bluuebunny/crossref_metadata_2025 huggingface dataset:
Does age at the time of elective cardiac surgery or catheter intervention in children influence the longitudinal development of psychological distress and styles of coping of parents?
Authors: Utens Elisabeth M. , Bieman Herma J. Versluis-Den , Witsenburg Maarten , Bogers Ad J.J.C. , Hess John , Verhulst Frank C.
Published: August 2006

Aims: To assess the influence of age at a cardiac procedure of children, who underwent elective cardiac surgery or interventional cardiac catheterisation for treatment of congenital cardiac defects between 3 months and 7 years of age, on the longitudinal development of psychological distress and styles of coping of their parents. Methods: We used the General Health Questionnaire to measure psychological distress, and the Utrecht Coping List to measure styles of coping. Parents completed questionnaires on average respectively 5 weeks prior to, and 18.7 months after, cardiac surgery or catheter intervention for their child. Results: Apart from one exception, no significant influence was found of the age at which children underwent elective cardiac surgery or catheter intervention on the pre- to postprocedural course of psychological distress and the styles of coping of their parents. Across time, parents of children undergoing surgery reported, on average, significantly higher levels of psychological distress than parents of children who underwent catheter intervention. After the procedure, parents of children who underwent either procedure reported significantly lower levels of psychological distress, and showed a weaker tendency to use several styles of coping, than did their reference groups. Conclusion: Age of the children at the time of elective cardiac surgery or catheter intervention did not influence the course of psychological distress of their parents, nor the styles of coping used by the parents. Future research should investigate in what way the age at which these cardiac procedures are performed influences the emotional and cognitive development of the children.
Bony density in adolescents after surgical repair of tetralogy of Fallot: a comparative study with healthy adolescents
Authors: Rego Carla , Guerra António , Guardiano Micaela , Esteves Patricia , Pereira Jorge , Aguiar Álvaro , Areias José Carlos
Published: August 2006

Background: Adverse influences arising in fetal life or immediately after birth have a permanent effect on body structure, physiology and metabolism. Evidence is now accumulating that programming of bone growth might be an important contributor to the later risk of osteoporosis. Long-term morbidity and mortality associated with tetralogy of Fallot is not completely known. The aim of the present study was to evaluate the state of the bones in adolescents after surgical repair of tetralogy of Fallot, so as to ascertain any possible repercussions of the disease on bone mineralization. Material and methods: We studied 34 adolescents with repaired tetralogy of Fallot, between the ages of 11 and 18 years, to establish their nutritional status, in terms of height, weight, and skinfolds, their body composition using an anthropometric method, their sexual maturity according to Tanner, and their food-habits as based on 24-hour recall. Bone density was evaluated by lumbar dual-energy X-ray absorptiometry. We included 34 healthy eutrophic adolescents, matched for gender and age, as controls. Results: No significant differences were observed between the patients and their controls concerning nutritional status, body composition, total energy intake and nutritional supply in macronutrients, calcium, phosphorus, magnesium and vitamin D. Bone mineral density, expressed in Z-score and g/cm2, was significantly higher in patients with tetralogy of Fallot (p < 0.01). The age at the time of the first surgical procedure, or at complete surgical repair, and the total number of surgical procedures, had no significant influence on nutritional status or bone mineralization. Gender, chronological age, sexual maturity and the index of body mass are the major determinants of bone density for both samples. Obese adolescents with repaired tetralogy of Fallot had a significantly higher bone density (p < 0.05) compared to undernourished or euthrophic patients. Conclusions: Being born with tetralogy of Fallot has no significant repercussion, by the stage of adolescence, on nutritional status, pubertal progression, and accretion of bone minerals subsequent to surgical repair. Nutritional status is the major influence on the accretion of bone mass.
Aerobic capacity in adults with tetralogy of Fallot
Authors: Fredriksen Per Morten , Therrien Judith , Veldtman Gruschen , Warsi Mohammed Ali , Liu Peter , Thaulow Erik , Webb Gary
Published: August 2006

Background: We investigated the aerobic capacity of 168 adult patients who had undergone successful surgical repair of tetralogy of Fallot at the University of Toronto Congenital Cardiac Centre for Adults. Methods: We compared values of peak uptake of oxygen, peak heart rate, forced vital capacity, and forced expiratory volume in 1 second to predicted values for their age groups. Results: The patients who had undergone surgical repair of tetralogy of Fallot demonstrated an overall diminished peak uptake of oxygen, at 51%, and peak heart rate, at 79%, compared to predicted values. No difference in peak aerobic capacity was found according to the initial surgical strategy of palliation or repair. Conclusions: Adult patients who have undergone surgical repair of tetralogy of Fallot have lower peak uptake of oxygen, and peak heart rate, compared to predicted values. The reduction in the peak heart rate may affect their exercise capacity. The peak uptake of oxygen also decreased with increasing age at the time of testing, and the age at surgical repair.
Acoustic Architecture: Music and Space in the Video Installations of Bill Viola
Authors: ROGERS HOLLY
Published: August 2006

