/A failed to destabilize p27Kip1 or deregulate the cell cycle. Thus HBx appears to deregulate the cell cycle by interacting with the key cell cycle regulators independent of its well-established role in transactivation.
Yeast sphingolipids do not need to contain very long chain fatty acids
Authors: Cerantola Vanessa , Vionnet Christine , Aebischer Olivier F. , Jenny Titus , Knudsen Jens , Conzelmann Andreas
Published: December 2006

Synthesis of VLCFAs (very long chain fatty acids) and biosynthesis of DHS (dihydrosphingosine) both are of vital importance for Saccharomyces cerevisiae. The bulk of VLCFAs and DHS are used for ceramide synthesis by the Lag1p (longevity-assurance gene 1)/Lac1p (longevity-assurance gene cognate 1)/Lip1p (Lag1p/Lac1p interacting protein) ceramide synthase. LAG1 and LAC1 are redundant but LIP1 is essential. Here we show that 4Δ (lag1Δlac1Δypc1Δydc1Δ) cells devoid of all known endogenous ceramide synthesis pathways are unviable but can be rescued by the expression of Lass5, a mouse LAG1 homologue. Ceramide synthase activity of 4Δ.Lass5 cells only utilizes C16 and C18 fatty acids and does not require the help of Lip1p, an essential cofactor of Lag1p/Lac1p. HPLC-electrospray ionization-MS/MS analysis demonstrated that in IPCs (inositolphosphorylceramides) of 4Δ.Lass5, the very long chain fatty acids (C26 and C24) account for <1% instead of the normal >97%. Notwithstanding, IPCs incorporated into glycosylphosphatidylinositol anchors of 4Δ.Lass5 show normal mobility on TLC and the ceramide- and raft-dependent traffic of Gas1p (glycophospholipid-anchored surface protein) from endoplasmic reticulum to Golgi remains almost normal. Moreover, the biosynthesis of C24:0 fatty acids remains essential. Thus, C24:0 and dihydrosphingosine are both necessary for survival of yeast cells even if they utilize C16 and C18 fatty acids for sphingolipid biosynthesis.
Cardiac mitochondrial cGMP stimulates cytochrome c release
Authors: Seya Kazuhiko , Motomura Shigeru , Furukawa Ken-Ichi
Published: December 2006

Although the existence of cardiac mitochondrial cGMP has been reported previously [Kimura and Murad (1974) J. Biol. Chem. 249, 6910–6916], the physiological and pathophysiological properties of cGMP in cardiac mitochondria have remained unknown. The aim of the present study was to clarify whether cardiac mitochondrial cGMP regulates the apoptosis of cardiomyocytes. In the presence of GTP, the NO donors SNAP (S-nitroso-N-acetyl-DL-penicillamine; 1 mmol/l) and SNP (sodium nitroprusside; 1 mmol/l) each markedly increased the cGMP level in a highly purified mitochondrial protein fraction prepared from left ventricular myocytes of male Wistar rats, and these increases were inhibited by 1 μmol/l ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), an inhibitor of NO-sensitive guanylate cyclase. In purified mitochondria, both SNAP (1 mmol/l) and the membrane-permeant cGMP analogue 8-Br-cGMP (8-bromo-cGMP; 1 mmol/l), but not cGMP (1 mmol/l), increased cytochrome c release from succinate-energized mitochondria without inducing mitochondrial swelling and depolarization of the mitochondrial membrane as factors of activation of MPT (mitochondrial permeability transition). The cytochrome c release mediated by SNAP was inhibited in the presence of 1 μmol/l ODQ. On the other hand, 1 mmol/l SNAP induced apoptosis in primary cultured adult rat cardiomyocytes in a time-dependent manner, and this induction was significantly inhibited in the presence of ODQ. Furthermore, apoptosis induced in primary cultured cardiomyocytes by hypoxia/re-oxygenation was also inhibited by ODQ. These results suggest that the acceleration of cGMP production in cardiac mitochondria stimulates cytochrome c release from mitochondria in an MPT-independent manner, resulting in apoptosis.
Fatty liver is an integral feature of familial combined hyperlipidaemia: relationship with fat distribution and plasma lipids
Authors: Brouwers Martijn C. G. J. , Bilderbeek-Beckers Monique A. L. , Georgieva Anna M. , van der Kallen Carla J. H. , van Greevenbroek Marleen M. J. , de Bruin Tjerk W. A.
Published: December 2006

