bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulated changes in the extratropical Southern Hemisphere winds and currents
Authors: Fyfe John C. , Saenko Oleg A.
Published: March 2006

The results from 12 global climate models show a remarkably consistent strengthening and poleward shifting of the zonal wind stress through the 20th and 21st centuries at extratropical Southern Hemisphere latitudes. Changes in the zonal circulation of the ocean in the region are broadly consistent with the changes in zonal wind stress. In particular, the climate models simulate a strengthening and a poleward shift of the Antarctic Circumpolar Current. The strengthening of the zonal wind stress also results in intensifying northward Ekman transport across the Antarctic Circumpolar Current which, in the unblocked latitudes of Drake Passage, implies increasing southward geostrophic transport in the ocean below about 2000 m. Zonal wind stress changes such as these may be expected to enhance the mesoscale eddy activity in the Southern Ocean.
Quantitative integration of seismic and GPR reflections to derive unique estimates for water saturation and porosity in subsoil
Authors: Ghose R. , Slob E. C.
Published: March 2006

For shallow subsoil, the estimates of in‐situ porosity and water saturation are important, but until now it has been difficult to estimate them reliably. We relate seismic and GPR reflection coefficients to porosity and water saturation using a shared earth model. Using this model, we propose a method to integrate quantitatively seismic and GPR angle‐dependent reflection coefficients. The new approach has been tested through numerical simulations. The results clearly show that from either seismic or GPR data alone it is impossible to obtain unique estimates for porosity and water saturation; however, a correct integration of those two data types leads to unique and stable estimates at a subsoil layer boundary. Potential applications of this approach exist in hydrogeology and environmental, agricultural and geotechnical engineering.
Influence of continental roots and asthenosphere on plate‐mantle coupling
Authors: Conrad Clinton P. , Lithgow‐Bertelloni Carolina
Published: March 2006

The shear tractions that mantle flow exerts on the base of Earth's lithosphere contribute to plate‐driving forces and lithospheric stresses. We investigate the sensitivity of these tractions to sub‐lithospheric viscosity variations by comparing shear tractions computed from a mantle flow model featuring laterally‐varying lithosphere and asthenosphere viscosity with those from a model with layered viscosity. Lateral viscosity variations generally do not change the direction of shear tractions, but deeply penetrating continental roots increase traction magnitudes by a factor of 2–5 compared to 100 km thick lithosphere. A low‐viscosity asthenosphere decreases traction magnitudes by a smaller amount, and is important only if >100 km thick. Increased plate‐mantle coupling beneath thick continental lithosphere may increase plate‐driving forces, surface deformation, and mantle‐derived lithospheric stresses in these regions. By contrast, a low‐viscosity asthenosphere does not decouple the lithosphere from mantle flow, highlighting the geological importance of mantle tractions on the lithosphere.
Variation of solar cyclicity during the Spoerer Minimum
Authors: Miyahara Hiroko , Masuda Kimiaki , Muraki Yasushi , Kitagawa Hiroyuki , Nakamura Toshio
Published: March 2006

We investigate the 11‐year solar cycle during the Spoerer Minimum (1415–1534 A.D.) by measuring the carbon 14 content in the annual tree rings for the period 1413–1554 A.D. The period of the Spoerer Minimum is assumed to be a prolonged sunspot minimum like the Maunder Minimum (1645–1715 A.D.). However, the 11‐year solar cycle, which appears in recent solar variations, was also prominently detected in the carbon 14 record during this period. The amplitude of the 11‐year cycle seems to have been modulated only around 1455–1510 A.D.
Atmospheric Radiation Measurement site atmospheric state best estimates for Atmospheric Infrared Sounder temperature and water vapor retrieval validation
Authors: Tobin David C. , Revercomb Henry E. , Knuteson Robert O. , Lesht Barry M. , Strow L. Larrabee , Hannon Scott E. , Feltz Wayne F. , Moy Leslie A. , Fetzer Eric J. , Cress Ted S.
Published: March 2006

The Atmospheric Infrared Sounder (AIRS) is the first of a new generation of advanced satellite‐based atmospheric sounders with the capability of obtaining high–vertical resolution profiles of temperature and water vapor. The high‐accuracy retrieval goals of AIRS (e.g., 1 K RMS in 1 km layers below 100 mbar for air temperature, 10% RMS in 2 km layers below 100 mbar for water vapor concentration), combined with the large temporal and spatial variability of the atmosphere and difficulties in making accurate measurements of the atmospheric state, necessitate careful and detailed validation using well‐characterized ground‐based sites. As part of ongoing AIRS Science Team efforts and a collaborative effort between the NASA Earth Observing System (EOS) project and the Department of Energy Atmospheric Radiation Measurement (ARM) program, data from various ARM and other observations are used to create best estimates of the atmospheric state at the Aqua overpass times. The resulting validation data set is an ensemble of temperature and water vapor profiles created from radiosondes launched at the approximate Aqua overpass times, interpolated to the exact overpass time using time continuous ground‐based profiles, adjusted to account for spatial gradients within the Advanced Microwave Sounding Unit (AMSU) footprints, and supplemented with limited cloud observations. Estimates of the spectral surface infrared emissivity and local skin temperatures are also constructed. Relying on the developed ARM infrastructure and previous and ongoing characterization studies of the ARM measurements, the data set provides a good combination of statistics and accuracy which is essential for assessment of the advanced sounder products. Combined with the collocated AIRS observations, the products are being used to study observed minus calculated AIRS spectra, aimed at evaluation of the AIRS forward radiative transfer model, AIRS observed radiances, and temperature and water vapor profile retrievals. This paper provides an introduction to the ARM site best estimate validation products and characterizes the accuracy of the AIRS team version 4 atmospheric temperature and water vapor retrievals using the ARM products. The AIRS retrievals over tropical ocean are found to have very good accuracy for both temperature and water vapor, with RMS errors approaching the theoretical expectation for clear sky conditions, while retrievals over a midlatitude land site have poorer performance. The results demonstrate the importance of using specialized “truth” sites for accurate assessment of the advanced sounder performance and motivate the continued refinement of the AIRS science team retrieval algorithm, particularly for retrievals over land.
Global evaluation of CCN formation by direct emission of sea salt and growth of ultrafine sea salt
Authors: Pierce Jeffrey R. , Adams Peter J.
Published: March 2006

