bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Trends in Contingent Work Research
Authors: Connelly Catherine E. , Gallagher Daniel G.
Published: July 2004

In the past decade there has been growing internationally-based evidence towards a trend in organizational staffing strategies which have placed emphasis upon the direct or brokered hiring of workers on temporary, fixed-term or “contingent” employment contracts in lieu of contracts with the implication of an ongoing relationship. Concurrently, there has been an emergence of research activity concerning individual and organizational-level consequences associated with the increased organizational reliance on fixed-term contracts in the workplace. This paper provides an overview of the contingent work literature and identifies topical themes and research questions which have been the primary focus of attention, as well as the possible causal interrelationships among the diverse constructs which have been examined. The paper highlights aspects of the existing research that may benefit from further exploration, as well as consideration of a number of theoretical and methodological issues which have also emerged. © 2004Elsevier Inc. All rights reserved.
Mediengewalt, Lebenswelt und Persönlichkeit - eine Problemgruppenanalyse bei Jugendlichen
Authors: Hopf Werner H.
Published: July 2004

Zusammenfassung. Eine Querschnittsstudie untersucht zentrale Einflüsse auf Aggressivität, Gewaltbereitschaft/Friedfertigkeit in der Problemgruppe der Schüler/innen der Klassen 5 bis 10 in Hauptschulen. Erfasst wurden Variablen aus den Bereichen Mediengewaltkonsum, sozialer Kontext, Persönlichkeit sowie emotionale Reaktionen bei realer und fiktionaler Gewalt. Als zusätzlicher Aspekt wurde der Einfluss eines niedrigen Familieneinkommens (Armut) berücksichtigt. Die Analyse der Daten basierte auf dem General Aggression Model von Anderson und Bushman. Einflüsse, die Aggression erhöhen, konnten in 7 Hauptfaktoren zusammengefasst werden: (1) Häufigkeit des Mediengewaltkonsums, (2) aggressive Emotionen beim Mediengewaltkonsum, (3) gewaltorientierte Überzeugungen, (4) Hass, Wut und Rache bei Gruppengewalt, (5) hoher TV-Konsum der Eltern, (6) Hass, Wut und Rache bei elterlicher Gewalt, (7) materialistische Wertorientierungen. Extremgruppenvergleiche und Pfadanalysen bestätigten die Bedeutung des Mediengewaltkonsums und der durch Gewalt bedingten Emotionen für die Entstehung von Aggressivität. Friedfertigkeit hing ab von familialer Kommunikation, Medienerziehung und sozialen Kompetenzen.
Remotely sensed seasonal dynamics of phytoplankton in the Ligurian Sea in 1997–1999
Authors: Nezlin Nikolay P. , Lacroix Genevieve , Kostianoy Andrey G. , Djenidi Salim
Published: July 2004

Remotely sensed data and a one‐dimensional hydrophysical model were used to study the seasonal dynamics of surface plant pigments concentration in the Ligurian‐Provençal basin. The variations of phytoplankton biomass were estimated from the observations of the Coastal Zone Color Scanner (1978–1986) and Sea‐viewing Wide Field‐of‐view Sensor (SeaWiFS) (September 1997 to October 1999) radiometers. The factors of physical environment analyzed included remotely sensed sea surface temperature (from advanced very high resolution radiometers), wind, air temperature, and atmospheric precipitation. The Geohydrodynamics and Environment Research (GHER) model was used to explain the observed correlations between the physical forcing and the response of phytoplankton biomass. The general pattern of phytoplankton seasonal dynamics was typical to subtropical areas: maximum biomass during cold season from October to April and low biomass during summer months. The intensity of winter/spring bloom significantly varied during different years. The correlation was revealed between the summer/autumn air temperature contrast (expressed as the difference between the air temperatures in August and in November) and the maximum monthly averaged surface chlorophyll concentration during the subsequent winter/spring bloom. The features of seasonal dynamics of phytoplankton are regulated by the physical impacts influencing water stratification. The difference between two seasonal cycles (from September 1997 to October 1999) illustrates the response of phytoplankton growth to local meteorological conditions. In March–April 1999 the vernal bloom was much more pronounced; it resulted from deeper winter cooling and more intensive winter convection. Heating of surface water layer, wind mixing, and freshwater load with rains and river discharge either stimulate or depress the development of phytoplankton, depending on what limiting environmental factor (light or nutrient limitation) prevailed.
Energetic ion characteristics and neutral gas interactions in Jupiter's magnetosphere
Authors: Mauk B. H. , Mitchell D. G. , McEntire R. W. , Paranicas C. P. , Roelof E. C. , Williams D. J. , Krimigis S. M. , Lagg A.
Published: July 2004

