bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristic neurocognitive profile associated with adult attention-deficit/hyperactivity disorder
Authors: McLEAN A. , DOWSON J. , TOONE B. , YOUNG S. , BAZANIS E. , ROBBINS T. W. , SAHAKIAN B. J.
Published: May 2005

Background. It is now accepted that attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. However, relative to the considerable literature concerning the profile of neurocognitive deficits associated with this disorder in childhood, equivalent investigations in adult populations have been less common. The current study examined cognitive function in adults diagnosed with ADHD employing well-validated neuropsychological tasks.

Method. Nineteen adult patients who satisfied DSM-IV criteria for ADHD and 19 matched (gender, age and verbal IQ), non-clinical control subjects were recruited. Patients were either unmedicated or had abstained from a psychostimulant medication regime for at least 24 h prior to neurocognitive assessment. A functionally wide-ranging test battery was administered.

Results. Relative to controls, ADHD adults performed significantly worse on spatial working memory, planning, and attentional-set shifting tests and were significantly slower to respond to target stimuli on the go/no-go task. In contrast, the two subject groups performed equivalently on decision-making and pattern/spatial recognition memory assessments.

Conclusions. The demonstration of neuropsychological dysfunction in the adult ADHD cohort provides some support for the validity of this diagnosis in adulthood. In particular, there is broad consistency between the cognitive profile revealed in the current investigation and that previously demonstrated in a study of medication-naïve ADHD children. There is evidence that frontostriatal function is especially disrupted.
Prevalence, co-morbidity and correlates of mental disorders in the general population: results from the German Health Interview and Examination Survey (GHS)
Authors: JACOBI F. , WITTCHEN H.-U. , HÖLTING C. , HÖFLER M. , PFISTER H. , MÜLLER N. , LIEB R.
Published: May 2005

Background. The German National Health Interview and Examination Survey (GHS) is the first government mandated nationwide study to investigate jointly the prevalence of somatic and mental disorders within one study in the general adult population in Germany. This paper reports results from its Mental Health Supplement (GHS-MHS) on 4-week 12-month, and selected lifetime prevalence of a broad range of DSM-IV mental disorders, their co-morbidity and correlates in the community.

Methods. The sample of the GHS-MHS (n=4181; multistage stratified random sample drawn from population registries; conditional response rate: 87·6%) can be regarded as representative for the German population aged 18–65. Diagnoses are based on fully structured computer assisted clinical interviews (M-CIDI), conducted by clinically trained interviewers.

Results. 12-month prevalence for any DSM-IV study disorder is 31% (lifetime: 43%; 4-week: 20%) with anxiety disorders, mood disorders and somatoform syndromes being the most frequent diagnoses. Retrospective age of onset information reveals that most disorders begin early in life. Co-morbidity rates among mental disorders range from 44% to 94%. Correlates of increased rates of mental disorders and co-morbidity were: female gender (except for substance disorders), not being married, low social class, and poor somatic health status. Health care utilization for mental disorders depended on co-morbidity (30% in ‘pure’, 76% in highly co-morbid cases) and varied from 33% for substance use disorders to 75% for panic disorder.

Conclusions. Results confirm and extend results from other national studies using the same assessment instruments with regard to prevalence, co-morbidity and sociodemographic correlates, covering a broader range of DSM-IV disorders [i.e. somatoform disorders, all anxiety disorders (except PTSD), mental disorders due to substance or general medical factor, eating disorders]. Intervention rates were higher than in previous studies, yet still low overall.
Personality pathology and outcome in recurrently depressed women over 2 years of maintenance interpersonal psychotherapy
Authors: CYRANOWSKI J. M. , FRANK E. , WINTER E. , RUCCI P. , NOVICK D. , PILKONIS P. , FAGIOLINI A. , SWARTZ H. A. , HOUCK P. , KUPFER D. J.
Published: May 2005

Background. Empirical data on the impact of personality pathology on acute treatment outcome for depression are mixed, in part because of challenges posed by assessing trait-like personality patterns while patients are in an active mood episode. To our knowledge, no previous study has examined the effect of personality pathology on maintenance treatment outcome. By maintenance treatment we refer to long-term treatment provided to prevent depression recurrence among remitted patients.

Method. Structured Clinical Interviews for the DSM-III-R Personality Disorders (SCID-II) were obtained on a sample of 125 recurrently depressed women following sustained remission of the acute mood episode and prior to entering maintenance treatment. SCID-II interviews were then repeated following 1 and 2 years of maintenance interpersonal psychotherapy.

Results. At the pre-maintenance assessment, 21·6% of the sample met SCID-II personality disorder criteria. Co-morbid personality pathology was related to an earlier age of onset, more previous depressive episodes, and a greater need for adjunctive pharmacotherapy to achieve remission of the acute mood episode. Co-morbid personality pathology predicted both higher rates of depression recurrence and a shorter time to recurrence over the 2-year course of maintenance treatment. Notably, among those patients who remained depression-free, continuous levels of personality pathology steadily declined over the 2-year course of maintenance therapy.