The contribution of both the sea‐salt emissions and specifically the ultrafine (dry Dp < 0.1 μm) component of these emissions to global CCN was assessed with a global model of aerosol microphysics. Four sea‐salt emissions parameterizations were incorporated into the GISS II‐prime general circulation model with the size‐resolved aerosol microphysics module, TOMAS. The results of the four simulations were compared to observations of monthly average PM10 sea‐salt mass, sea‐salt mass size distributions, and marine aerosol number distributions. The agreement of the simulations with the observations varied greatly based on the sea‐salt emissions parameterization used, but validation of the parameterizations is limited by uncertainty in the model's wind speeds. The impact of sea‐salt aerosols on CCN concentrations was assessed by looking at the percent change in CCN(0.2%) concentrations between a simulation including both sea salt and sulfate and a simulation including sulfate alone. Two of the emissions parameterizations included ultrafine sea‐salt particles, and the contribution of the ultrafine particles to CCN(0.2%) formation was assessed by sensitivity studies. Depending on the emissions estimate used, the addition of sea salt increased CCN(0.2%) over the Southern Ocean by 150% to 500%. The highest increases resulted from the simulations that included ultrafine emissions where it was found that the ultrafine sea salt can increase CCN(0.2%) concentrations over both the Southern Ocean and Antarctica by more than 50% relative to the same parameterizations with ultrafine sea salt excluded. The sensitivity of CCN(0.2%) to ultrafine sea‐salt emissions enhances the importance of reducing the uncertainty of sea‐salt emissions parameterizations and their subsequent treatment in aerosol models.
Effects of aqueous organosulfur chemistry on particulate methanesulfonate to non–sea salt sulfate ratios in the marine atmosphere
Authors: Zhu Lei , Nenes Athanasios , Wine Paul H. , Nicovich J. Michael
Published: March 2006

The oxidation of dimethyl sulfide (DMS, CH3SCH3) in the atmosphere could influence climate by affecting cloud condensation nuclei concentrations and cloud properties. This work focuses on elucidating the importance of DMS‐cloud interactions, especially the poorly understood aqueous phase chemical transformations of DMS oxidation products. For this purpose, we incorporate an oxidation mechanism of atmospheric DMS and its products within the modeling framework of a trajectory ensemble model (TEM). Both marine cumulus and stratocumulus clouds are considered. It is found that the aqueous phase reactions of sulfur compounds contribute >97% of methanesulfonate (MS, CH3(O)S(O)O−) and >80% of non–sea salt sulfate (NSS) production in particles and that about 30% of total MS and NSS production is from the aqueous phase oxidation of the organosulfur compounds. The aqueous phase methanesulfinate (MSI, CH3S(O)O−) + Cl2− reaction is found to be more important than MSI + OH as an MS source. The MS + OH reaction could consume almost 20% of MS and produce about 8% of total NSS within 3 days under typical marine atmospheric conditions.
Evaluation of surface water fluxes of the pan‐Arctic land region with a land surface model and ERA‐40 reanalysis
Authors: Su Fengge , Adam Jennifer C. , Trenberth Kevin E. , Lettenmaier Dennis P.
Published: March 2006

The seasonal, spatial, and latitudinal variability of precipitation (P), evapotranspiration (E), and runoff (R) are examined for large Arctic river basins and for the entire pan‐Arctic domain using a 21‐year off‐line simulation of the Variable Infiltration Capacity (VIC) macroscale hydrology model and the ERA‐40 reanalysis. Observed P used in the VIC model (corrected for gauge catch deficiency) is compared with that from the ERA‐40 reanalysis. Gridded values of evapotranspiration minus precipitation (E‐P) are calculated from the ERA‐40 atmospheric water budget, and estimates of implied E are obtained as the residual of observed P and ERA‐40 E‐P. The ERA‐40 P is surprisingly close to observations on an annual basis over the large river basins (especially accounting for known errors in the observations). Furthermore, ERA‐40 P is quite consistent with observations in terms of interannual, spatial, and latitudinal variations. ERA‐40 E is generally higher than both VIC E and implied E in spring and autumn. However, VIC estimates more E in June and July than either ERA‐40 or the atmospheric budget for the Yenisei, Ob, and Mackenzie River basins. The ERA‐40 bias toward early snowmelt and a double runoff peak (not present in VIC or observations) indicates the need for improvements in the ECMWF land surface scheme. The long‐term means of ERA‐40 vapor convergence P‐E for the Lena, Yenisei, Ob, and Mackenzie are not in balance with observed runoff, mainly due to the uncertainties in computed P‐E and observed streamflow.
Antarctic mesospheric temperature estimation using the Davis mesosphere‐stratosphere‐troposphere radar
Authors: Holdsworth David A. , Morris Ray J. , Murphy Damian J. , Reid Iain M. , Burns Gary B. , French W. John R.
Published: March 2006