Spectra, integral moments, and composition (H, He, O, S) of energetic ions (50 keV to 50 MeV) are presented for selected Jupiter magnetospheric positions near the equator between radial distances of ∼6 to ∼46 Jupiter radii (RJ), as revealed by analysis of the Galileo Energetic Particle Detector data. These characteristics are then used as the basis of interpreting and modeling reported signatures of energetic ion/neutral gas interactions within Jupiter's inner magnetosphere, particularly energetic neutral atom emissions measured during the Cassini spacecraft flyby of Jupiter. Key findings include the following: (1) sulfur ions significantly dominate the energetic (≥50 keV) ion density and pressure at all radial distances >7 RJ; (2) protons dominate integral number and energy intensity planetward of 20–25 RJ; (3) a distinct signature of local, equatorial acceleration of energetic protons is revealed between Io (5.9 RJ) and Europa (9.4 RJ); (4) significant spectral and compositional signatures of neutral gas interactions are also revealed between the orbits of Io and Europa; (5) a previously reported significant depletion of ring current ion populations between Io and Europa during the early‐phase operation of Galileo (∼1995), as compared with observations obtained during the Voyager epoch (1979), has persisted and probably deepened during later Galileo phases (1999); and (6) detailed energetic neutral atom emission modeling, based on the in situ results reported here, further constrains recent estimates of the contents of the neutral gas torus of Europa.
Asperity map along the subduction zone in northeastern Japan inferred from regional seismic data
Authors: Yamanaka Yoshiko , Kikuchi Masayuki
Published: July 2004

In an attempt to examine the characteristic behavior of asperities, we studied the source processes of large interplate earthquakes offshore of the Tohoku district, northeastern Japan, over the past 70 years. In this area, earthquakes of M7 class have a recurrence interval of about 30 years. Seismic observation using a strong‐motion seismometer has been carried out by the Japan Meteorological Agency since the beginning of the 1900s. We collected these seismograms in order to make a waveform inversion. On the basis of the derived heterogeneous fault slip, we identified large slip areas (asperities) for eight earthquakes which occurred after 1930, and we constructed an asperity map. The typical size of individual asperities in northeastern Japan is M7 class, and an M8 class earthquake can be caused when several asperities are synchronized. We propose that the patterns of asperity distribution beneath offshore Tohoku fall into three different categories. In the northern part (40°–41.3°N) the seismic coupling in the asperity is almost 100%, and the size is large. In the central part (39°–40°N), little seismic moment has been released by large earthquakes, and the asperity size is small. In the southern part (37.8°–39°N) the seismic coupling is medium. The weak seismic coupling may be related to submarine topographical features and to the sediment and water along the subducting plate. Our results also suggest a general tendency for the asperities to be located away from the hypocenters (initial break), with aftershocks occurring in the area surrounding the asperity.
Influence of mixing on CFC uptake and CFC ages in the North Pacific thermocline
Authors: Mecking Sabine , Warner Mark J. , Greene Catherine E. , Hautala Susan L. , Sonnerup Rolf E.
Published: July 2004

A diagnostic, isopycnal advection‐diffusion model based on a climatological, geostrophic flow field is used to study the uptake of chlorofluorocarbons (CFCs) into the portion of the thermocline that outcrops in the open North Pacific (σθ ≤ 26.6 kg m−3). In addition to advection, isopycnal diffusion is required to match the CFC data collected during the World Ocean Circulation Experiment (WOCE) in the early 1990s. Using reduced outcrop saturations of 80–95% for isopycnals outcropping in the northwestern North Pacific (σθ ≥ 25.4 kg m−3), together with an isopcynal interior diffusivity of 2000 m2 s−1 and enhanced diffusion (5000 m2 s−1) in the Kuroshio Extension region, further improves the model‐data agreement. Along‐isopycnal diffusion is particularly important for isopycnals with shadow zones/pool regions in the western subtropical North Pacific that are isolated from direct advective ventilation. The isopycnal mixing causes an estimated increase in CFC‐12 inventories on these isopycnals, compared to advection only, ranging from 10–20% (σθ = 25.6 kg m−3) to 50–130% (σθ = 26.6 kg m−3) over the subtropics in 1993. This contribution has important consequences for subduction rate estimates derived from CFC inventories and for the location of the subsurface CFC maxima. When tracer ages are derived from the modeled CFC distributions, time‐evolving mixing biases become apparent that reflect the nonlinearities in the atmospheric CFC time histories. Comparison with model‐calculated ideal ages suggests that during the time of WOCE (∼1993), ventilation ages based on CFC‐12 were biased young by as much as 16–24 years for pCFC‐12 ages of 25 years, underestimating ideal ages by as much as 40–50%.
Light scattering by fine particles during the Pittsburgh Air Quality Study: Measurements and modeling
Authors: Cabada Juan C. , Khlystov Andrey , Wittig Ann E. , Pilinis Christodoulos , Pandis Spyros N.
Published: July 2004