Conclusions. Results highlight the need for early and effective intervention of both episodic mood disorder and inter-episode interpersonal dysfunction inherent to the personality disorders. Future maintenance treatment trials are needed to clarify the relationship between episodic mood disorder and personality function over time.
The cult of the equity for pension funds: should it get the boot?
Authors: SUTCLIFFE CHARLES
Published: May 2005

Over the last half century UK defined benefit pension schemes have followed the cult of the equity by investing a large proportion of their assets in equities. However, since the turn of the millennium this cult has faced two serious challenges – the halving of equity prices, and the complete rejection of equity investment by the Boots pension scheme in 2001. This paper summarises the history of the cult in the UK and the arguments advanced at the time to support its adoption. It then presents the case for the cult (excluding taxation, risk sharing and default insurance). This is followed by a detailed consideration of the validity of this case, including an examination of the relevant empirical evidence. It is concluded that, in the absence of taxation, risk sharing and default insurance, the asset allocation is indeterminate; and depends on the risk-return preferences adopted by the trustees.
Mind over matter:
Authors: Gaab Jens , Jucker Petra , Staub Franziska , Ehlert Ulrike
Published: May 2005

Zusammenfassung. Theoretischer Hintergrund: Neuere Befunde zeigen, dass psychobiologische Prozesse an der Entstehung emotionaler Prozesse beteiligt sind, wobei dysfunktionale Reaktionen neuroendokriner Systeme als mögliche biologische Korrelate psychischer Störungen diskutiert werden. Unklar ist, ob effektive psychotherapeutische Maßnahmen, wie z.B. Expositionstherapie bei Phobien, nicht nur auf Symptomebene, sondern auch physiologische Prozesse beeinflusst. Fragestellung: Hat eine erfolgreiche kognitiv-verhaltenstherapeutische Intervention (Wiederholte Exposition bei Spinnenängstlichen) Auswirkungen auf biologische Parameter und welche Rolle spielen dabei kognitive Prozesse? Methoden: Psychologischen (Bewertung, Angst) und biologischen Reaktionen (Cortisol und Herzrate) von fünfzehn Spinnenängstliche und fünfzehn gesunde Kontrollpersonen wurden während einer Spinnenexposition verglichen. Zusätzlich wurden bei Spinnenängstlichen Veränderungen dieser Parameter über den Verlauf von drei Expositionsterminen erfasst. Ergebnisse: Im Vergleich zu Kontrollpersonen zeigten Spinnenängstliche erhöhte biologische und emotionale Reaktion in der Exposition, welche sich im Verlauf der weiteren Expositionen normalisierten. Das Ausmaß dieser Veränderungen stand im Zusammenhang mit dem Ausmaß der Veränderungen der Bewertungsprozesse. Diskussion: Die Ergebnisse der Untersuchung zeigen, dass erfolgreiche Psychotherapie (auch) biologische Konsequenzen, im Sinne einer Normalisierung der kardiovaskulären und der endokrinen Stressreaktion, hat. Auf dem Hintergrund der physiologischen Bedeutung dieser Reaktionssysteme stellen diese physiologischen Effekte mögliche Voraussetzungen von Neulernen im Sinne einer neuronaler Reorganisation dar.
Der Einfluss von Models in der Werbung auf das Körperselbstbild der Betrachter/innen
Authors: Petersen Lars-Eric
Published: May 2005

Zusammenfassung. In der vorliegenden Studie wurde untersucht, ob die Betrachtung von Werbeinseraten mit Models das Körperselbstbild bei Frauen und Männern verändern kann. Den 124 weiblichen und männlichen Teilnehmern (Altersmittelwert: 30 Jahre; Range 18 bis 60 Jahre) der Studie wurden entweder Werbeinserate ohne Models (Kontrollgruppe), Werbeinserate mit weiblichen und männlichen Models (Experimentalgruppe 1) oder Werbeinserate mit Models ausschließlich des eigenen Geschlechts (Experimentalgruppe 2) präsentiert. Die Ergebnisse der Untersuchung zeigen unter anderem, dass weibliche Teilnehmer beider Experimentalgruppen eine größere Diskrepanz zwischen ihrem realen und idealen Körperschema wahrnehmen und auch stärker davon ausgehen, dass andere Frauen ein dünneres Ideal anstreben als Frauen der Kontrollgruppe. Bei männlichen Teilnehmern konnten dagegen keine bedeutsamen Unterschiede in der Körperwahrnehmung zwischen Männern der Experimentalgruppen und der Kontrollgruppe festgestellt werden. Diese Ergebnisse werden in Bezug auf zum Teil konträre Ergebnisse einer aktuellen amerikanischen Studie und hinsichtlich ihrer gesellschaftlichen Relevanz diskutiert.
Determinanten der Rücklaufquote in Online-Panels
Authors: Batinic Bernad , Moser Klaus
Published: May 2005

Zusammenfassung. Überprüft wird der Einfluss der Gratifikationsform (Bonuspunkte, Verlosungen, Ergebnisberichte), des Untersuchungszwecks (wissenschaftliche versus kommerzielle Befragung) und der Zahl der Reminder auf die Rücklaufquote in Online-Panels. Hierzu wurden 68 Online-Umfragen, die in vier Online-Panels in den Jahren 2000 bis 2004 durchgeführt wurden, miteinander verglichen. Die durchschnittliche Rücklaufquote über alle untersuchten Online-Panel Umfragen hinweg betrug 71,9 Prozent (N = 57.598) bzw. stichprobengewichtet 73,5 Prozent. Vergabe von Bonuspunkten und Zahl der Reminder stehen in einem positiven Zusammenhang zur Rücklaufquote. Zwischen der Untersuchungsthematik (Forschung vs. kommerzielles Ziel) und der Rücklaufquote konnte hingegen nur ein schwacher Zusammenhang festgestellt werden. Die Ankündigung eines Ergebnisberichts über die Befragung steht entgegen den Erwartungen in einem negativen Zusammenhang zur Rücklaufquote. Generalisierbarkeit der Befunde sowie weitere Forschungsfragen werden abschließend diskutiert.
The Atlantic freshwater budget as a diagnostic for the existence of a stable shut down of the meridional overturning circulation
Authors: de Vries Pedro , Weber Susanne L.
Published: May 2005