This paper presents the first Antarctic meteor radar temperature estimates. These temperatures have been derived from meteor diffusion coefficients using two techniques: pressure model and temperature gradient model. The temperatures are compared with a temperature model derived using colocated OH spectrometer measurements and Northern Hemisphere rocket observations. Pressure model temperatures derived using rocket‐derived pressures show good agreement with the temperature model, while those derived using Mass Spectrometer and Incoherent Scatter (MSIS) and CIRA model pressures show good agreement in winter but poor agreement in summer. This confirms previous studies suggesting the unreliability of high‐latitude CIRA pressures. The temperature gradient model temperatures show good agreement with the temperature model but show larger fluctuations than the pressure model temperatures. Meteor temperature estimates made during the Southern delta‐Aquarids meteor shower are shown to be biased, suggesting that care should be taken in applying meteor temperature estimation during meteor showers. On the basis of our results we recommend the use of the pressure model technique at all sites, subject to determination of an appropriate pressure model.
Extensive phytoplankton blooms in the Atlantic sector of the glacial Southern Ocean
Authors: Abelmann Andrea , Gersonde Rainer , Cortese Giuseppe , Kuhn Gerhard , Smetacek Victor
Published: March 2006

The sources and sinks of atmospheric carbon dioxide over glacial/interglacial cycles are under debate. Variation in productivity of the Antarctic Circumpolar Current (ACC) could potentially play a significant role, but current interpretations of sedimentary geochemical proxies suggest that glacial productivity was not higher than today. We present areal and down‐core distribution patterns of previously overlooked diatom resting spores that indicate the occurrence of extensive phytoplankton blooms across the entire Atlantic sector of the ACC, particularly in the seasonal ice zone (SIZ), linked to higher iron input during the last glacial. Sea ice acts as an effective transporter of iron and enhances its bioavailability. The dominance of the deep living radiolarian Cyladophora davisiana in glacial SIZ sediments indicates that organic carbon export to mesopelagic depths was at least tenfold higher than today.
EAAC1 Glutamate Transporter Expression in the Rat Lithium-Pilocarpine Model of Temporal Lobe Epilepsy
Authors: Voutsinos-Porche Brigitte , Koning Estelle , Cléent Yann , Kaplan Hervé , Ferrandon Arielle , Motte Jacques , Nehlig Astrid
Published: March 2006

Glutamate excitotoxicity has been involved in the pathophysiology of epilepsy. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. Using densitometric immunohistochemical analysis, we examined the temporal expression of the neuronal glutamate transporter (EAAC1) in the lithium-pilocarpine rat model of temporal lobe epilepsy. During the acute period of lithium-pilocarpine-induced status epilepticus, EAAC1 transporter expression increased in the pyramidal neurons of cornus ammonis (CA)1, CA2 and CA3 (fields of the hippocampus), in dentate gyrus (DG) granule cells and in olfactory tubercle (Tu). During the latent period, EAAC1 expression was strongly expressed in the DG granular and molecular layers, Tu, cerebral cortex and septum, and went back to control levels in CA1, CA2 and CA3 layers. The overexpression of EAAC1 occurred mainly in structures prone to develop Fluoro-Jade-B-positive degenerating neurons. It is, however, not clear to what extent the overexpression of EAAC1 contributes to epileptogenesis and in which area it may represent a preventive or compensatory or response to injury.
Epidermal growth factor-regulated activation of Rac GTPase enhances CD44 cleavage by metalloproteinase disintegrin ADAM10
Authors: Murai Toshiyuki , Miyauchi Takayuki , Yanagida Toshio , Sako Yasushi
Published: March 2006

Invasive tumour cells, such as gliomas, frequently express EGF (epidermal growth factor) receptor at a high level and they exhibit enhanced cell migration in response to EGF. We reported previously that tumour cell migration is associated with ectodomain cleavage of CD44, the major adhesion molecule that is implicated in tumour invasion and metastasis, and that the cleavage is enhanced by ligation of CD44. In the present study, we show that EGF promotes CD44 cleavage and CD44-dependent cell migration. Introduction of a dominant-negative mutant of the small GTPase Rac1 or depletion of Rac1 by RNAi (RNA interference) abrogated CD44 cleavage induced by EGF. Treatment with PD98059, an inhibitor for MEK (mitogen-activated protein kinase/extracellular-signal-regulated kinase kinase), also suppressed the CD44 cleavage. Furthermore, RNAi studies showed that EGF induced ADAM10 (a disintegrin and metalloproteinase 10)-dependent CD44 cleavage and cell migration. These results indicate that EGF induces ADAM10-mediated CD44 cleavage through Rac1 and mitogen-activated protein kinase activation, and thereby promotes tumour cell migration and invasion.
Peroxisome-proliferator-activated receptor α agonists inhibit cyclo-oxygenase 2 and vascular endothelial growth factor transcriptional activation in human colorectal carcinoma cells via inhibition of activator protein-1
Authors: Grau Raquel , Punzón Carmen , Fresno Manuel , Iñiguez Miguel A.
Published: March 2006