Light scattering by fine particulate matter was measured during the Pittsburgh Air Quality Study (PAQS) as close to ambient conditions as possible. Several approaches are used for the theoretical calculation of the scattering coefficient and the results are compared to the direct measurements. The first approach uses ambient high time and daily resolved PM2.5 composition concentrations to estimate the scattering coefficient assuming that the aerosol is an external mixture. The second approach uses a thermodynamic model and Mie theory to predict the scattering coefficient of aerosols from daily size composition distributions. The third approach introduces high time and daily resolved ambient aerosol water concentrations and concentrations of sulfate, nitrate, organic material, and soil with fixed scattering efficiencies. During the summer the first two approaches underestimate the measured scattering coefficient by around 20%. Agreement within experimental error is obtained between the measured scattering coefficient and the model, incorporating measured water aerosol concentrations. During the winter the first two approaches tend to overpredict the measured scattering by around 15%. This overprediction is weakly correlated to the organic mass. The modeling approaches suggest that sulfate and the associated water contribute 65–73% to the scattering coefficient during the summer, with organic material contributing 25–30%. During the winter, sulfate accounts for 35–43%, nitrate accounts for 24–32%, and organic material accounts for 30–40% of the scattering coefficient.
Chemical composition of air masses transported from Asia to the U.S. West Coast during ITCT 2K2: Fossil fuel combustion versus biomass‐burning signatures
Authors: de Gouw J. A. , Cooper O. R. , Warneke C. , Hudson P. K. , Fehsenfeld F. C. , Holloway J. S. , Hübler G. , Nicks Jr. D. K. , Nowak J. B. , Parrish D. D. , Ryerson T. B. , Atlas E. L. , Donnelly S. G. , Schauffler S. M. , Stroud V. , Johnson K. , Carmichael G. R. , Streets D. G.
Published: July 2004

As part of the Intercontinental Transport and Chemical Transformation experiment in 2002 (ITCT 2K2), a National Oceanic and Atmospheric Administration (NOAA) WP‐3D research aircraft was used to study the long‐range transport of Asian air masses toward the west coast of North America. During research flights on 5 and 17 May, strong enhancements of carbon monoxide (CO) and other species were observed in air masses that had been transported from Asia. The hydrocarbon composition of the air masses indicated that the highest CO levels were related to fossil fuel use. During the flights on 5 and 17 May and other days, the levels of several biomass‐burning indicators increased with altitude. This was true for acetonitrile (CH3CN), methyl chloride (CH3Cl), the ratio of acetylene (C2H2) to propane (C3H8), and, on May 5, the percentage of particles measured by the particle analysis by laser mass spectrometry (PALMS) instrument that were attributed to biomass burning based on their carbon and potassium content. An ensemble of back‐trajectories, calculated from the U.S. west coast over a range of latitudes and altitudes for the entire ITCT 2K2 period, showed that air masses from Southeast Asia and China were generally observed at higher altitudes than air from Japan and Korea. Emission inventories estimate the contribution of biomass burning to the total emissions to be low for Japan and Korea, higher for China, and the highest for Southeast Asia. Combined with the origin of the air masses versus altitude, this qualitatively explains the increase with altitude, averaged over the whole ITCT 2K2 period, of the different biomass‐burning indicators.
Elasticity of post‐perovskite MgSiO3
Authors: Tsuchiya Taku , Tsuchiya Jun , Umemoto Koichiro , Wentzcovitch Renata M.
Published: July 2004