Which physical processes effectively determine the stability regime of the Atlantic meridional overturning circulation (MOC) is not yet fully understood. We investigate the role of the oceanic freshwater transport into the basin, employing a coupled model of intermediate complexity. By modifying the longitudinal variation of surface salinities near the southern border at 33°S, the amount of salt flowing out of the Atlantic via the Brazil Current can be regulated. In turn, this will influence whether the MOC exports or imports salt water. The latter is associated with a basin‐scale salinity‐overturning feedback, which can be either positive or negative. Pulse experiments strongly suggest that its sign determines the existence of a monostable or bistable regime in our model.
Lehmann discontinuity beneath North America: No role for seismic anisotropy
Authors: Vinnik L. , Kurnik E. , Farra V.
Published: May 2005

The Lehmann discontinuity in the upper mantle is often interpreted as a boundary separating anisotropic and isotropic media. We demonstrate, however, that seismic anisotropy plays, if any, a minor role in the origin of the Lehmann discontinuity. Our data are obtained with S receiver function technique from recordings of the MOMA seismograph array in the eastern USA. Part of the data is processed with a new modification of this technique. We observe Sp phase converted from the Lehmann discontinuity at a depth around 200 km with comparable amplitudes and similar polarities in two azimuths differing by about 90°. Contrary to the observations, the polarity in the synthetic seismograms for models with azimuthal anisotropy is opposite for the azimuths differing by 90°. Radial anisotropy with a slow vertical direction results in the Sp phase with the polarity opposite to the observed one.
Modeled and observed clouds during Surface Heat Budget of the Arctic Ocean (SHEBA)
Authors: Wyser Klaus , Jones Colin G.
Published: May 2005

Observed monthly mean cloud cover from the SHEBA site is found to differ by a substantial amount during winter depending on cloud observing instrument. This makes it difficult for climate modelers to evaluate modeled clouds and improve parameterizations. Many instruments and human observers cannot properly detect the thinnest clouds and count them as clear sky instead, resulting in too low cloud cover. To study the impact from the difficulties in the detection of thin clouds, we compute cloud cover in our model with a filter that removes the thinnest clouds. Optical thickness is used as a proxy to identify thin clouds as we are mainly interested in the impact of clouds on radiation. With the results from a regional climate model simulation of the Arctic, we can reproduce the large variability in wintertime cloud cover between instruments when assuming different cloud detection thresholds. During winter a large fraction of all clouds are optically thin, which causes the large sensitivity to filtering by optical thickness. During summer, most clouds are far above the optical thickness threshold and filtering has no effect. A fair comparison between observed and modeled cloud cover should account for thin clouds that may be present in models but absent in the observational data set. Difficulties with the proper identification of clouds and clear sky also has an effect on cloud radiative forcing. The derived clear‐sky longwave flux at the surface can vary by some W m−2 depending on the lower limit for the optical thickness of clouds. This impacts on the “observed” LW cloud radiative forcing and suggests great care is needed in using satellite‐derived cloud radiative forcing for model development.
Observations of smoke‐influenced aerosol during the Yosemite Aerosol Characterization Study: Size distributions and chemical composition
Authors: McMeeking G. R. , Kreidenweis S. M. , Carrico C. M. , Lee T. , Collett J. L. , Malm W. C.
Published: May 2005

The Yosemite Aerosol Characterization Study (YACS) took place in Yosemite National Park from 15 July to 5 September 2002, during which time air masses arriving at the site were believed to have been influenced by smoke from numerous wildfires active in the western United States. Physical, optical, and chemical aerosol measurements were made to characterize visibility and to help define aerosol sources contributing to haze in the park, with a particular emphasis on the role of prescribed and wild fires. Measurements of dry aerosol size distributions were made with a differential mobility analyzer (DMA) and an optical particle counter (OPC). An iterative alignment method assuming a range of refractive indices was applied to OPC size distributions to match them to DMA size distributions, returning the real refractive index that yielded the best fit and generating a complete size distribution for 0.04 < Dp < 2 μm. Retrieved dry aerosol real refractive indices generally ranged from 1.56 to 1.59 and were comparable to values estimated from composition measurements. Organic carbon was the dominant aerosol species during the study, particularly during periods identified as smoke impacted. Mie theory was used to determine mass scattering efficiencies (λ = 530 nm) from measured dry size distributions using retrieved refractive indices. These ranged from 3 to 6 m2 g−1, with the highest values occurring during smoke‐impacted episodes.
Satellite and radar analysis of the volcanic‐cumulonimbi at Mount Pinatubo, Philippines, 1991
Authors: Tupper Andrew , Oswalt J. Scott , Rosenfeld Daniel
Published: May 2005