Recent evidence indicates that PPAR (peroxisome-proliferator-activated receptor) α ligands possess anti-inflammatory and antitumoural properties owing to their inhibitory effects on the expression of genes that are involved in the inflammatory response. However, the precise molecular mechanisms underlying these effects are poorly understood. In the present study, we show that tumour promoter PMA-mediated induction of genes that are significantly associated with inflammation, tumour growth and metastasis, such as COX-2 (cyclo-oxygenase 2) and VEGF (vascular endothelial growth factor), is inhibited by PPARα ligands in the human colorectal carcinoma cell line SW620. PPARα activators LY-171883 and WY-14,643 were able to diminish transcriptional induction of COX-2 and VEGF by inhibiting AP-1 (activator protein-1)-mediated transcriptional activation induced by PMA or by c-Jun overexpression. The actions of these ligands on AP-1 activation and COX-2 and VEGF transcriptional induction were found to be dependent on PPARα expression. Our studies demonstrate the existence of a negative cross-talk between the PPARα- and AP-1-dependent signalling pathways in these cells. PPARα interfered with at least two steps within the pathway leading to AP-1 activation. First, PPARα activation impaired AP-1 binding to a consensus DNA sequence. Secondly, PPARα ligands inhibited c-Jun transactivating activity. Taken together, these findings provide new insight into the anti-inflammatory and anti-tumoural properties of PPARα activation, through the inhibition of the induction of AP-1-dependent genes that are involved in inflammation and tumour progression.
Involvement of the Gi/o/cGMP/PKG pathway in the AT2-mediated inhibition of outer cortex proximal tubule Na+-ATPase by Ang-(1–7)
Authors: Lara Lucienne da Silva , Cavalcante Fabíola , Axelband Flavia , De Souza Aloa Machado , Lopes Anibal Gil , Caruso-Neves Celso
Published: March 2006

The molecular mechanisms involved in the Ang-(1–7) [angiotensin-(1–7)] effect on sodium renal excretion remain to be determined. In a previous study, we showed that Ang-(1–7) has a biphasic effect on the proximal tubule Na+-ATPase activity, with the stimulatory effect mediated by the AT1 receptor. In the present study, we investigated the molecular mechanisms involved in the inhibition of the Na+-ATPase by Ang-(1–7). All experiments were carried out in the presence of 0.1 nM losartan to block the AT1 receptor-mediated stimulation. In this condition, Ang-(1–7) at 0.1 nM inhibited the Na+-ATPase activity of the proximal tubule by 54%. This effect was reversed by 10 nM PD123319, a specific antagonist of the AT2 receptor, and by 1 μM GDP[β-S] (guanosine 5′-[β-thio]diphosphate), an inhibitor of G protein. Ang-(1–7) at 0.1 M induced [35S]GTP[S] (guanosine 5′-[γ-[35S]thio]triphosphate) binding and 1 μg/ml pertussis toxin, an inhibitor of Gi/o protein, reversed the Ang-(1–7) effect. Furthermore, it was observed that the inhibitory effect of Ang-(1–7) on the Na+-ATPase activity was completely reversed by 0.1 μM LY83583, an inhibitor of guanylate cyclase, and by 2 μM KT5823, a PKG (protein kinase G) inhibitor, and was mimicked by 10 nM d-cGMP (dibutyryl cGMP). Ang-(1–7) increased the PKG activity by 152% and this effect was abolished by 10 nM PD123319 and 0.1 μM LY83583. Taken together, these data indicate that Ang-(1–7) inhibits the proximal tubule Na+-ATPase by interaction with the AT2 receptor that subsequently activates the Gi/o protein/cGMP/PKG pathway.
Gene expression profiling of mice with genetically modified muscle glycogen content
Authors: Parker Gretchen E. , Pederson Bartholomew A. , Obayashi Mariko , Schroeder Jill M. , Harris Robert A. , Roach Peter J.
Published: March 2006

Glycogen, a branched polymer of glucose, forms an energy re-serve in numerous organisms. In mammals, the two largest glyco-gen stores are in skeletal muscle and liver, which express tissue-specific glycogen synthase isoforms. MGSKO mice, in which mGys1 (mouse glycogen synthase) is disrupted, are devoid of muscle glycogen [Pederson, Chen, Schroeder, Shou, DePaoli-Roach and Roach (2004) Mol. Cell. Biol. 24, 7179–7187]. The GSL30 mouse line hyper-accumulates glycogen in muscle [Manchester, Skurat, Roach, Hauschka and Lawrence (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 10707–10711]. We performed a microarray analysis of mRNA from the anterior tibialis, medial gastrocnemius and liver of MGSKO mice, and from the gastroc-nemius of GSL30 mice. In MGSKO mice, transcripts of 79 genes varied in their expression in the same direction in both the anterior tibialis and gastrocnemius. These included several genes encoding proteins proximally involved in glycogen metabolism. The Ppp1r1a [protein phosphatase 1 regulatory (inhibitor) sub-unit 1A] gene underwent the greatest amount of downregulation. In muscle, the downregulation of Pfkfb1 and Pfkfb3, encoding isoforms of 6-phosphofructo-2-kinase/fructose-2,6-bisphospha-tase, is consistent with decreased glycolysis. Pathways for branched-chain amino acid, and ketone body utilization appear to be downregulated, as is the capacity to form the gluconeogenic precursors alanine, lactate and glutamine. Expression changes among several members of the Wnt signalling pathway were identified, suggesting an as yet unexplained role in glycogen meta-bolism. In liver, the upregulation of Pfkfb1 and Pfkfb3 expression is consistent with increased glycolysis, perhaps as an adaptation to altered muscle metabolism. By comparing changes in muscle expression between MGSKO and GSL30 mice, we found a subset of 44 genes, the expression of which varied as a function of muscle glycogen content. These genes are candidates for regulation by glycogen levels. Particularly interesting is the observation that 11 of these genes encode cardiac or slow-twitch isoforms of muscle contractile proteins, and are upregulated in muscle that has a greater oxidative capacity in MGSKO mice.
Activation of classical protein kinase C reduces the expression of human cationic amino acid transporter 3 (hCAT-3) in the plasma membrane
Authors: Rotmann Alexander , Vékony Nicole , Gassner Davina , Niegisch Günter , Strand Dennis , Martiné Ursula , Closs Ellen I.
Published: March 2006