We have determined by first principles the athermal elastic constant tensor, single crystal and aggregated acoustic velocities, and anisotropy of the recently discovered post‐perovskite MgSiO3 polymorph. This phase may be the most abundant mineral in the D″ region. We find that the post‐perovskite phase has similar bulk modulus and larger shear modulus than perovskite at relevant pressures. This phase is remarkably anisotropic. Analyses of horizontal shear wave splittings in transversely isotropic aggregates indicate that diverse lattice preferred orientations could produce large variation in anisotropy consistent with seismic observations in D″.
Vertical‐axis rotations determined from paleomagnetism of Mesozoic and Cenozoic strata of the Bolivian Andes
Authors: Richards David R. , Butler Robert F. , Sempere Thierry
Published: July 2004

Thermal demagnetization and principal component analysis allowed determination of characteristic remanent magnetization (ChRM) directions from 256 sites at 22 localities in Mesozoic and Cenozoic sedimentary strata of the Bolivian Altiplano and Eastern Cordillera. An inclination‐only fold test of site‐mean ChRM directions from Cenozoic units (principally the Santa Lucía Formation) indicates optimum unfolding at 97.1% unfolding, consistent with a primary origin for the ChRM. For Mesozoic strata, optimum unfolding occurred at 89.2%, perhaps indicating secondary remagnetization at some locations. For Cenozoic units, comparison of locality‐mean directions with expected paleomagnetic directions indicates vertical‐axis rotations from 33° counterclockwise to 24° clockwise. Euler pole analysis of along‐strike variation in crustal shortening within the Subandean and Interandean zones indicates 18° clockwise rotation south of the axis of curvature of the Bolivian Andes and 6° counterclockwise rotation northwest of the axis during the past 10 m.y. Along‐strike variation of shortening within the Eastern Cordillera indicates 8° clockwise rotation south of the axis and 8° counterclockwise rotation northwest of the axis from 35 to 10 Ma. These vertical‐axis rotations produced by along‐strike variations in crustal shortening during development of the Bolivian fold‐thrust belt agree well with observed rotations determined from paleomagnetism of Cenozoic rocks in the Eastern Cordillera and in the Subandean and Interandean zones. However, local rotations are required to account for complex rotations in the Cochabamba Basin and within the Altiplano. The curvature of the Bolivian Andes has been progressively enhanced during Cenozoic fold‐thrust belt deformation.
Inverse modeling of aerosol dynamics: Condensational growth
Authors: Henze D. K. , Seinfeld J. H. , Liao W. , Sandu A. , Carmichael G. R.
Published: July 2004

The feasibility of inverse modeling a multicomponent, size‐resolved aerosol evolving by condensation/evaporation is investigated. The adjoint method is applied to the multicomponent aerosol dynamic equation in a box model (zero‐dimensional) framework. Both continuous and discrete formulations of the model (the forward equation) and the adjoint are considered. A test example is studied in which the initial aerosol size composition distribution and the pure component vapor concentrations (i.e., vapor pressures) are estimated on the basis of measurements of all species, or a subset of the species, and the entire size distribution, or a portion of the size distribution. It is found that the adjoint method can successfully retrieve the initial size distribution and the pure component vapor concentrations even when only a subset of the species or a portion of the size distribution is observed, although this success is shown to depend upon the form of the initial estimates, the nature of the observations, and the length of the assimilation period. The results presented here provide a basis for the inverse modeling of aerosols in three‐dimensional atmospheric chemical transport models.
Identification and pharmacological characterization of native, functional human urotensin‐II receptors in rhabdomyosarcoma cell lines
Authors: Douglas Stephen A , Naselsky Diane , Ao Zhaohui , Disa Jyoti , Herold Christopher L , Lynch Frank , Aiyar Nambi V
Published: July 2004

In an effort to identify endogenous, native mammalian urotensin‐II (U‐II) receptors (UT), a diverse range of human, primate and rodent cell lines (49 in total) were screened for the presence of detectable [125I]hU‐II binding sites.

UT mRNA (Northern blot, PCR) and protein (immunocytochemistry) were evident in human skeletal muscle tissue and cells.

[125I]hU‐II bound to a homogenous population of high‐affinity, saturable (Kd 67.0±11.8 pM, Bmax 9687±843 sites cell−1) receptors in the skeletal muscle (rhabdomyosarcoma) cell line SJRH30. Radiolabel was characteristically slow to dissociate (15% dissociation 90 min). A lower density of high‐affinity U‐II binding sites was also evident in the rhabdomyosarcoma cell line TE671 (1667±165 sites cell−1, Kd 74±8 pM).