Several observers reported interesting convective phenomena in the months and years following the 15 June 1991 climactic eruption of Mount Pinatubo, Philippines. The observed phenomena included deep convection resulting from (1) lower level eruptions, (2) secondary phreatic explosions, and (3) enhanced surface heating. We have compared radar records and satellite imagery to obtain a more coherent understanding of these “volcanic‐cumulonimbi” from 17 June to 30 September 1991 and to identify observational challenges for future events. Geostationary satellite imagery analysis for the period shows that the dominant localized effect on convection following the eruption was to bring the afternoon/evening peak in the diurnal convective cycle over the mountain forward by 2–3 hours. We examined four cases in detail and identified a number of possible interactions between the volcano and the meteorological environment. For three of these cases, the volcanic emissions apparently mixed with cumulonimbi developing around the volcano; on 21 June 1991, microphysical analyses clearly show a strong reduction in cloud top effective particle radius caused by the additional aerosols in the cloud, while on the two other occasions, there was a slight or barely detectible reduction. In the fourth case, for a cumulonimbus developing above a major secondary phreatic explosion, no unusually small cloud top effective radii were found, perhaps because the ash injected into the cloud was dominated by giant cloud condensation nuclei. These cases verify that volcanic emissions can be released through the depth of the troposphere and lower stratosphere from relatively small eruptions. Future major tropical eruptions and their aftermaths should be studied using intensive ground‐ and satellite‐based observations to explore these phenomena further.
Twilight sky brightness measurements as a useful tool for stratospheric aerosol investigations
Authors: Mateshvili Nina , Fussen Didier , Vanhellemont Filip , Bingen Christine , Kyrölä Erkki , Mateshvili Iuri , Mateshvili Giuli
Published: May 2005

In this paper we demonstrate how twilight sky brightness measurements can be used to obtain information about stratospheric aerosols. Beside this, the measurements of the distribution and the variability of the twilight sky brightness may help to understand how the stratospheric aerosols affect the radiation field, which is important for correct calculations of photodissociation rates. Multispectral measurements of twilight sky brightness were carried out in Abastumani Observatory (41.8°N, 42.8°E), Georgia, South Caucasus, during the period (1991–1993) when the level of stratospheric aerosols was substantially enhanced after the 1991 Mount Pinatubo eruption. The twilight sky brightness was measured at 9 wavelengths (422, 474, 496, 542, 610, 642, 678, 713, and 820 nm) for solar zenith angles from 89° to 107°. There are clear indications of a growth of the stratospheric aerosol layer after the eruption of Mount Pinatubo that manifests itself by “humps” in twilight sky brightness dependences versus solar zenith angle. Similar features were obtained using a radiative transfer code constrained by the SAGE II aerosol optical thicknesses. It is shown how an enhancement of stratospheric aerosol loading perturbs the twilight sky brightness due to light scattering and absorption in the aerosol layer. The influence of ozone variations and background stratospheric aerosols on twilight sky brightness has also been analyzed. The optical thicknesses of the stratospheric aerosol layer obtained from the twilight measurements of 1990–1993 show a good agreement with SAGE II results. The spectral variations of the stratospheric aerosol extinction for pre‐Pinatubo and post‐Pinatubo measurements reflect the aerosol growth after the eruption. Finally, the utilization of twilight sky brightness measurements for validation of satellite‐based measurements of the stratospheric aerosol is proposed.
Effects of modifications to the Zhang‐McFarlane convection parameterization on the simulation of the tropical precipitation in the National Center for Atmospheric Research Community Climate Model, version 3
Authors: Zhang Guang J. , Mu Mingquan
Published: May 2005

This study compares the simulation of tropical convection in the National Center for Atmospheric Research Community Climate Model, version 3 (CCM3), using the original and a revised convective parameterization closure in the Zhang‐McFarlane scheme. The revised closure couples convection to the large‐scale forcing in the free troposphere instead of to the convective available potential energy in the atmosphere as employed in the original closure. In addition, a relative humidity threshold is used for convection trigger. It is shown that the mean precipitation distribution in the tropical regions for both summer and winter is, in general, improved when the new closure is used. During June, July, and August the precipitation in the western Pacific monsoon region is significantly enhanced, alleviating the negative precipitation bias there in the model. The spurious precipitation in the Arabian Peninsula desert is completely eliminated. During December, January, and February the South Pacific Convergence Zone is enhanced considerably. All these changes are desirable in addressing important model deficiencies. The probability distributions of the precipitation intensity from the model simulations are compared with that from the Tropical Rainfall Measurement Mission (TRMM) data. It is shown that over 90% of the CCM3 precipitation is from light rain with rainfall rate less than 1 mm h−1, whereas the simulation with the new closure and the TRMM observations show significant contribution (30–40%) from rainfall rates greater than 2 mm h−1. Precipitation simulation over the western North Pacific summer monsoon region and the Arabian Peninsula was examined in detail to understand the causes of the precipitation biases in CCM3 over these regions. It is demonstrated that the convective available potential energy (CAPE)‐based closure limits the CAPE buildup at the beginning of the monsoon season, resulting in the under simulation of the western North Pacific monsoon precipitation. In the Arabian Peninsula the positive feedback between convection and surface evaporation leads to the spurious heavy precipitation center there. In addition to the new closure the use of relative humidity threshold is also found to be important to the improvement of the simulation.
Late Cretaceous‐Tertiary tectonics of the southwest Pacific: Insights from U‐Pb sensitive, high‐resolution ion microprobe (SHRIMP) dating of eclogite facies rocks from New Caledonia
Authors: Spandler Carl , Rubatto Daniela , Hermann Jörg
Published: May 2005