We have previously shown that activation of PKC (protein kinase C) results in internalization of hCAT-1 [human CAT-1 (cationic amino acid transporter 1)] and a decrease in arginine transport [Rotmann, Strand, Martiné and Closs (2004) J. Biol. Chem. 279, 54185–54192]. However, others found increased transport rates for arginine in response to PKC activation, suggesting a differential effect of PKC on different CAT isoforms. Therefore we investigated the effect of PKC on hCAT-3, an isoform expressed in thymus, brain, ovary, uterus and mammary gland. In Xenopus laevis oocytes and human U373MG glioblastoma cells, hCAT-3-mediated L-arginine transport was significantly reduced upon treatment with compounds that activate classical PKC. In contrast, inactive phorbol esters and an activator of novel PKC isoforms had no effect. PKC inhibitors (including the PKCα-preferring Ro 31-8280) reduced the inhibitory effect of the PKC-activating compounds. Microscopic analyses revealed a PMA-induced reduction in the cell-surface expression of fusion proteins between hCAT-3 and enhanced green fluorescent protein expressed in X. laevis oocytes and glioblastoma cells. Western-blot analysis of biotinylated surface proteins demonstrated a PMA-induced decrease in hCAT-3 in the plasma membrane, but not in total protein lysates. Pretreatment with a PKC inhibitor also reduced this PMA effect. It is concluded that similar to hCAT-1, hCAT-3 activity is decreased by PKC via reduction of transporter molecules in the plasma membrane. Classical PKC isoforms seem to be responsible for this effect.
Amplification and disruption of the phenylacetyl-CoA ligase gene of Penicillium chrysogenum encoding an aryl-capping enzyme that supplies phenylacetic acid to the isopenicillin N-acyltransferase
Authors: Lamas-Maceiras Mónica , Vaca Inmaculada , Rodríguez Esther , Casqueiro Javier , Martín Juan F.
Published: March 2006

A gene, phl, encoding a phenylacetyl-CoA ligase was cloned from a phage library of Penicillium chrysogenum AS-P-78. The presence of five introns in the phl gene was confirmed by reverse transcriptase-PCR. The phl gene encoded an aryl-CoA ligase closely related to Arabidopsis thaliana 4-coumaroyl-CoA ligase. The Phl protein contained most of the amino acids defining the aryl-CoA (4-coumaroyl-CoA) ligase substrate-specificity code and differed from acetyl-CoA ligase and other acyl-CoA ligases. The phl gene was not linked to the penicillin gene cluster. Amplification of phl in an autonomous replicating plasmid led to an 8-fold increase in phenylacetyl-CoA ligase activity and a 35% increase in penicillin production. Transformants containing the amplified phl gene were resistant to high concentrations of phenylacetic acid (more than 2.5 g/l). Disruption of the phl gene resulted in a 40% decrease in penicillin production and a similar reduction of phenylacetyl-CoA ligase activity. The disrupted mutants were highly susceptible to phenylacetic acid. Complementation of the disrupted mutants with the phl gene restored normal levels of penicillin production and resistance to phenylacetic acid. The phenylacetyl-CoA ligase encoded by the phl gene is therefore involved in penicillin production, although a second aryl-CoA ligase appears to contribute partially to phenylacetic acid activation. The Phl protein lacks a peptide-carrier-protein domain and behaves as an aryl-capping enzyme that activates phenylacetic acid and transfers it to the isopenicillin N acyltransferase. The Phl protein contains the peroxisome-targeting sequence that is also present in the isopenicillin N acyltransferase. The peroxisomal co-localization of these two proteins indicates that the last two enzymes of the penicillin pathway form a peroxisomal functional complex.
Stable peptide inhibitors prevent binding of lethal and oedema factors to protective antigen and neutralize anthrax toxin in vivo
Authors: Pini Alessandro , Runci Ylenia , Falciani Chiara , Lelli Barbara , Brunetti Jlenia , Pileri Silvia , Fabbrini Monica , Lozzi Luisa , Ricci Claudia , Bernini Andrea , Tonello Fiorella , Dal Molin Federica , Neri Paolo , Niccolai Neri , Bracci Luisa
Published: March 2006

The lethal and oedema toxins produced by Bacillus anthracis, the aetiological agent of anthrax, are made by association of protective antigen with lethal and oedema factors and play a major role in the pathogenesis of anthrax. In the present paper, we describe the production of peptide-based specific inhibitors in branched form which inhibit the interaction of protective antigen with lethal and oedema factors and neutralize anthrax toxins in vitro and in vivo. Anti-protective antigen peptides were selected from a phage library by competitive panning with lethal factor. Selected 12-mer peptides were synthesized in tetra-branched form and were systematically modified to obtain peptides with higher affinity and inhibitory efficiency.
Weak acid and alkali stress regulate phosphatidylinositol bisphosphate synthesis in Saccharomyces cerevisiae
Authors: Mollapour Mehdi , Phelan John P. , Millson Stefan H. , Piper Peter W. , Cooke Frank T.
Published: March 2006