Consistent with the profile recorded in human recombinant UT‐HEK293 cells, [125I]hU‐II binding to SJRH30 cells was selectively displaced by both mammalian and fish U‐II isopeptides (Kis 0.5±0.1–1.2±0.3 nM) and related analogues (hU‐II[4‐11]>[Cys5,10]Acm hU‐II; Kis 0.4±0.1 and 864±193 nM, respectively).

U‐II receptor activation was functionally coupled to phospholipase C‐mediated [Ca2+]i mobilization (EC50 6.9±2.2 nM) in SJRH30 cells.

The present study is the first to identify the presence of ‘endogenous’ U‐II receptors in SJRH30 and TE671 cells. SJRH30 cells, in particular, might prove to be of utility for (a) investigating the pharmacological properties of hU‐II and related small molecule antagonists at native human UT and (b) delineating the role of this neuropeptide in the (patho)physiological regulation of mammalian neuromuscular function.

British Journal of Pharmacology (2004) 142, 921–932. doi:10.1038/sj.bjp.0705743
Interactions between NMDA receptors and mGlu5 receptors expressed in HEK293 cells
Authors: Collett Valerie J , Collingridge Graham L
Published: July 2004

Ca2+ imaging was used to investigate interactions between responses induced by N‐methyl‐D‐aspartate (NMDA; 15 μM) and (RS)‐3,5‐dihydroxyphenyl‐glycine (DHPG; 30 μM) in human embryonic kidney (HEK) 293 cells, transiently transfected with rat recombinant NR1a, NR2A and mGlu5a cDNA.

Responses to NMDA were reversibly depressed by DHPG from 244±14 to 194±12% of baseline. Treatment with thapsigargin (1 μM, 10 min) prevented this effect.

After thapsigargin pretreatment, repeated applications of NMDA showed a gradual rundown in amplitude over a period of several hours, and were unaffected by DHPG.

Continuous perfusion with staurosporine (0.1 μM), after thapsigargin pretreatment, converted the run‐down to a small increase in NMDA responses to 123±6 % of baseline. DHPG induced a further and sustained potentiation of NMDA responses to 174±12% of the initial baseline.

The protein tyrosine kinase (PTK) inhibitors genistein (50 μM) and 3‐(4‐chlorophenyl)1‐(1,1‐dimethylethyl)‐1H‐pyrazolo[3,4‐d]pyrimidin‐4‐amine (PP2; 1 μM) inhibited the staurosporine‐ and DHPG‐induced potentiation of NMDA responses.

The protein phosphatase (PTP) inhibitors orthovanadate (100 μM) and phenyl arsine oxide (PAO, 1 μM) facilitated the staurosporine‐evoked potentiation of NMDA responses and occluded DHPG‐induced potentiation.

In conclusion, complex interactions can be demonstrated between mGlu5 and NMDA receptors expressed in HEK293 cells. There is a negative inhibitory influence of Ca2+ release and PKC activation. Inhibition of these processes reveals a tonic, mGlu5 receptor and PTK‐dependent potentiation of NMDA receptors that can be augmented by either stimulating mGlu5 receptors or by inhibiting PTPs.

British Journal of Pharmacology (2004) 142, 991–1001. doi:10.1038/sj.bjp.0705861
Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart
Authors: Wang Ningyuan , Minatoguchi Shinya , Chen Xuehai , Uno Yoshihiro , Arai Masazumi , Lu ChuanJiang , Takemura Genzou , Fujiwara Takako , Fujiwara Hisayoshi
Published: July 2004

We examined whether antidiabetic drug miglitol could reduce ischaemia/reperfusion‐induced myocardial apoptosis by attenuating production.

Japanese white rabbits were subjected to 30‐min coronary occlusion followed by 4‐h reperfusion with miglitol (10 mg kg−1, i.v., n=20) or saline (n=20). The infarct area was determined by myoglobin staining, and the infarct size (IS) was expressed as a percentage of the area at risk. DNA fragmentation was assessed by TUNEL method and DNA ladder formation. The expression of Bcl‐XL and Bax was detected by immunohistochemical analysis and Western blot analysis. Myocardial interstitial 2,5‐DHBA levels, an indicator of hydroxyl radicals, were measured during 30‐min ischaemia and 30‐min reperfusion in the absence (n=10) or presence of miglitol (10 mg kg−1, i.v., n=10) using a microdialysis technique.