Video installation art is a collaboration of sound, image, and space, with a closer relationship to music and art than to cinema. Accordingly, those working in this genre are often both artist and musician, a double role that represents a radical departure from the artist/musician divide of many other audio-visual genres. Because it is single authored, video installation can invert many elements of the filmmaking process: while it is common procedure to add a soundtrack to film during post-production, for instance, many video artists use sound as their starting point, often basing whole works on a musical structure. While such an inversion invites reconsideration of musical audibility and film narrative, video work, when installed, also challenges the notions of screen space and realism. An audience is no longer offered the single-point perspective of film, but is instead enveloped within a three-dimensional space. And as image expands beyond the four sides of the cinema screen – a space occupied previously by music alone – important questions are raised: what happens to music when film breaks from the containment of the screen? when it destroys its own boundaries? Focusing on the work of Bill Viola, this paper explores the ways in which video installation art confronts methods of film exhibition and audience engagement, and investigates how such confrontation redefines the roles of music and image in film.
Cool Charts or Barbertrash? Barbershop Harmony’s Flexible Concept of the Musical Work
Authors: GARNETT LIZ
Published: August 2006

This paper explores the ways in which the Barbershop Harmony Society’s flexible and contested constructions of musical content relate to the community’s originary myths, to its ongoing negotiations of social and organizational values, and to specific musical practices. Drawing on documentary evidence, interviews, and participant observation, I argue that barbershop’s rather fitful and intermittent espousal of a form of Werktreue ideal can best be understood in the context of the idiom’s characteristic approaches to music making. The theoretical fissures that riddle the Barbershop Harmony Society’s definitive discourses, meanwhile, reflect the tensions between different sets of musical and social values simultaneously in play among Society members. Recent debates within the Barbershop Harmony Society about membership levels, breadth of appeal, and repertoire consequently emerge as a tension between the ideals of Preservation and Encouragement that it was founded to promote.
Stephen Cottrell, Professional Music-Making in London: Ethnography and Experience (Aldershot: Ashgate, 2004), ISBN 0 7546 0887 5 (hb), 0 7546 0889 1 (pb)
Authors: Cornelius Steven
Published: August 2006

I read Stephen Cottrell's broad-ranging ethnography Professional Music-Making in London with both great interest and disquiet. Cottrell has made a significant scholarly contribution in successfully outlining the myriad social, political, economic, and artistic forces that comprise that city's classical music performance culture. His model, which offers potential bridges between ethnomusicology and musicology, will prove useful in any number of locales and theoretical studies. My disquiet arose from the fact that the author details a musical world of frustration, dead ends, and downright failure. Twenty years ago, and an ocean away, I escaped a similar professional existence in New York City.
Adhärenz, pharmakokinetischer «Toleranzbereich» und HIV-Resistenzbildung
Authors: Mossdorf  , Hirsch
Published: August 2006

Anlässlich einer Kontrolle wird bei einem 43-jährigen, HIV-positiven Patienten mit ART neu eine HIV-Viruslast von 2032 Kopien/mL festgestellt. Zuvor war unter einer Therapie mit Lamivudin und Zidovudin (NRTI) sowie Nelfinavir (nicht-geboosteter PI) die Viruslast während 18 Monaten undetektierbar (< 50 Kopien/mL). Es konnte die Diagnose einer sekundären HIV-Resistenz des ungeboosteten PIs bei pharmakokinetischer Non-Adhärenz gestellt werden. Die HIV-Resistenzprüfung legte eine Salvage-Therapie mit einem geboosteten PI nahe. Neben der regelmässigen Medikamenteneinnahme erbringen diese antiretroviralen Medikamente mit ihren hohen Serumspiegeln und langen Halbwertszeiten eine dauerhafte Virussuppression und vermindern das Risiko von Resistenzentwicklungen.
Influence of rheology on realignment of mantle convective structure with plate motion after a plate reorganization
Authors: van Hunen J. , Zhong S.
Published: August 2006

Small‐scale convection (SSC) rolls below the oceanic lithosphere have the tendency to align with the large‐scale shearing direction and thus with the plate motion direction relative to the deep mantle. Understanding the timescales of and processes responsible for realignment would contribute significantly to our understanding of the unresolved phenomena in the Pacific such as gravity lineations, small‐scale seismic velocity variations, and intraplate volcanism that cannot be explained by hot spots. In this study we examine the evolution of those convection rolls when this relative plate motion direction is suddenly changed, as suggested by the kink in the Hawaii‐Emperor seamount chain. Using three‐dimensional numerical flow models, we investigate the realignment of SSC rolls after a change in plate motion direction. From the nature of the SSC, it is expected that rheological parameters dominate the characteristics of this realignment. Our results show that this is indeed the case. We find that (1) using constraints from onset timing of SSC, realignment of rolls can occur as fast as within 20 Ma, but might also take much longer, dependent on the rheology; (2) the realignment period is strongly correlated to the sum of large‐scale shear stress induced by plate motion and small‐scale shear stress from the SSC itself; (3) in a mantle deforming by dislocation creep, realignment occurs faster than by diffusion creep, because dislocation creep SSC is more vigorous; and (4) activation energy has little influence on the realignment time. Possible evidence for the realignment period might come from precise age determination of intraplate volcanism or azimuthal seismic anisotropy.
Glacial/interglacial changes in southern Africa: Compound‐specific δ13C land plant biomarker and pollen records from southeast Atlantic continental margin sediments
Authors: Rommerskirchen Florian , Eglinton Geoffrey , Dupont Lydie , Rullkötter Jürgen
Published: August 2006