Weak organic acids are used as food preservatives to inhibit the growth of spoilage yeasts, including Saccharomyces cerevisiae. Long-term adaptation to weak acids requires the increased expression of the ATP-binding cassette transporter Pdr12p, which catalyses the active efflux of the weak acids from the cytosol; however, very little is known about the signalling events immediately following application of weak acid stress. We have investigated the effects of weak acids on two stress-responsive signalling molecules, PtdIns(3,5)P2 and PtdIns(4,5)P2, which in S. cerevisiae are synthesized by Fab1p and Mss4p respectively. At low extracellular pH, benzoic acid, sorbic acid and acetic acid all cause a transient reduction in PtdIns(3,5)P2 accumulation and a more persistent rise in PtdIns(4,5)P2 levels. The increase in PtdIns(4,5)P2 levels is accompanied by a reorganization of the actin cytoskeleton. However, changes in PtdInsP2 levels are independent of weak acid-induced Pdr12p expression. In contrast, changing the extracellular medium to alkaline pH provokes a prolonged and substantial rise in PtdIns(3,5)P2 levels. As PtdIns(3,5)P2 synthesis is required for correct vacuole acidification, it is possible that levels of this molecule are modulated to maintain intracellular pH homoeostasis in response to weak acid and alkali stresses. In conclusion, we have expanded the repertoire of stress responses that affect PtdInsP2 levels to include weak acid and alkali stresses.
Structural insight into the ligand specificity of a thermostable family 51 arabinofuranosidase, Araf51, from Clostridium thermocellum
Authors: Taylor Edward J. , Smith Nicola L. , Turkenburg Johan P. , D'Souza Simone , Gilbert Harry J. , Davies Gideon J.
Published: March 2006

The digestion of the plant cell wall requires the concerted action of a diverse repertoire of enzyme activities. An important component of these hydrolase consortia are arabinofuranosidases, which release L-arabinofuranose moieties from a range of plant structural polysaccharides. The anaerobic bacterium Clostridium thermocellum, a highly efficient plant cell wall degrader, possesses a single α-L-arabinofuranosidase (EC 3.2.1.55), CtAraf51A, located in GH51 (glycoside hydrolase family 51). The crystal structure of the enzyme has been solved in native form and in ‘Michaelis’ complexes with both α-1,5-linked arabinotriose and α-1,3 arabinoxylobiose, both forming a hexamer in the asymmetric unit. Kinetic studies reveal that CtAraf51A, in contrast with well-characterized GH51 enzymes including the Cellvibrio japonicus enzyme [Beylot, McKie, Voragen, Doeswijk-Voragen and Gilbert (2001) Biochem. J. 358, 607–614], catalyses the hydrolysis of α-1,5-linked arabino-oligosaccharides and the α-1,3 arabinosyl side chain decorations of xylan with equal efficiency. The paucity of direct hydrogen bonds with the aglycone moiety and the flexible conformation adopted by Trp178, which stacks against the sugar at the +1 subsite, provide a structural explanation for the plasticity in substrate specificity displayed by the clostridial arabinofuranosidase.
Peptide inhibitors MAP the way towards fighting anthrax pathogenesis
Authors: deCathelineau Aimee M. , Bokoch Gary M.
Published: March 2006

The pathogenesis of anthrax is such that unless antibiotic treatment is initiated at an early stage in the disease, it is ineffective against the bacteria-induced toxaemia that subverts the immune response, inflicts massive tissue damage and is ultimately the major factor contributing to death during anthrax infection. As current events have demonstrated the feasibility of the use of anthrax as a bioterrorism agent, and exemplified the difficulty of treating the ensuing infection, inhibition of anthrax toxin has become a major focus of research for the design of antitoxin therapeutics. In this issue of Biochemical Journal, Bracci and co-workers describe the discovery by competitive screening of a phage-display library of a peptide inhibitor of anthrax toxin assembly that shows great promise towards the treatment of anthrax.
Antisense therapy in malignant diseases: status quo and quo vadis?
Authors: Tamm Ingo
Published: March 2006

Preclinical and clinical studies indicate a role for AS ODNs (antisense oligonucleotides) as therapeutics for malignant diseases. The principle of antisense technology is the sequence-specific binding of an AS ODN to the target mRNA, resulting in a translational arrest. The specificity of hybridization makes antisense strategy attractive to selectively modulate the expression of genes involved in the pathogenesis of malignant diseases. One antisense drug has been approved for local therapy of CMV (cytomegalovirus) retinitis, and a number of AS ODNs are currently being tested in clinical trials, including AS ODN targeting Bcl-2, XIAP (X-linked inhibitor of apoptosis protein) and TGF-β-2 (transforming growth factor β-2). AS ODNs are well tolerated and may have therapeutic activity. In particular, an AS ODN to Bcl-2 has been tested in phase III clinical trials in chronic lymphocytic leukaemia, multiple myeloma and malignant melanoma. In this review, therapeutic concepts, clinical studies and new promising molecular targets to treat malignancies with AS ODNs are summarized.
Increased systemic inflammation and oxidative stress in patients with worsening congestive heart failure: improvement after short-term inotropic support
Authors: White Michel , Ducharme Anique , Ibrahim Reda , Whittom Lucette , Lavoie Joel , Guertin Marie-Claude , Racine Normand , He Ying , Yao Guoying , Rouleau Jean L. , Schiffrin Ernesto L. , Touyz Rhian M.
Published: March 2006