We present new U‐Pb sensitive, high‐resolution ion microprobe (SHRIMP) dates for zircon from eclogite facies samples from northern New Caledonia, which have important consequences for the Late Cretaceous to Eocene tectonic evolution of the southwest Pacific region. Two high‐pressure metapelites contain zoned zircon crystals. Cores of these crystals represent inherited magmatic zircon grains, which yield an age of 85 Ma in both samples. Igneous zircon domains from a metamorphosed mafic cumulate and a felsic metasedimentary rock were also dated at 55 Ma. The igneous zircon of uniform age in rocks of sedimentary origin indicates that sedimentation took place from a restricted source area soon after magmatism. Therefore the protoliths of the eclogite facies rocks are considered to have formed between 85 and 55 Ma in a back‐arc basin. This time period matches the age of the unmetamorphosed Poya Terrane of western New Caledonia and provides further evidence for a direct link between the two terranes. In the metapelites, irregular zircon rims that cross cut the oscillatory zoning of the cores have low trace element and Th/U contents and contain inclusions of high‐pressure minerals providing evidence that these zircon rims formed during eclogite facies metamorphism. Therefore the 44.1 ± 0.9 Ma and 44.5 ± 1.2 Ma ages obtained from these rims represent burial related to subduction of the back‐arc basin. It is suggested that subduction initiated soon after deposition of the youngest sediments at 55 Ma and stopped at 44 Ma during attempted subduction of continental crust, now represented as the Norfolk Ridge. Therefore the subduction system that produced the high‐pressure rocks could only have operated for a maximum of 11 m.y. and would have been relatively hot. The 44 Ma age constraint for peak metamorphism also significantly predates (by 10 m.y.) the timing of obduction of the New Caledonia Ultramafic Nappe, discounting any link between obduction and high‐pressure metamorphism. Combining our results with previously documented geological data, we present a revised model for the geological development of New Caledonia, which involves multiple episodes of compression and extension during the Eocene.
A three‐dimensional model of microbial transport and biodegradation at the Schoolcraft, Michigan, site
Authors: Phanikumar M. S. , Hyndman David W. , Zhao Xianda , Dybas Michael J.
Published: May 2005

Bioremediation can be a cost‐effective approach to clean up groundwater contaminants, especially in cases where numerical models have been used to evaluate microbial processes and design remediation strategies. This paper describes the three‐dimensional reactive transport modeling of carbon tetrachloride (CT) bioremediation at the Schoolcraft site in western Michigan. A “biocurtain” was created to remediate this site using a recirculation well gallery installed normal to groundwater flow, which was inoculated with nonnative microbes and fed with weekly additions of electron donor (acetate) and nutrients. The model simulates the transport and reactions of aqueous and sorbed phase CT, acetate, electron acceptor (nitrate), mobile and immobile microbes, and tracer (bromide). Simulated microbial processes include growth, decay, attachment, detachment, and endogenous respiration. This model was used to predict solute concentrations across the site using laboratory‐based reaction parameters and to evaluate changes in rates from the laboratory to the field. A reasonable agreement was found between predicted and observed acetate and nitrate concentrations; however, a lower CT degradation rate was needed to describe the CT concentrations observed after the inoculation event.
Solving the paradox of the end of the Little Ice Age in the Alps
Authors: Vincent Christian , Le Meur Emmanuel , Six Delphine , Funk Martin
Published: May 2005

The causes and timing of the Little Ice Age (fifteenth to nineteenth centuries) are still unclear (Crowley, 2000; Bond et al., 2001; Shindell et al., 2001). During the last part of this event (1760–1830), the advance of glaciers in the Alps conflicts with the summer temperature signal (Intergovernmental Panel on Climate Change, 2001). This paper attempts to solve this paradox. From glacier fluctuations and monthly temperature data, we show that mean winter precipitation was higher by at least 25% during this final phase compared to the twentieth century average and that glacier recession after 1830 clearly resulted from a winter precipitation decrease and not a temperature increase. Conversely, since the beginning of the twentieth century, glacier changes have been driven mainly by temperature change.
Arginine methylation regulates IL-2 gene expression: a role for protein arginine methyltransferase 5 (PRMT5)
Authors: RICHARD Stéphane , MOREL Mélanie , CLÉROUX Patrick
Published: May 2005

Arginine methylation is a post-translational modification resulting in the generation of aDMAs (asymmetrical ω-NG, NG-dimethylated arginines) and sDMAs (symmetrical ω-NG, N′G-dimethylated arginines). The role of arginine methylation in cell signalling and gene expression in T lymphocytes is not understood. In the present study, we report a role for protein arginine methylation in regulating IL-2 (interleukin 2) gene expression in T lymphocytes. Leukaemic Jurkat T-cells treated with a known methylase inhibitor, 5′-methylthioadenosine, had decreased cytokine gene expression, as measured using an NF-AT (nuclear factor of activated T-cells)-responsive promoter linked to the luciferase reporter gene. Since methylase inhibitors block all methylation events, we performed RNA interference with small interfering RNAs against the major PRMT (protein arginine methyltransferases) that generates sDMA (PRMT5). The dose-dependent decrease in PRMT5 expression resulted in the inhibition of both IL-2- and NF-AT-driven promoter activities and IL-2 secretion. By using an sDMA-specific antibody, we observed that sDMA-containing proteins are directly associated with the IL-2 promoter after T-cell activation. Since changes in protein arginine methylation were not observed after T-cell activation in Jurkat and human peripheral blood lymphocytes, our results demonstrate that it is the recruitment of methylarginine-specific protein(s) to cytokine promoter regions that regulates their gene expression.
Interferon-γ-dependent tyrosine phosphorylation of MEKK4 via Pyk2 is regulated by annexin II and SHP2 in keratinocytes
Authors: HALFTER Ursula M. , DERBYSHIRE Zachary E. , VAILLANCOURT Richard R.
Published: May 2005