This is part 2 of a study examining southwest African continental margin sediments from nine sites on a north‐south transect from the Congo Fan (4°S) to the Cape Basin (30°S) representing two glacial (MIS 2 and 6a) and two interglacial stages (MIS 1 and 5e). Contents, distribution patterns, and molecular stable carbon isotope signatures of long‐chain n‐alkanes (C27‐C33) and n‐alkanols (C22‐C32) as indicators of land plant vegetation of different biosynthetic types were correlated with concentrations and distributions of pollen taxa in sediments of the same time horizons. Selected single pollen type data reveal details of vegetation changes, but the overall picture is best illustrated by summing pollen known to predominantly derive from C4 plants or C4 plus CAM plants. The C4 plant signals in the biomarkers are recorded in the δ13C data and in the abundances of C31 and C33n‐alkanes, and the C32n‐alkanol. Calculated clusters of wind trajectories for austral summer and winter situations for the Holocene and the Last Glacial Maximum afford information on the source areas for the lipids and pollen and their transport pathways to the ocean. This multidisciplinary approach provides clear evidence of latitudinal differences in leaf wax lipid and pollen composition, with the Holocene sedimentary data paralleling the current major phytogeographic zonations. The northern sites (Congo Fan area and northern Angola Basin) get most of their terrestrial material from the Congo Basin and the Angolan highlands dominated by C3 plants. Airborne particulates derived from the western and central South African hinterland dominated by deserts, semideserts, and savannah regions are rich in organic matter from C4 plants. As can be expected from the present and glacial positions of the phytogeographic zones, the carbon isotopic signatures of n‐alkanes and n‐alkanols both become isotopically more enriched in 13C from north to south. In the northern part of the transect the relative importance of C4 plant indicators is higher during the glacials than in the interglacials, indicating a northward extension of arid zones favoring grass vegetation. In the south, where grass‐rich vegetation merges into semidesert and desert, the difference in C4 plant indicators is small.
Contrasts in sea ice deformation and production in the Arctic seasonal and perennial ice zones
Authors: Kwok R.
Published: August 2006

Four years (1997–2000) of RADARSAT Geophysical Processor System (RGPS) data are used to contrast the sea ice deformation and production regionally, and in the seasonal (SIZ) and perennial (PIZ) ice zones. Ice production is of seasonal ice in openings during the winter. Three‐day estimates of these quantities are provided within Lagrangian elements initially 10 km on a side. A distinct seasonal cycle is seen in both zones with these estimates highest in the late fall and with seasonal minimums in the midwinter. Regional divergence over the winter could be up to 30%. Spatially, the highest deformation is seen in the SIZ north of coastal Alaska. Both ice deformation and production are higher in the SIZ: deformation‐related ice production in the SIZ (∼0.5 m) is 1.5–2.3 times that of the PIZ (∼0.3 m): this is connected to ice strength and thickness. Atmospheric forcing and boundary layer structure contribute to only the seasonal and interannual variability. Seasonal ice growth in ice fractures accounts for ∼25–40% of the total ice production of the Arctic Ocean. Uncertainties in these estimates are discussed. By itself, this deformation‐ice production relationship could be considered a negative feedback when thickness is perturbed. However, the overall effect on ice production in the face of increasing seasonal and thinner/weaker ice coverage could be modified by local destabilization of the water column promoting overturning of warmer water due to increased brine rejection; and the upwelling of the pynocline associated with increased occurrence of large shear motion in sea ice. Divergence is shown to be negligibly correlated to cyclonic motion in summer and winter in both ice zones.
Quantifying sulfate components and their variations in soils of the McMurdo Dry Valleys, Antarctica
Authors: Bao Huiming , Marchant David R.
Published: August 2006

Many soils of the McMurdo Dry Valleys (MDV), Antarctica, being old, hyperarid, and frigid, have accumulated abundant atmospheric salts over the last several million years. This salt repository offers an opportunity to study atmospheric chemistry (past and present), the origin and transport of ions in soils, the weathering activity of soils, and postdepositional soil‐leaching processes within this unique environment. In particular, soil sulfate in the MDV is known to have multiple origins, but the precise proportions of different sulfate components remain elusive. Here we test a hypothesis that soil sulfate in the MDV is a predictable mixture of three major components: sea‐salt sulfate, non‐sea‐salt sulfate, and background sulfate (derived from weathering and volcanic sources) that to a large extent, varies as a function of elevation and distance from the coast. By measuring sulfate's three stable isotope parameters, i.e., Δ17O, δ18O, and δ34S, plus estimating independently the end‐member stable isotope parameters for the three components on the basis of published reports and our measured data, we solve explicitly the mixing proportion for each component using a set of three simultaneous linear equations. The results from four spatially representative soil profiles show that the sum of such calculated proportions for the three components is very close to unity in most samples, suggesting that a simple three‐component mixing model is a good representation of the soil sulfate budget. While significant uncertainties still exist in the isotope compositions of different sulfate end‐members, these data provide important initial constraints on sulfate diversity as well as its spatial and vertical distribution in the MDV.
Eastern Pacific Warm Pool paleosalinity and climate variability: 0–30 kyr
Authors: Benway H. M. , Mix A. C. , Haley B. A. , Klinkhammer G. P.
Published: August 2006