In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidative stress in patients with decompensated CHF (congestive heart failure) and assessed whether clinical recompensation by short-term inotropic therapy influences these parameters. Patients with worsening CHF (n=29, aged 61.9±2.7 years), NYHA (New York Heart Association) class III–IV, and left ventricular ejection fraction of 23.7±1.8% were studied. Controls comprised age-matched healthy volunteers (n=15; 54.1±3.2 years). Plasma levels of cytokines [IL (interleukin)-6 and IL-18], chemokines [MCP-1 (monocyte chemotactic protein-1)], adhesion molecules [sICAM (soluble intercellular adhesion molecule), sE-selectin (soluble E-selectin)], systemic markers of oxidation [TBARS (thiobarbituric acid-reactive substances), 8-isoprostaglandin F2α and nitrotyrosine] and hs-CRP (high-sensitivity C-reactive protein) were measured by ELISA and colorimetric assays at admission and 30 days following 72-h milrinone (n=15) or dobutamine (n=14) infusion. Plasma IL-6, IL-18, sICAM, E-selectin, hs-CRP and oxidative markers were significantly higher in patients on admission before inotropic treatment compared with controls (P<0.05). Short-term inotropic support improved clinical status as assessed by NYHA classification and by the 6-min walk test and significantly decreased plasma levels of IL-6, IL-18, sICAM, hs-CRP and markers of oxidation (P<0.05) at 30 days. The effects of milrinone and dobutamine were similar. In conclusion, our results demonstrate that patients with decompensated CHF have marked systemic inflammation and increased production of oxygen free radicals. Short-term inotropic support improves functional status and reduces indices of inflammation and oxidative stress in patients with decompensated CHF.
Searching for genetic clues to the causes of pre-eclampsia
Authors: Chappell Sally , Morgan Linda
Published: March 2006

Pre-eclampsia and its related syndromes are significant causes of maternal and fetal death, but much remains unclear about the underlying disease mechanisms. Epidemiological research has consistently demonstrated a familial predisposition to pre-eclampsia, which has encouraged genetic research in this area. The goal is the discovery of susceptibility genes which will inform understanding of the pathophysiology of pre-eclampsia, and may prove to be targets for therapeutic or preventative strategies. This review examines the application of molecular technologies to the search for genetic clues in pre-eclampsia and emphasizes the importance of integrative approaches. The results of recent genome-wide linkage studies have been particularly encouraging, identifying a number of loci which merit closer examination. Candidate gene studies have proved less fruitful, generating conflicting and inconclusive results. Possible explanations and remedies for this deficiency are discussed with a view to stimulating closer collaboration between researchers in this field.
Ballonkyphoplastie: Indikation, Diagnostik, operative Technik, Ergebnisse. Teil 1
Authors: Glasmacher S. , Blattert T. R. , Siekmann H. , Josten C.
Published: March 2006

Bei der Ballonkyphoplastie handelt es sich um ein relativ neues minimalinvasives Verfahren zur Stabilisierung und Schmerzreduktion bei osteoporotischen Frakturen. Hierbei werden trans- oder extrapedikulär Hohlnadeln vorgeschoben. Durch die Auffüllung der hierüber vorgeführten Ballone erfolgt eine Aufrichtung des frakturierten Wirbelkörpers mit Schaffung von präformierten Kavernen. Diese werden nach Entfernung der Ballone mit hochviskösem Zement gefüllt. Hauptindikation sind die osteoporotischen Frakturen. In Abhängigkeit von Frakturalter und ‐typ kann eine vollständige Reposition erreicht werden. Obwohl auf die A-Frakturen beschränkt, zeigen aktuelle Ballonentwicklungen neue Wege mit möglicherweise breiterem Indikationsspektrum. Im Vergleich zur Vertebroplastie zeigt sich eine deutlich geringere Komplikationsrate bei ebenfalls konsequenter Schmerzreduktion.
Coalescence of magnetic islands, sloshing, and the pressure problem
Authors: Knoll D. A. , Chacón L.
Published: March 2006

The coalescence of magnetic islands in the high Lundquist number regime is studied. Within the resistive magnetohydrodynamics model, the coalescence rate is known to stall (sloshing) in the limit of high Lundquist number. Previously, this stalling has been associated with the presence of a secondary tearing mode. Here it is shown that this stalling results from high magnetic pressure gradients, which result from thin current sheets at high Lundquist number. This phenomenon is frequently referred to as the “pressure problem” in flux pile-up reconnection studies. Sensitivity of the dynamic solution is presented, over a wide range of resistivities.
Simple dissipative quartz crystal microbalance and methods for determining dissipation decay constants
Authors: Wu Kun , Wu Bing , Feng C.-Q. , Du Xianbin , Huang Huan , Yin Zejie , Zhu Da-Ming
Published: March 2006

We describe a simple dissipative quartz crystal microbalance (QCM) and two simple methods for determining the dissipation factor. The microbalance consists of an oscillator circuit interfaced with a personal computer. The oscillation voltages are undersampled through a low speed data acquisition card. Both methods for determining the resonant frequency and the dissipation factor assume a limited variation of the resonant frequency, which is the case for general applications of QCMs. The first method directly fits the undersampled data with a nonlinear function. The second method determines the resonant frequency of a quartz crystal by Fourier transformation of the acquired data. The dissipation factor is obtained by rectifying the undersampled data and then fitting them with an exponential function.
The correlation consistent composite approach (ccCA): An alternative to the Gaussian-n methods
Authors: DeYonker Nathan J. , Cundari Thomas R. , Wilson Angela K.
Published: March 2006