IFNγ (interferon-γ) binding to its cognate receptor results, through JAK (Janus kinase), in direct activation of receptor-bound STAT1 (signal transducer and activator of transcription 1), although there is evidence for additional activation of a MAPK (mitogen-activated protein kinase) pathway. In the present paper, we report IFNγ-dependent activation of the MEKK4 (MAPK/extracellular-signal-regulated kinase kinase kinase 4) pathway in HaCaT human keratinocytes. MEKK4 is tyrosine­-phosphorylated and the IFNγ-dependent phosphorylation requires intracellular calcium. Calcium-dependent phosphorylation of MEKK4 is mediated by Pyk2. Moreover, MEKK4 and Pyk2 co-localize in an IFNγ-dependent manner in the perinuclear region. Furthermore, the calcium-binding protein, annexin II, and the calcium-regulated kinase, Pyk2, co-immunoprecipitate with MEKK4 after treatment with IFNγ. Immunofluorescence imaging of HaCaT cells shows an IFNγ-dependent co-localization of annexin II with Pyk2 in the perinuclear region, suggesting that annexin II mediates the calcium-dependent regulation of Pyk2. Tyrosine phosphorylation of MEKK4 correlates with its activity to phosphorylate MKK6 (MAPK kinase 6) in vitro and subsequent p38 MAPK activation in an IFNγ-dependent manner. Additional studies demonstrate that the SH2 (Src homology 2)-domain-containing tyrosine phosphatase SHP2 co-immunoprecipitates with MEKK4 in an IFNγ-dependent manner and co-localizes with MEKK4 after IFNγ stimulation in the perinuclear region in HaCaT cells. Furthermore, we provide evidence that SHP2 dephosphorylates MEKK4 and Pyk2, terminating the MEKK4-dependent branch of the IFNγ signalling pathway.
Internalization and trafficking of guanylyl (guanylate) cyclase/natriuretic peptide receptor A is regulated by an acidic tyrosine-based cytoplasmic motif GDAY
Authors: PANDEY Kailash N. , NGUYEN Huong T. , GARG Renu , KHURANA Madan L. , FINK Jude
Published: May 2005

We have identified a GDAY motif in the C-terminal domain of guanylyl cyclase (guanylate cyclase)/NPRA (natriuretic peptide receptor A) sequence, which serves a dual role as an internalization signal and a recycling signal. To delineate the role of the GDAY motif in receptor internalization and sequestration, we mutated Gly920, Asp921 and Tyr923 to alanine residues (GDAY/AAAA) in the NPRA cDNA sequence. The cDNAs encoding wild-type and mutant receptors were transfected in HEK-293 cells (human embryonic kidney 293 cells). The internalization studies of ligand–receptor complexes revealed that endocytosis of 125I-ANP by HEK-293 cells expressing G920A, Y923A or GDAY/AAAA mutant receptor was decreased by almost 50% (P<0.001) when compared with cells expressing the wild-type receptor. However, the effect of D921A mutation on receptor internalization was minimal. Ligand-mediated down-regulation of G920A, Y923A and GDAY/AAAA mutant receptors was decreased by 35–40% when compared with wild-type NPRA. Subsequently, the recycling of internalized D921A and GDAY/AAAA mutant receptors from the intracellular pool was decreased by more than 40±4% when compared with wild-type NPRA. Recycling of G920A and Y923A mutant receptors was also decreased, but to a significantly lesser extent compared with the D921A or GDAY/AAAA mutant receptors. We conclude that the Gly920 and Tyr923 residues within the GDAY consensus motif are necessary for internalization, and that residue Asp921 is important for recycling of NPRA. The current results provide new evidence for a dual role of the GDAY sequence motif in ligand-mediated internalization, recycling and down-regulation of a single-transmembrane receptor protein NPRA.
Separation of native prion protein (PrP) glycoforms by copper-binding using immobilized metal affinity chromatography (IMAC)
Authors: MÜLLER Henrik , STROM Alexander , HUNSMANN Gerhard , STUKE Andreas W.
Published: May 2005

The conformational conversion of the normal cellular prion protein (PrPC) into the pathology-associated PrPSc isoform is a key event in TSEs (transmissible spongiform encephalopathies). The host PrPC molecule contains two N-linked glycosylation sites and binds copper under physiological conditions. In contrast with PrPC, PrPSc is insoluble in non-ionic detergents and does not bind to Cu2+ ions. Hence, we utilized copper binding to separate and characterize both PrP isoforms. Infected and uninfected murine brain and bovine stem brain specimens were treated with the mild non-ionic detergent n-octyl-β-D-glucopyranoside (octylglucoside) to maintain the native PrP conformations during isolation. The solubilized homogenates were loaded on to Cu2+-saturated IMAC (immobilized metal affinity chromatography) columns and eluted using the chelating agent EDTA. Fractions were separated by SDS/PAGE and analysed by immunoblotting using anti-PrP monoclonal antibodies for glycosylation profiling. Whereas native PrPC and denatured PrPSc were retained by a Cu2+-loaded resin, native PrPSc and PrPres [PK (proteinase K)-resistant PrP] passed through the column. We demonstrate here that the IMAC technique is appropriate to isolate and partially purify PrPC from healthy brains in its native-like and biologically relevant glycosylated copper-binding forms. The IMAC technique is also well suited for the separation of native PrPC from aggregated PrPSc in infected brains. Our results indicate that in contrast with PrPSc in uninfected as well as infected brains, PrPC is predominantly present in the glycosylated forms.
Evidence against reciprocal regulation of Ca2+ entry by vasopressin in A7r5 rat aortic smooth-muscle cells
Authors: BRUEGGEMANN Lioubov I. , MARKUN Daniel R. , BARAKAT John A. , CHEN Haiyan , BYRON Kenneth L.
Published: May 2005