Multiproxy geologic records of δ18O and Mg/Ca in fossil foraminifera from sediments under the Eastern Pacific Warm Pool (EPWP) region west of Central America document variations in upper ocean temperature, pycnocline strength, and salinity (i.e., net precipitation) over the past 30 kyr. Although evident in the paleotemperature record, there is no glacial‐interglacial difference in paleosalinity, suggesting that tropical hydrologic changes do not respond passively to high‐latitude ice sheets and oceans. Millennial variations in paleosalinity with amplitudes as high as ∼4 practical salinity units occur with a dominant period of ∼3–5 ky during the glacial/deglacial interval and ∼1.0–1.5 ky during the Holocene. The amplitude of the EPWP paleosalinity changes greatly exceeds that of published Caribbean and western tropical Pacific paleosalinity records. EPWP paleosalinity changes correspond to millennial‐scale climate changes in the surface and deep Atlantic and the high northern latitudes, with generally higher (lower) paleosalinity during cold (warm) events. In addition to Intertropical Convergence Zone (ITCZ) dynamics, which play an important role in tropical hydrologic variability, changes in Atlantic‐Pacific moisture transport, which is closely linked to ITCZ dynamics, may also contribute to hydrologic variations in the EPWP. Calculations of interbasin salinity average and interbasin salinity contrast between the EPWP and the Caribbean help differentiate long‐term changes in mean ITCZ position and Atlantic‐Pacific moisture transport, respectively.
Determination of temperature‐dependent stable strontium isotope (88Sr/86Sr) fractionation via bracketing standard MC‐ICP‐MS
Authors: Fietzke J. , Eisenhauer A.
Published: August 2006

Stable strontium isotopes (here 88Sr/86Sr) are introduced as a new member of the nontraditional stable isotopes. We have developed a bracketing standard method for the determination of δ88/86Sr using an AXIOM MC‐ICP‐MS and normalizing to strontium SRM NBS987. For individual measurements the external reproducibility is better than about 25 ppm (1σ RSD). For the IAPSO seawater standard a δ88/86Sr value of 0. 381 ± 0.010‰ (2SEM) was determined. For the first time a temperature‐dependent strontium isotope fractionation during calcium carbonate precipitation could be shown. Aragonite samples inorganically precipitated under temperature control between 10 and 50°C revealed a δ88/86Sr/temperature dependency of 0.0054(5)‰/°C (R2 = 0.987). In contrast, for natural coral samples (Pavona clavus) from a proxy calibration study (23 to 27°C) we did determine 0.033(5)‰/°C (R2 = 0.955). The processes causing this sixfold stronger temperature dependency for the natural coral samples have to be studied in more detail in future studies. In a first approach the different slopes can be interpreted as effects of kinetic fractionation of strontium ions with or without a hydrate shell of 22 to 29 water molecules.
Significant vertical water transport by mountain‐induced circulations on Mars
Authors: Michaels T. I. , Colaprete A. , Rafkin S. C. R.
Published: August 2006

Using a 3‐D, non‐hydrostatic mesoscale Mars atmospheric model with detailed aerosol/cloud microphysics, we show that the formation of discrete afternoon clouds over the Olympus Mons volcano is due to the symbiosis of upslope thermal flow and a lee mountain wave circulation, and that these clouds exhibit complex particle distributions. Furthermore, we illustrate that this and other mountain‐induced circulations transport large quantities of dust, water vapor, and water ice aerosol from lower altitudes into the free atmosphere general circulation. Therefore, these circulations are an important part of Mars' net Hadley circulation and climatic forcing.
High‐resolution estimates of Australia's coastal population
Authors: Chen Keping , McAneney John
Published: August 2006

Here we quantify Australian coastal population at a spatial resolution of 1 km and do this as a function of distance to shoreline and elevation above mean sea level. We also report comprehensive validations based on statistical and spatial relationships between very fine‐resolution Australian data sets and the recent high‐resolution global data sets on ambient population distribution (LandScan2003), shorelines (GSHHS) and elevation (SRTM). Estimates are heavily dependent upon the resolutions of all input data, as well as the resolution of analysis. Our results show about 50% of Australian addresses or population are located within 7 km of the shore, and that population decreases very rapidly with increasing distance from the shoreline. About 6.0% of Australian addresses are situated within 3 km of shorelines in areas with elevations below 5 m.
An observation‐based estimate of the strength of rainfall‐vegetation interactions in the Sahel
Authors: Los S. O. , Weedon G. P. , North P. R. J. , Kaduk J. D. , Taylor C. M. , Cox P. M.
Published: August 2006

Over the course of the twentieth century the African Sahel experienced large variations in annual precipitation; including the wet period during the 1950s and 1960s and the long‐term drought during the 1970s and 1980s. Feedbacks between the land surface and atmosphere can affect rainfall variability at monthly, annual and decadal time scales. However, the strength of the coupling between the land surface and precipitation is still highly uncertain, with climate‐model derived estimates differing by an order of magnitude. Here a statistical model of vegetation greenness is used to estimate the vegetation‐rainfall coupling strength in the Sahel, based on monthly satellite‐derived vegetation index and meteorological data. Evidence is found for a positive feedback between vegetation and rainfall at the monthly time scale, and for a vegetation memory operating at the annual time scale. These vegetation‐rainfall interactions increase the interannual variation in Sahelian precipitation; accounting for as much as 30% of the variability in annual precipitation in some hot spot regions between 15° and 20°N.
Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
Authors: Garcerá Ana , Barreto Lina , Piedrafita Lidia , Tamarit Jordi , Herrero Enrique
Published: August 2006