An alternative to the Gaussian-n (G1, G2, and G3) composite methods of computing molecular energies is proposed and is named the “correlation consistent composite approach” (ccCA, ccCA-CBS-1, ccCA-CBS-2). This approach uses the correlation consistent polarized valence (cc-pVXZ) basis sets. The G2-1 test set of 48 enthalpies of formation (ΔHf), 38 adiabatic ionization potentials (IPs), 25 adiabatic electron affinities (EAs), and 8 adiabatic proton affinities (PAs) are computed using this approach, as well as the ΔHf values of 30 more systems. Equilibrium molecular geometries and vibrational frequencies are obtained using B3LYP density functional theory. When applying the ccCA-CBS method with the cc-pVXZ series of basis sets augmented with diffuse functions, mean absolute deviations within the G2-1 test set compared to experiment are 1.33kcalmol−1 for ΔHf,0.81kcalmol−1 for IPs, 1.02kcalmol−1 for EAs, and 1.51kcalmol−1 for PAs, without including the “high-level correction” (HLC) contained in the original Gn methods. Whereas the HLC originated in the Gaussian-1 method as an isogyric correction, it evolved into a fitted parameter that minimized the error of the composite methods, eliminating its physical meaning. Recomputing the G1 and G3 enthalpies of formation without the HLC reveals a systematic trend where most ΔHf values are significantly higher than experimental values. By extrapolating electronic energies to the complete basis set (CBS) limit and adding G3-like corrections for the core-valence and infinite-order electron correlation effects, ccCA-CBS-2 often underestimates the experimental ΔHf, especially for larger systems. This is desired as inclusion of relativistic and atomic spin-orbit effects subsequently improves theoretical ΔHf values to give a 0.81kcalmol−1 mean absolute deviation with ccCA-CBS-2. The ccCA-CBS method is a viable “black box” method that can be used on systems with at least 10–15 heavy atoms.
Theory of boundary-free two-dimensional dust clusters
Authors: Tsytovich V. N. , Gousein-zade N. G. , Morfill G. E.
Published: March 2006

It is shown theoretically that a stable two-dimensional (2D) grain cluster can exist in plasmas without external confinement if the shadow attraction of grains is taken into account. These are considered as boundary-free clusters. The equilibrium radius of the clusters is investigated numerically. It is found that it is rapidly decreasing with an increase of the attraction coefficient and with an increase of the number of grains N in the cluster. Comparison of energies of one shell cluster containing N grains with the energies of a cluster with N−1 grains in the shell and an additional one grain in the center as functions of the attraction coefficient is used to find the magic numbers for new shell creation. It is demonstrated that a dissociation of the cluster in several smaller clusters requires less energy than a removal of one of the grains from the cluster. The computations were performed for the Debye screening and for the nonlinear screening models and show that the structure of the clusters is sensitive to the type of screening. Frequencies of all collective modes of the 2D boundary-free clusters are calculated up to N=7 grains in the cluster for the case where all grains form one shell cluster and for the case where N=6 grains form one shell cluster and one of the grains is located at the center of the cluster. The frequencies of the modes increase with a decrease of the cluster radius. Stable and unstable modes are investigated as a function of the attraction coefficient. The presence of instability indicates that this type of equilibrium cluster does not correspond to the minimum energy in all directions and will be converted into another stable configuration. The universal magic number Nm of grains in one shell cluster, such that for N=Nm+1 the modes of the shell start to be unstable and the cluster converts to the cluster with Nm grains in the shell and one grain in the center, is found for both the Yukawa screening and for the nonlinear screening. A new experimental setup with remote hard-wall confinement is proposed for possible experimental investigation of boundary-free 2D clusters.
Three-centered model of ultrafast photoinduced charge transfer: Continuum dielectric approach
Authors: Khohlova Svetlana S. , Mikhailova Valentina A. , Ivanov Anatoly I.
Published: March 2006

A theoretical description of photoinduced charge transfer involves explicit treating both the optical formation of the nuclear wave packet on the excited free energy surface and its ensuing dynamics. The reaction pathway constitutes two-stage charge transfer between three centers. Manifestations of fractional charge transfer at first stage are explored. An expression for time dependent rate constant of photoinduced charge transfer is found in the framework of the linear dielectric continuum model of the medium. The model involves both the intramolecular vibrational reorganization and the Coulombic interaction of the transferred charge with the medium polarization fluctuations and allows to express the rate in terms of intramolecular reorganization parameters and complex dielectric permittivity. The influence of the vibrational coherent motion in the locally excited state on the charge transfer dynamics has been explored. The dependence of the ultrafast photoinduced charge transfer dynamics on the excitation pulse carrier frequency (spectral effect) has been investigated. The spectral effect has been shown to depend on quantity of the fractional charge.
The resistance peak of helicon plasmas at low magnetic fields
Authors: Cho Suwon
Published: March 2006

The dispersion characteristics of the radial eigenmodes and resistive loading of helicon plasmas are studied to explain the occurrence of the density peak at low magnetic fields. The plasma resistance is usually found to be large for the eigenmodes near the magnetic field where the fast and slow waves are coupled and can be peaked at low magnetic fields depending on the antenna configuration. It is explained how reflection of the waves at an axial end causes the resistance peak at low magnetic fields for a single loop antenna and the Nagoya type III or helical antenna itself can give rise to the resistance peak regardless of reflection. Finally, the dependence of the resistance peak on the density and the wave frequency is examined to show that the general trend is consistent with experimental observations.
Stabilization mechanism of edge states in graphene
Authors: Sasaki K. , Murakami S. , Saito R.
Published: March 2006

It has been known that edge states of a graphite ribbon are zero-energy, localized eigen-states. We show that next nearest-neighbor hopping process decreases the energy of the edge states at zigzag edge with respect to the Fermi energy. The energy reduction of the edge states is calculated analytically by first-order perturbation theory and numerically. The resultant model is consistent with the peak of recent scanning tunneling spectroscopy measurements.