Overproduction of VLDL (very-low-density lipoprotein) particles is an important cause of FCHL (familial combined hyperlipidaemia). It has been shown recently that VLDL production is driven by the amount of hepatic fat. The present study was conducted to determine the prevalence of fatty liver in relation to the different fat compartments and lipid parameters in FCHL. A total of 68 FCHL patients, 110 normolipidaemic relatives and 66 spouses underwent ultrasound of the abdominal region to estimate the amount of subcutaneous, visceral and hepatic fat. Skinfold callipers were used to measure subcutaneous fat of the biceps, triceps, subscapular and supra-iliacal regions. Fatty liver was observed in 18% of the spouses, 25% of the normolipidaemic relatives and 49% of the FCHL patients. After adjustment for age, gender and body mass index, the prevalence of fatty liver was significantly higher in FCHL patients compared with spouses [OR (odds ratio), 3.1; P=0.03], and also in the normolipidaemic relatives compared with spouses (OR, 4.0; P=0.02), whereas no differences were observed between FCHL patients and normolipidaemic relatives (OR, 0.8; P=0.58). In the normolipidaemic relatives and FCHL patients combined, both visceral fat mass and subcutaneous abdominal fat were independent predictors of fatty liver (P<0.001 for both fat compartments; FCHL status corrected). Of interest, fatty liver stages were correlated with both VLDL-apoB (apolipoprotein B) and VLDL-triacylglycerols (triglycerides) in a representative subset (n=69) of patients and relatives (r2=0.12, P=0.006; and r2=0.18, P=0.001 respectively). These results show that fatty liver is a central aspect of FCHL, i.e. patients and normolipidaemic relatives. Both visceral and subcutaneous adiposity contribute to its 3–4-fold higher risk in FCHL.
Numerical simulation of isotope production for positron emission tomography with laser-accelerated ions
Authors: Lefebvre Erik , d’Humières Emmanuel , Fritzler Sven , Malka Victor
Published: December 2006

The experimental demonstration of laser acceleration of ions to multi-MeV energies with short, intense laser pulses has spurred the prospect of using this ion source for medical isotope production. Using numerical models for laser-plasma interaction and ion acceleration, then for ion transport and isotope production, we compute the isotope yields that could be expected from such sources, and their variations with interaction parameters such as target thickness and laser intensity. Using 36fs, 4×1020W∕cm2 pulses at kilohertz repetition rate, more than 100GBq of F18 are expected after irradiation for 1h.
Anisotropic magnetoresistance of La0.7Ca0.3MnO3 thin film biepitaxial step junctions
Authors: Chen S. F. , Chang W. J. , Hsieh C. C. , Liu S. J. , Juang J. Y. , Wu K. H. , Uen T. M. , Lin J.-Y. , Gou Y. S.
Published: December 2006

The angular dependence of magnetoresistance (MR) of the La0.7Ca0.3MnO3 thin film biepitaxial step junction (BSJ) shows a simple sin2(θ) dependence in the in-plane high-field magnetoresistance, with θ being the angle between the applied field and current. This behavior is similar to the spin-orbit coupling-induced anisotropic magnetoresistance (AMR) commonly observed in transition ferromagnetic metals, except for two salient features. First, the maximum MR in the present case occurs at an oblique angle between the applied field (H) and electric current (I), while it is usually observed to occur when H‖I. Second, the AMR in the plane perpendicular to the film surface displays a remarkable value (Δρ∕ρ∼8%), which is about an order of magnitude larger than that of the in-plane AMR. Such a large AMR cannot be solely explained by spin-orbit coupling effect. We suggest instead that the metallic and ferromagnetic inhomogeneous granules existing in the BSJ region might have acted as the source of spin-polarized scattering giving rise to the enhanced AMR when the colossal magnetoresistance was measured across the biepitaxial step boundaries.
Influence of submonolayer sodium adsorption on the photoemission of the Cu(111)/water ice surface
Authors: Vondrak Tomas , Plane John M. C. , Meech Stephen R.
Published: December 2006

Photoemission from an ice film deposited on Cu(111) as a function of thickness has been observed in the presence and absence of sodium atoms at the surface-vacuum interface. For either adsorbate alone and photon energies below 4eV, two-photon photoemission from the Cu(111) substrate dominates. The Cu(111) photoelectron spectrum is perturbed by low coverages of Na, and its intensity is strongly attenuated by a few monolayers of ice. For a low density amorphous ice film, strong charging effects are observed. For ice films annealed to yield either the dense amorphous or crystalline phase, this effect is absent. Deposition of only 0.02 monolayer of Na leads to a dramatic decrease in the threshold for photoemission to 2.3±0.2eV. Thus, photoelectrons are generated by visible radiation in a one-photon process with a cross section that exceeds 10−18cm2. The initial state for the photoemission is identified as a metastable surface trapped electron, which decays thermally with an activation energy of 10±2kJmol−1. Quantum calculations are described which support this model and show that the Na atom is accommodated in the first layer of the ice surface.