The Saccharomyces cerevisiae genome encodes three proteins that display similarities with human GSTOs (Omega class glutathione S-transferases) hGSTO1-1 and hGSTO2-2. The three yeast proteins have been named Gto1, Gto2 and Gto3, and their purified recombinant forms are active as thiol transferases (glutaredoxins) against HED (β-hydroxyethyl disulphide), as dehydroascorbate reductases and as dimethylarsinic acid reductases, while they are not active against the standard GST substrate CDNB (1-chloro-2,4-dinitrobenzene). Their glutaredoxin activity is also detectable in yeast cell extracts. The enzyme activity characteristics of the Gto proteins contrast with those of another yeast GST, Gtt1. The latter is active against CDNB and also displays glutathione peroxidase activity against organic hydroperoxides such as cumene hydroperoxide, but is not active as a thiol transferase. Analysis of point mutants derived from wild-type Gto2 indicates that, among the three cysteine residues of the molecule, only the residue at position 46 is required for the glutaredoxin activity. This indicates that the thiol transferase acts through a monothiol mechanism. Replacing the active site of the yeast monothiol glutaredoxin Grx5 with the proposed Gto2 active site containing Cys46 allows Grx5 to retain some activity against HED. Therefore the residues adjacent to the respective active cysteine residues in Gto2 and Grx5 are important determinants for the thiol transferase activity against small disulphide-containing molecules.
Ras activation in response to phorbol ester proceeds independently of the EGFR via an unconventional nucleotide-exchange factor system in COS-7 cells
Authors: Rubio Ignacio , Rennert Knut , Wittig Ute , Beer Katrin , Dürst Matthias , Stang Stacey L. , Stone Jim , Wetzker Reinhard
Published: August 2006

Ras is a major mediator of PE (phorbol ester) effects in mammalian cells. Various mechanisms for PE activation of Ras have been reported [Downward, Graves, Warne, Rayter and Cantrell (1990) Nature (London) 346, 719–723; Shu, Wu, Mosteller and Broek (2002) Mol. Cell. Biol. 22, 7758–7768; Roose, Mollenauer, Gupta, Stone and Weiss (2005) Mol. Cell. Biol. 25, 4426–4441; Grosse, Roelle, Herrlich, Höhn and Gudermann (2000) J. Biol. Chem. 275, 12251–12260], including pathways that target GAPs (GTPase-activating proteins) for inactivation and those that result in activation of GEFs (guanine nucleotide-exchange factors) Sos (son of sevenless homologue) or RasGRP (RAS guanyl releasing protein). However, a biochemical link between PE and GAP inactivation is missing and GEF stimulation is hard to reconcile with the observation that dominant-negative S17N-Ras does not compromise Ras-dependent ERK (extracellular-signal-regulated kinase) activation by PE. We have addressed this controversy and carried out an in-depth biochemical study of PE-induced Ras activation in COS-7 cells. Using a cell-permeabilization approach to monitor nucleotide exchange on Ras, we demonstrate that PE-induced Ras-GTP accumulation results from GEF stimulation. Nucleotide exchange stimulation by PE is prevented by PKC (protein kinase C) inhibition but not by EGFR [EGF (epidermal growth factor) receptor] blockade, despite the fact that EGFR inhibition aborts basal and PE-induced Shc (Src homology and collagen homology) phosphorylation and Shc–Grb2 (growth-factor-receptor-bound protein 2) association. In fact, EGFR inhibition ablates basal nucleotide exchange on Ras in growth-arrested COS-7 cells. These data disclose the existence of two separate GEF systems that operate independently from each other to accomplish PE-dependent formation of Ras-GTP and to maintain resting Ras-GTP levels respectively. We document that COS-7 cells do not express RasGRP and present evidence that the PE-responsive GEF system may involve PKC-dependent phosphorylation of Sos. More fundamentally, these observations shed new light on enigmatic issues such as the inefficacy of S17N-Ras in blocking PE action or the role of the EGFR in heterologous agonist activation of the Ras/ERK pathway.
Endogenous ADP-ribose enables calcium-regulated cation currents through TRPM2 channels in neutrophil granulocytes
Authors: Heiner Inka , Eisfeld Jörg , Warnstedt Maike , Radukina Natalia , Jüngling Eberhard , Lückhoff Andreas
Published: August 2006

TRPM2 (transient receptor potential melastatin 2) is a Ca2+-permeable cation channel gated by ADPR (ADP-ribose) from the cytosolic side. To test whether endogenous concentrations of intracellular ADPR are sufficient for TRPM2 gating in neutrophil granulocytes, we devised an HPLC method to determine ADPR contents in HClO4 cell extracts. The reversed-phase ion-pair HPLC method with an Mg2+-containing isocratic eluent allows baseline resolution of one ADPR peak. Intracellular ADPR concentrations were approx. 5 μM in granulocytes and not significantly altered by stimulation with the chemoattractant peptide fMLP (N-formylmethionyl-leucylphenylalanine). We furthermore determined intracellular concentrations of cADPR (cyclic ADPR) with a cyclase assay involving enzymatic conversion of cADPR into NAD+ and fluorimetric determination of NAD+. Intracellular cADPR concentrations were approx. 0.2 μM and not altered by fMLP. In patch–clamp experiments, ADPR (0.1–100 μM) was dialysed into granulocytes to analyse its effects on whole-cell currents characteristic for TRPM2, in the presence of a low (<10 nM) or a high (1 μM) intracellular Ca2+ concentration. TRPM2 currents were significantly larger at high than at low [Ca2+] (e.g. −225±27.1 versus −7±2.0 pA/pF at 5 μM ADPR), but no currents at all were observed in the absence of ADPR (ADPR concentration ≤0.3 μM). cADPR (0.1, 0.3 and 10 μM) was without effect even in the presence of subthreshold ADPR (0.1 μM). We conclude that ADPR enables an effective regulation of TRPM2 by cytosolic Ca2+. Thus ADPR and Ca2+ in concert behave as a messenger system for agonist-induced influx of Ca2+ through TRPM2 in granulocytes.
Polyamine-modulated c-Myc expression in normal intestinal epithelial cells regulates p21Cip1 transcription through a proximal promoter region
Authors: Liu Lan , Guo Xin , Rao Jaladanki N. , Zou Tongtong , Marasa Bernard S. , Chen Jie , Greenspon Jose , Casero Robert A. , Wang Jian-Ying
Published: August 2006