The IS was significantly reduced in the miglitol group (22.4±3.4%, n=10) compared to the control group (52.8±3.5%, n=10). Miglitol significantly decreased the 2,5‐DHBA level during ischaemia and reperfusion and suppressed the incidence of TUNEL‐positive myocytes in the ischaemic region (from 10.7±3.4 to 4.1±3.0%) and the intensity of DNA ladder formation. Miglitol significantly decreased the incidence of Bax‐positive myocytes in the ischaemic region (7.4±1.7 vs 13.7±1.9% of the control) and significantly attenuated the upregulation of Bax protein in the ischaemic regions (from 179±17 to 90±12% of sham). There was no difference in the expression of Bcl‐XL between the two groups.

These data suggest that miglitol reduces myocardial apoptosis by attenuating production of hydroxyl radicals and suppressing the upregulation of the expression of Bax protein.

British Journal of Pharmacology (2004) 142, 983–990. doi:10.1038/sj.bjp.0705863
Regulation of metalloproteinases and NF‐κB activation in rabbit synovial fibroblasts via E prostaglandins and Erk: contrasting effects of nabumetone and 6MNA
Authors: Pillinger Michael H , Dinsell Victoria , Apsel Beth , Tolani Sonia N , Marjanovic Nada , Chan Edwin S L , Gomez Paul , Clancy Robert , Chang Lih‐Fan , Abramson Steven B
Published: July 2004

Nabumetone is a prodrug that is converted in vivo into 6‐methoxy‐2‐naphthylacetic acid (6MNA), a cyclooxygenase inhibitor with anti‐inflammatory properties. We tested the effects of nabumetone and 6MNA on the inflammatory responses of synovial fibroblasts (SFs).

Brief exposures to 6MNA (50–150 μM) had no effect on IL‐1β/TNF‐α (each 20 ng ml−1)‐stimulated Erk activation. Longer exposures depleted prostaglandin E1 (PGE1) as much as 70%, and stimulated Erk as much as 300%. Nabumetone (150 μM) inhibited Erk activation by 60–80%.

6MNA (50–150 μM) stimulated (∼200%) and nabumetone (150 μM) inhibited (∼50%) matrix metalloproteinase (MMP)‐1, but not MMP‐13 secretion from SFs. 6MNA stimulation of MMP‐1 secretion was inhibited ∼30% by PGE1 (1 μM) and ∼80% by the Erk pathway inhibitor UO126 (10 μM), confirming that PGE depletion and Erk activation mediate MMP‐1 secretion by 6MNA.

Consistent with its role as an Erk inhibitor, nabumetone (150 μM) abrogated 6MNA enhancement of MMP‐1 secretion.

UO126 (10 μM) and nabumetone (150 μM) inhibited (∼70 and 40%, respectively), but 6MNA (150 μM) enhanced (∼40%), NF‐κB activation.

Our data indicate that 6MNA shares with other COX inhibitors several proinflammatory effects on synovial fibroblasts. In contrast, nabumetone demonstrates anti‐inflammatory and potentially arthroprotective effects that have not been previously appreciated.

British Journal of Pharmacology (2004) 142, 973–982. doi:10.1038/sj.bjp.0705864
Possible mechanism of action of the histone deacetylase inhibitors for the induction of differentiation of HL‐60 clone 15 cells into eosinophils
Authors: Ishihara Kenji , Hong JangJa , Zee OkPyo , Ohuchi Kazuo
Published: July 2004

We have examined the effect of the histone deacetylase inhibitors apicidin, trichostatin A (TSA) and n‐butyrate on the histone acetylation and the differentiation of human eosinophilic leukemia HL‐60 clone 15 cells into eosinophils.

Viability of the cells incubated with apicidin (100 nM), TSA (30 nM) or n‐butyrate (500 μM) did not change significantly, but higher concentrations of apicidin (300 nM) or TSA (100 nM) decreased the viability when examined at day 1.

Apicidin (100 nM) as well as n‐butyrate (500 μM) induced continuous acetylations of histone H4 and lysine14 residue on histone H3, while TSA (30 nM) induced transient acetylations.