Recent studies by Moneer and Taylor [(2002) Biochem. J. 362, 13–21] have proposed a reciprocal regulation of two Ca2+-entry pathways by AVP ([Arg8]-vasopressin) in A7r5 vascular smooth-amuscle cells. Their model proposes that AVP inhibits CCE (capacitative Ca2+ entry) and predicts a rebound of CCE after the removal of AVP. In the present study, we used whole-cell perforated patch-clamp techniques to measure ISOC (store-operated current) corresponding to CCE in A7r5 cells. When 100 nM AVP is present, it activates ISOC with no apparent rebound on removal of AVP. ISOC activated by thapsigargin or cyclopiazonic acid was not inhibited by 100 nM AVP. We also used fura 2 fluorescence techniques to re-examine the model of Moneer and Taylor, specifically focusing on the proposed inhibition of CCE by AVP. We find that 100 nM AVP activates capacitative Mn2+ entry and does not inhibit thapsigargin- or cyclopiazonic acid-activated Mn2+ entry. Moreover, Ca2+ entry after depletion of intracellular Ca2+ stores is enhanced by AVP and we detect no rebound of Ca2+ or Mn2+ entry after AVP removal. On the basis of these findings, we conclude that AVP does not inhibit CCE in A7r5 cells.
Subcellular distribution of GABAB receptor homo- and hetero-dimers
Authors: VILLEMURE Josée-France , ADAM Lynda , BEVAN Nicola J. , GEARING Katy , CHÉNIER Sébastien , BOUVIER Michel
Published: May 2005

GBRs (GABAB receptors; where GABA stands for γ-aminobutyric acid) are G-protein-coupled receptors that mediate slow synaptic inhibition in the brain and spinal cord. In vitro assays have previously demonstrated that these receptors are heterodimers assembled from two homologous subunits, GBR1 and GBR2, neither of which is capable of producing functional GBR on their own. We have used co-immunoprecipitation in combination with bioluminescence and fluorescence resonance energy transfer approaches in living cells to assess directly the interaction between GBR subunits and determine their subcellular localization. The results show that, in addition to forming heterodimers, GBR1 and GBR2 can associate as stable homodimers. Confocal microscopy indicates that, while GBR1/GBR1 homodimers are retained in the endoplasmic reticulum and endoplasmic reticulum–Golgi intermediate compartment, both GBR2/GBR2 homodimers and GBR1/GBR2 heterodimers are present at the plasma membrane. Although these observations shed new light on the assembly of GBR complexes, they raise questions about the potential functional roles of GBR1 and GBR2 homodimers.
Regulatory sequence responsible for insulin destabilization of cytochrome P450 2B1 (CYP2B1) mRNA
Authors: TRUONG Nhu-Traï , MONCION Arlette , BAROUKI Robert , BEAUNE Philippe , de WAZIERS Isabelle
Published: May 2005

Diabetes has been reported to increase CYP2E1 (cytochrome P450) and CYP2B1 expression at both the mRNA and protein levels in rat livers. This increase has been attributed to mRNA stabilization and can be reversed by daily insulin treatment. In a previous study, we showed that this hormone directly down-regulates CYP2E1 and 2B1 expression through a post-transcriptional mechanism in rat hepatoma cell lines. We then aimed to identify the molecular mechanisms involved in this regulation. We first identified a 16-mer sequence that we later showed to be the actual functional target of insulin on the rat CYP2E1 mRNA. Similar work was performed with CYP2B1. We first investigated the presence of mRNA–protein interactions. Using cytoplasmic proteins of Fao cells treated or not with insulin (0.1 μM) and the full-length CYP2B1 mRNA as a probe, a major CYP2B1 RNA–protein complex was observed with RNase T1 protection experiments. With the use of different CYP2B1 mRNA probes and by means of competition experiments with antisense oligonucleotides, a protein fixation site was located on a 16-nt sequence in the 5′ part of the coding region. This sequence has a hairpin loop structure, shows 80% sequence identity with a structure previously identified on CYP2E1 and is also responsible for the post-transcriptional effects of insulin on this mRNA. Protein(s) bound to both CYP2B1 and CYP2E1 sequences are cytosolic and have an apparent molecular mass of 60 kDa. The protein(s) that bind(s) to both these sequences and the insulin transduction signal involved in this regulation remain(s) to identified.
Role of cis-acting elements in the control of SERCA2b Ca2+ pump mRNA decay by nuclear proteins
Authors: MISQUITTA Christine M. , GHOSH Paromita , MWANJEWE James , GROVER Ashok K.
Published: May 2005

Alternative splicing at position 3495 b yields SERCA2 (sarco/endoplasmic reticulum Ca2+ pump 2) RNA species, namely SERCA2a and SERCA2b which differ in 3′-end regions. This results in SERCA2b RNA being less stable. In vitro decay experiments show that, in the presence of protein extracts from nuclei of LVMs (left ventricular myocytes), the rate of decay of both SERCA2b RNA and synthetic RNA from its 3′-region is greater than that of the corresponding SERCA2a RNA. To search for cis-acting instability elements in the 3′-region of SERCA2b, we examined the effects of LVM nuclear protein extracts on the in vitro decay of six short overlapping capped [m7G(5′)ppp(5′)Gm] and polyadenylated (A40) RNA fragments from the 3′-end region (3444–4472) of SERCA2b. The proximal fragment 2B1 (3444–3753) was the most unstable. 2B1 RNA without a cap or a polyadenylated tail was analysed further in electrophoretic mobility-shift assays, and was observed to bind to protein(s) in the nuclear extracts. Based on competition for binding to nuclear proteins between radiolabelled 2B1 RNA and short unlabelled RNA fragments, the cis-acting element involved in this binding was the sequence 2B1-4. 2B1-4 is a 35-base (3521–3555, CCAGUCCUGCUCGUUGUGGGCGUGCACCGAGGGGG) GC-rich region just past the splice site (3495). Nuclear extracts decreased the electrophoretic mobility of the radiolabelled 2B1-4 RNA which bound to two proteins (19 and 21 kDa) in cross-linking experiments. Excess 2B1-4 RNA decreased the decay of the 2B1 RNA by the nuclear protein extract. 2B1-del 4 RNA (2B1 with the 2B1-4 domain deleted) also decayed more slowly than the control 2B1 RNA. Thus SERCA2b contains a novel GC-rich cis-acting element involved in its decay by nuclear proteins.
N-linked oligosaccharides are required to produce and stabilize the active form of chondroitin 4-sulphotransferase-1
Authors: YUSA Akiko , KITAJIMA Ken , HABUCHI Osami
Published: May 2005