Maintenance of intestinal mucosal epithelial integrity requires cellular polyamines that regulate expression of various genes involved in cell proliferation, growth arrest and apoptosis. Our previous studies have shown that polyamines are essential for expression of the c-myc gene and that polyamine-induced c-Myc plays a critical role in stimulation of normal IEC (intestinal epithelial cell) proliferation, but the exact downstream targets of induced c-Myc are still unclear. The p21Cip1 protein is a major player in cell cycle control, which is primarily regulated at the transcriptional level. The current study was designed to determine whether induced c-Myc stimulates normal IEC proliferation by repressing p21Cip1 transcription following up-regulation of polyamines. Overexpression of the ODC (ornithine decarboxylase) gene increased levels of cellular polyamines, induced c-Myc expression and inhibited p21Cip1 transcription, as indicated by repression of p21Cip1 promoter activity and a decrease in p21Cip1 protein levels. In contrast, depletion of cellular polyamines by inhibiting ODC enzyme activity with α-difluoromethylornithine decreased c-Myc, but increased p21Cip1 transcription. Ectopic expression of wild-type c-myc not only inhibited basal levels of p21Cip1 transcription in control cells, but also prevented increased p21Cip1 in polyamine-deficient cells. Experiments using different p21Cip1 promoter mutants showed that transcriptional repression of p21Cip1 by c-Myc was mediated through Miz-1- and Sp1-binding sites within the proximal region of the p21Cip1 promoter in normal IECs. These findings confirm that p21Cip1 is one of the direct mediators of induced c-Myc following increased polyamines and that p21Cip1 repression by c-Myc is implicated in stimulation of normal IEC proliferation.
Identification and functional characterization of hCLS1, a human cardiolipin synthase localized in mitochondria
Authors: Chen Daohong , Zhang Xing-Yue , Shi Yuguang
Published: August 2006

In eukaryotic cells, CLS (cardiolipin synthase) is involved in the final step of cardiolipin synthesis by catalysing the transfer of a phosphatidyl residue from CDP-DAG (diacylglycerol) to PG (phosphatidylglycerol). Despite an important role of cardiolipin in regulating mitochondrial function, a gene encoding the mammalian CLS has not been identified so far. We report in the present study the identification and characterization of a human cDNA encoding the first mammalian CLS [hCLS1 (human CLS1)]. The predicted hCLS1 peptide sequence shares significant homology with the yeast and plant CLS proteins. The recombinant hCLS1 enzyme expressed in COS-7 cells catalysed efficiently the synthesis of cardiolipin in vitro using CDP-DAG and PG as substrates. Furthermore, overexpression of hCLS1 cDNA in COS-7 cells resulted in a significant increase in cardiolipin synthesis in intact COS-7 cells without any significant effects on the activity of the endogenous phosphatidylglycerophosphate synthase of the transfected COS-7 cells. Immunohistochemical analysis demonstrated that the recombinant hCLS1 protein was localized to the mitochondria when transiently expressed in COS-7 cells, which was further corroborated by results from subcellular fractionation analyses of the recombinant hCLS1 protein. Northern-blot analysis showed that the hCLS1 gene was predominantly expressed in tissues that require high levels of mitochondrial activities for energy metabolism, with the highest expression in skeletal and cardiac muscles. High levels of hCLS1 expression were also detected in liver, pancreas, kidney and small intestine, implying a functional role of hCLS1 in these tissues.
Phosphorylation of hepatitis B virus Cp at Ser87 facilitates core assembly
Authors: Kang Hee Yong , Lee Seungkeun , Park Sung Gyoo , Yu Jaehoon , Kim Youngsoo , Jung Guhung
Published: August 2006

Protein–protein interactions can be regulated by protein modifications such as phosphorylation. Some of the phosphorylation sites (Ser155, Ser162 and Ser170) of HBV (hepatitis B virus) Cp have been discovered and these sites are implicated in the regulation of viral genome encapsidation, capsid localization and nucleocapsid maturation. In the present report, the dimeric form of HBV Cp was phosphorylated by PKA (protein kinase A), but not by protein kinase C in vitro, and the phosphorylation of dimeric Cp facilitated HBV core assembly. Matrix-assisted laser-desorption ionization–time-of-flight analysis revealed that the HBV Cp was phosphorylated at Ser87 by PKA. This was further confirmed using a mutant HBV Cp with S87G mutation. The S87G mutation inhibited the phosphorylation and, as a result, the in vitro HBV core assembly was not facilitated by PKA. In addition, when either pCMV/FLAG–Core(WT) or pCMV/FLAG–Core(S87G) was transfected into HepG2 cells, few mutant Cps (S87G) assembled into capsids compared with the wild-type (WT) Cps, although the same level of total Cps was expressed in both cases. In conclusion, PKA facilitates HBV core assembly through phosphorylation of the HBV Cp at Ser87.
Inhibition of MEK/ERK1/2 signalling alters endothelial nitric oxide synthase activity in an agonist-dependent manner
Authors: Cale Jacqueline M. , Bird Ian M.
Published: August 2006