After 6 days incubation, eosinophilic cells stained by Luxol‐fast‐blue were generated by apicidin (100 nM) and n‐butyrate (500 μM) but not by TSA (30 nM). Other markers for differentiation into eosinophils such as changes in intracellular structure, and expressions of integrin β7 and major basic protein, and the inhibition of cell proliferation were also induced by apicidin and n‐butyrate but not by TSA.

Continuous acetylation of histone H4 achieved by repeated treatment with TSA (30 nM) at an interval of 12 h for more than three times induced such changes when examined on day 6. In addition, the induction was impaired by shortening the period of incubation with apicidin (100 nM) or n‐butyrate (500 μM).

CCAAT/enhancer binding protein was continuously activated by apicidin (100 nM) and n‐butyrate (500 μM), but was transiently activated by TSA (30 nM).

These findings suggest that the continuous acetylation of histones H3 and H4 is necessary for the differentiation of HL‐60 clone 15 cells into eosinophils.

British Journal of Pharmacology (2004) 142, 1020–1030. doi:10.1038/sj.bjp.0705869
Inhibition of c‐Jun N‐terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats
Authors: Ferrandi Chiara , Ballerio Rossana , Gaillard Pascale , Giachetti Claudio , Carboni Sonia , Vitte Pierre‐Alain , Gotteland Jean‐Pierre , Cirillo Rocco
Published: July 2004

Myocardial ischemia/reperfusion is associated with inflammation, apoptosis and necrosis. During this process, c‐jun N‐terminal kinase is activated in cardiac myocytes resulting in apoptosis.

This study investigates the effects of AS601245, a nonpeptide ATP competitive JNK inhibitor, on infarct size caused by myocardial ischemia/reperfusion in anaesthetized rats. The left descending coronary artery of anaesthetized rats was occluded for 30 min and then reperfused for 3 h. AS601245 was administered 5 min before the end of the ischemia period as an i.v. bolus (1.5, 4.5 or 15 mg kg−1 i.v.) followed by continuous i.v. infusion (18, 55 and 183 μg kg−1 min−1, respectively) during reperfusion. Controls received saline only. 3‐Aminobenzamide, a poly(ADP‐ribose) polymerase inhibitor, was used as reference compound at 10 mg kg−1 i.v. bolus plus 0.17 mg kg−1 min−1 continuous infusion.

AS601245 significantly reduced infarct size at 4.5 mg kg−1 (−44%; P<0.001) and 15 mg kg−1 i.v. (−40.3%; P<0.001) similarly to 3‐aminobenzamide (−44.2%; P<0.001). This protective effect was obtained without affecting hemodinamics or reducing ST‐segment displacement.

The beneficial effects on infarct size correlated well with the reduction of c‐jun phosphorylation (−85%; P<0.001 versus control) and of TUNEL‐positive cells (−82.1%; P<0.001) in post‐ischemic cardiomyocytes. No change in the phosphorylation state of p38 MAPK and ERK in post‐ischemic heart was observed in the presence of AS601245 in comparison to the vehicle‐treated group.

These results demonstrate that blocking the JNK pathway may represent a novel therapeutic approach for treating myocardial ischemia/reperfusion‐induced cardiomyocyte death.

British Journal of Pharmacology (2004) 142, 953–960. doi:10.1038/sj.bjp.0705873
Central effects of the cannabinoid receptor agonist WIN55212‐2 on respiratory and cardiovascular regulation in anaesthetised rats
Authors: Pfitzer Torsten , Niederhoffer Nathalie , Szabo Bela
Published: July 2004

The primary aim was to study the central respiratory effects of cannabinoids (CB). To this end, the cannabinoid receptor agonist WIN55212‐2 was injected into the cisterna magna of urethane‐anaesthetised rats and changes in respiratory parameters were observed. The secondary aim was to observe the centrally elicited cardiovascular actions of WIN55212‐2. Involvement of opioid mechanisms in the central effects of WIN55212‐2 was also studied.

Intracisternal (i.c.) application of WIN55212‐2 (1, 3, 10 and 30 μg kg−1) dose‐dependently decreased the respiratory rate and minute volume. Tidal volume was slightly increased, whereas peak inspiratory flow remained unchanged. In addition, WIN55212‐2 increased mean arterial pressure and the plasma noradrenaline concentration and decreased heart rate. I.c. injection of WIN55212‐3 (1, 3, 10 and 30 μg kg−1), an enantiomer of WIN55212‐2 lacking affinity for cannabinoid receptors, elicited no effects. All effects of WIN55212‐2 were prevented by the CB1 receptor antagonist SR141716 (2 mg kg−1 i.v.).