C4ST-1 (chondroitin 4-sulphotransferase-1) transfers sulphate to position 4 of N-acetylgalactosamine in chondroitin. We showed previously that purified C4ST-1 from the culture medium of rat chondrosarcoma cells was a glycoprotein containing approx. 35% N-linked oligosaccharides. In the present paper, we investigated the functional role of the N-linked oligosaccharides attached to C4ST-1. We found that (i) treatment of recombinant C4ST-1 with peptide N-glycosidase F caused a marked decrease in activity, (ii) production of the active form of C4ST-1 by COS-7 cells transfected with cDNA of C4ST-1 was inhibited by tunicamycin, (iii) deletion of the N-glycosylation site located at the C-terminal region of C4ST-1 abolished activity, (iv) attachment of a single N-glycan at the C-terminal region supported production of the active form of C4ST-1, but the resulting recombinant enzyme was much more unstable at 37 °C than the control recombinant protein, and (v) truncation of C-terminal region up to the N-glycosylation site at the C-terminal region resulted in total loss of activity. These observations strongly suggest that N-linked oligosaccharides attached to C4ST-1 contribute to the production and stability of the active form of C4ST-1. In addition, the N-linked oligosaccharide at the C-terminal region appears to affect the glycosylation pattern of recombinant C4ST; a broad protein band of the wildtype protein resulting from microheterogeneity of N-linked oligosaccharides disappeared and four discrete protein bands with different numbers of N-linked oligosaccharides appeared when the N-linked oligosaccharide at the C-terminal region was deleted.
A new class of glutathione S-transferase from the hepatopancreas of the red sea breamPagrus major
Authors: KONISHI Takafumi , KATO Keitaro , ARAKI Toshiyoshi , SHIRAKI Kentaro , TAKAGI Masahiro , TAMARU Yutaka
Published: May 2005

To elucidate drug deposition and metabolism in cultured marine fishes, in a previous study we isolated and purified the GSTs (glutathione S-transferases) from the hepatopancreas of the red sea bream Pagrus major that contained 25 and 28 kDa GST subunits. The 25 kDa GST subunits encoded by two genes (GSTA1 and GSTA2) have been identified as Alpha-class GSTs. In the present study, we performed the molecular cloning and characterization of the GSTR1 gene encoding the 28 kDa GST subunit from the Pa. major hepatopancreas. The nucleotide sequence of GSTR1 was composed of an ORF (open reading frame) of 675 bp encoding a protein of 225 residues with a predicted molecular mass of 25.925 Da. A search of the BLAST protein database revealed that the deduced amino acid sequence of GSTR1 was structurally similar to that of GSTs derived from other fishes such as largemouth bass (Micropterus salmoides) and plaice (Pleuronectes platessa). The genomic DNA containing the GSTR1 gene was found to consist of six exons and five introns quite distinct from mammalian Theta-class GSTs. We have purified and characterized the recombinant GSTR1 enzyme (pmGSTR1-1) which showed activity only towards 1-chloro-2,4-dinitrobenzene, although it had no detectable activity towards cumene hydroperoxide, 1,2-dichloro-4-nitrobenzene, ethacrynic acid, 4-hydroxynonenal and p-nitrobenzyl chloride. Moreover, pmGSTR1-1 revealed remarkable heat instability (melting temperature Tm=30.3±0.11 °C). Collectively, our results indicated that the characteristic GST genes including GSTR1 have been conserved and functional in fishes. Therefore we designate them ‘Rho-class’, a new class of GSTs.
An unusual fold for potassium channel blockers: NMR structure of three toxins from the scorpion Opisthacanthus madagascariensis
Authors: CHAGOT Benjamin , PIMENTEL Cyril , DAI Li , PIL Joost , TYTGAT Jan , NAKAJIMA Terumi , CORZO Gerardo , DARBON Hervé , FERRAT Gilles
Published: May 2005

The Om-toxins are short peptides (23–27 amino acids) purified from the venom of the scorpion Opisthacanthus madagascariensis. Their pharmacological targets are thought to be potassium channels. Like Csα/β (cystine-stabilized α/β) toxins, the Om-toxins alter the electrophysiological properties of these channels; however, they do not share any sequence similarity with other scorpion toxins. We herein demonstrate by electrophysiological experiments that Om-toxins decrease the amplitude of the K+ current of the rat channels Kv1.1 and Kv1.2, as well as human Kv1.3. We also determine the solution structure of three of the toxins by use of two-dimensional proton NMR techniques followed by distance geometry and molecular dynamics. The structures of these three peptides display an uncommon fold for ion-channel blockers, Csα/α (cystine-stabilized α-helix–loop–helix), i.e. two α-helices connected by a loop and stabilized by two disulphide bridges. We compare the structures obtained and the dipole moments resulting from the electrostatic anisotropy of these peptides with those of the only other toxin known to share the same fold, namely κ-hefutoxin1.