eNOS (endothelial nitric oxide synthase) activity is post-translationally regulated in a complex fashion by acylation, protein–protein interactions, intracellular trafficking and phosphorylation, among others. Signalling pathways that regulate eNOS activity include phosphoinositide 3-kinase/Akt, cyclic nucleotide-dependent kinases [PKA (protein kinase A) and PKG], PKC, as well as ERKs (extracellular-signal-regulated kinases). The role of ERKs in eNOS activation remains controversial. In the present study, we have examined the role of ERK1/2 in eNOS activation in HUVEC-CS [transformed HUVEC (human umbilical-vein endothelial cells)] as well as a widely used model for eNOS study, transiently transfected COS-7 cells. U0126 pretreatment of HUVEC-CS potentiated ATP-stimulated eNOS activity, independent of changes in intracellular Ca2+ concentration ([Ca2+]i). In COS-7 cells transiently expressing ovine eNOS, U0126 potentiated A23187-stimulated eNOS activity, but inhibited ATP-stimulated activity. Compensatory changes in phosphorylation of five key eNOS residues did not account for changes in A23187-stimulated activity. However, in the case of ATP, altered phosphorylation and changes in [Ca2+]i may partially contribute to U0126 inhibition of activity. Finally, seven eNOS alanine mutants of putative ERK1/2 targets were generated and the effects of U0126 pretreatment on eNOS activity were gauged with A23187 and ATP treatment. T97A-eNOS was the only construct significantly different from wild-type after U0126 pretreatment and ATP stimulation of eNOS activation. In the present study, eNOS activity was either potentiated or inhibited in COS-7 cells, suggesting agonist dependence for MEK/ERK1/2 signalling [where MEK is MAPK (mitogen-activated protein kinase)/ERK kinase] to eNOS and a complex mechanism including [Ca2+]i, phosphorylation and, possibly, intracellular trafficking.
Regulatory circuits controlling white versus brown adipocyte differentiation
Authors: Hansen Jacob B. , Kristiansen Karsten
Published: August 2006

Adipose tissue is a major endocrine organ that exerts a profound influence on whole-body homoeostasis. Two types of adipose tissue exist in mammals: WAT (white adipose tissue) and BAT (brown adipose tissue). WAT stores energy and is the largest energy reserve in mammals, whereas BAT, expressing UCP1 (uncoupling protein 1), can dissipate energy through adaptive thermogenesis. In rodents, ample evidence supports BAT as an organ counteracting obesity, whereas less is known about the presence and significance of BAT in humans. Despite the different functions of white and brown adipocytes, knowledge of factors differentially influencing the formation of white and brown fat cells is sparse. Here we summarize recent progress in the molecular understanding of white versus brown adipocyte differentiation, including novel insights into transcriptional and signal transduction pathways. Since expression of UCP1 is the hallmark of BAT and a key factor determining energy expenditure, we also review conditions associated with enhanced energy expenditure and UCP1 expression in WAT that may provide information on processes involved in brown adipocyte differentiation.
Identification of three crucial histidine residues (His115, His132 and His297) in porcine deoxyribonuclease II
Authors: Cheng Yu-Che , Hsueh Chin-Chen , Lu Shao-Chun , Liao Ta-Hsiu
Published: August 2006

DNase II is an acid endonuclease that is involved in the degradation of exogenous DNA and is important for DNA fragmentation and degradation during cell death. In an effort to understand its catalytic mechanism, we constructed plasmids encoding nine different histidine (H)-to-leucine (L) mutants for porcine DNase II and examined the enzyme properties of the expressed mutant proteins. Of the mutants, all but H132L were secreted into the medium of expressing cells. Six of the mutated DNase II proteins (H41L, H109L, H206L, H207L, H274L and H322L) showed enzyme activity, whereas the H115L, H132L and H297L mutants exhibited very little activity. The H115L and H297L mutants were found to undergo correct protein folding, but were inactive. To further examine these mutants, we expressed H115A and H297A DNase II mutants; these mutants were inactive, but their DNase activities could be rescued with imidazole, indicating that His115 and His297 are likely to function as a general acid and a general base respectively in the catalytic centre of the enzyme. In contrast with the secreted mutants, the H132L mutant protein was found in cell lysates within 16 h after transfection. This protein was inactive, improperly folded and was drastically degraded via the proteosomal pathway after 24 h. The polypeptide of another substitution for His132 with lysine resulted in the misfolded form being retained in endoplasmic reticulum.
Body composition and the apoB/apoA-I ratio in migrant Asian Indians and white Caucasians in Canada
Authors: Smith Jessica , Cianflone Katherine , Al-Amri Maha , Sniderman Allan
Published: August 2006

Migrant and native South Asians appear to be at increased risk of Type II diabetes mellitus and coronary disease. The aim of the present study was to determine the relationship between the most accurate summary index of the lipoprotein-related risk of vascular disease, the apoB (apolipoprotein B-100)/apoA-I (apolipoprotein A-I) ratio, and body composition in established migrant South Asians and white Caucasians living in Canada. Men and women living in Montreal, Canada between the ages of 20–60 years were recruited for participation in the study. Subjects were excluded if they had a history of cardiovascular disease or were taking lipid-lowering medication. Individuals identified themselves as Asian Indian or Caucasian. Anthropometric measurements were collected, including weight, height, waist circumference, hip circumference and body fat percentage. Plasma samples were analysed for total cholesterol, HDL-C (high-density lipoprotein-cholesterol), apoA-I and apoB. Indian subjects had a substantially higher WHR (waist-to-hip ratio) than Caucasian subjects [men, 0.93±0.01 compared with 0.86±0.01 respectively (P<0.001); women, 0.88±0.01 compared with 0.77±0.01 respectively (P<0.0001)]. WHR correlated strongly with body fat percentage in Caucasians (men, r=0.63, P=0.0002; women, r=0.74, P<0.0001). By contrast, there was no correlation in Indians (men, r=0.22, P value not significant; women, r=0.23, P value not significant). In addition, Indian men and women had a higher apoB/A-I ratio than Caucasians [men, 0.85±0.04 compared with 0.66±0.04 respectively (P=0.001); women, 0.73±0.04 compared with 0.56±0.03 respectively (P=0.0003)]. Of interest, there were also significant correlations between the apoB/apoA-I ratio and WHR in all of the groups, except the Indian women, which were stronger than the correlation of the apoB/apoA-I ratio with BMI. On the other hand, there was no significant relationship between the apoB/apoA-I ratio and the body fat percentage in any of the groups. In conclusion, the present study confirms that, as body fat percentage increases, the distribution of body fat differs between migrant Indians and Caucasians living in Canada. It also relates differences in body fat distribution to differences in the apoB/apoA-I ratio, providing at least part of the answer as to why South Asians may be at increased risk of vascular disease.
Are the lipid-modifying effects of fibrates mediated by alterations in plasma lipid transfer activity?
Authors: Lewis Gary F.
Published: August 2006

Fenofibrate, a PPAR-α (peroxisome-proliferator-activated receptor-α) agonist, has been shown to modify plasma lipid and lipoprotein composition and metabolism by a variety of mechanisms. In addition, fenofibrate has been shown to increase the activity of PLTP (phospholipid transfer protein) and to reduce the activity of CETP (cholesteryl ester transfer protein). It is not known, however, whether the changes in PLTP and CETP plasma activity play an active role in the lipid changes observed with fenofibrate therapy, and this is investigated by Watts and co-workers in the present issue of Clinical Science.
Photoelectron spectroscopy of large (water)n− (n=50–200) clusters at 4.7eV
Authors: Kammrath Aster , Verlet Jan R. R. , Griffin Graham B. , Neumark Daniel M.
Published: August 2006

Photoelectron spectra of large anionic water clusters are recorded at a photodetachment energy of 4.7eV. Two isomers are observed, as previously reported at 3.1eV. No evidence of a more tightly bound isomer is recovered.
Low dark current metal-semiconductor-metal photodiodes based on semi-insulating GaN
Authors: Butun Serkan , Gökkavas Mutlu , Yu HongBo , Ozbay Ekmel
Published: August 2006

Metal-semiconductor-metal photodetectors on semi-insulating GaN templates were demonstrated and compared with photodetectors fabricated on regular GaN templates. Samples were grown on a metal organic chemical vapor deposition system. Devices on semi-insulating template exhibited a dark current density of 1.96×10−10A∕cm2 at 50V bias, which is four orders of magnitude lower compared with devices on regular template. Device responsivities were 101.80 and 88.63A∕W at 50V bias for 360nm ultraviolet illumination for semi-insulating and regular templates, respectively. Incident power as low as 3pW was detectable using the devices that were fabricated on the semi-insulating template.
Some physical applications of fractional Schrödinger equation
Authors: Guo Xiaoyi , Xu Mingyu
Published: August 2006

The fractional Schrödinger equation is solved for a free particle and for an infinite square potential well. The fundamental solution of the Cauchy problem for a free particle, the energy levels and the normalized wave functions of a particle in a potential well are obtained. In the barrier penetration problem, the reflection coefficient and transmission coefficient of a particle from a rectangular potential wall is determined. In the quantum scattering problem, according to the fractional Schrödinger equation, the Green’s function of the Lippmann-Schwinger integral equation is given.
Direct computation of general chemical energy differences: Application to ionization potentials, excitation, and bond energies
Authors: Beste A. , Harrison R. J. , Yanai T.
Published: August 2006

Chemists are mainly interested in energy differences. In contrast, most quantum chemical methods yield the total energy which is a large number compared to the difference and has therefore to be computed to a higher relative precision than would be necessary for the difference alone. Hence, it is desirable to compute energy differences directly, thereby avoiding the precision problem. Whenever it is possible to find a parameter which transforms smoothly from an initial to a final state, the energy difference can be obtained by integrating the energy derivative with respect to that parameter (cf. thermodynamic integration or adiabatic connection methods). If the dependence on the parameter is predominantly linear, accurate results can be obtained by single-point integration. In density functional theory and Hartree-Fock, we applied the formalism to ionization potentials, excitation energies, and chemical bond breaking. Example calculations for ionization potentials and excitation energies showed that accurate results could be obtained with a linear estimate. For breaking bonds, we introduce a nongeometrical parameter which gradually turns the interaction between two fragments of a molecule on. The interaction changes the potentials used to determine the orbitals as well as the constraint on the orbitals to be orthogonal.