I.c. administration of the opioid receptor agonist DAMGO (0.1, 0.3, 1 and 3 μg kg−1) markedly lowered the respiratory rate, tidal volume, minute volume and peak inspiratory flow. These effects were attenuated by the opioid receptor antagonist naloxone (0.2 mg kg−1 i.v.). In contrast, naloxone did not affect the respiratory and cardiovascular effects of i.c. administered WIN55212‐2.

Our results show that activation of CB1 cannabinoid receptors in the brain stem depresses respiration and enhances sympathetic tone and cardiac vagal tone. Opioid mechanisms are not involved in these central cannabinoid effects.

British Journal of Pharmacology (2004) 142, 943–952. doi:10.1038/sj.bjp.0705874
Peripheral GABAB agonists stimulate gastric acid secretion in mice
Authors: Piqueras Laura , Martinez Vicente
Published: July 2004

We characterized the effects of intravenous GABA and preferential GABAA (muscimol), GABAB (R‐baclofen and SKF‐97541) and GABAC agonists (imidazole‐4‐acetic acid) on gastric acid secretion in urethane‐anesthetized mice implanted with a gastric cannula, and determined the role of vagal cholinergic mechanisms, and gastrin and somatostatin by using peptide immunoneutralization, the SSTR2 antgonist, PRL‐2903, and SSTR2 knockout mice.

The selective GABAB agonists R‐baclofen (0.1–3 mg kg−1, i.v.) and SKF‐97541 (0.01–0.3 mg kg−1, i.v.) induced a dose‐related stimulation of gastric acid secretion. SKF‐97541 was about 10 times more potent than R‐baclofen stimulating gastric acid secretion. Neither GABA (0.1–100 mg kg−1, i.v.) nor muscimol (0.1–3 mg kg−1) nor imidazole‐4‐acetic acid (0.1–10 mg kg−1) affected basal gastric acid secretion.

Stimulatory effects of SKF‐97541 (0.1 mg kg−1, i.v.) were blocked by the selective GABAB antagonist, 2‐hydroxysaclofen, cholinergic blockade with atropine, subdiaphragmatic vagotomy or gastrin immunoneutralization.

Somatostatin immunoneutralization or SSTR2 blockade with PRL‐2903 enhanced the secretory response to SKF‐97541 (0.1 mg kg−1, i.v.) by 78 and 105%, respectively.

In SSTR2 knockout mice, SKF‐97541 (0.1 mg kg−1, i.v.) increased basal gastric acid secretion by 48%. Neither GABA nor muscimol nor imidazole‐4‐acetic acid modified basal gastric acid secretion in SSTR2 knockout mice.

These results indicate that, in mice, stimulation of GABAB receptors increases gastric acid secretion through vagal‐ and gastrin‐dependent mechanisms. Somatostatin implication might be secondary to the release of gastrin and the increase in gastric luminal acidity.

British Journal of Pharmacology (2004) 142, 1038–1048. doi:10.1038/sj.bjp.0705876
Ligands of the peroxisome proliferator‐activated receptor‐γ and heart failure
Authors: Thiemermann Christoph
Published: July 2004

This Commentary originally appeared in the British Journal of Pharmacology in January 2004 (Br J Pharmacol 141 (1), 1–3). That version, regrettably, contained a number of errors and the corrected version is printed here, as an Erratum.

Peroxisome proliferator‐activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand‐activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR‐α, PPAR‐β and PPAR‐γ. There is good evidence that ligands of PPAR‐γ, including certain thiazolinediones, reduce myocardial tissue injury and infarct size. The use of PPAR‐γ agonists in the treatment of heart failure is, however, controversial.

British Journal of Pharmacology (2004) 142, 1049–1051. doi:10.1038/sj.bjp.0705898
Crystal structure of human otubain 2
Authors: Nanao Max H , Tcherniuk Sergey O , Chroboczek Jadwiga , Dideberg Otto , Dessen Andréa , Balakirev Maxim Y
Published: July 2004

Ubiquitylation, the modification of cellular proteins by the covalent attachment of ubiquitin, is critical for diverse biological processes including cell cycle progression, signal transduction and stress response. This process can be reversed and regulated by a group of proteases called deubiquitylating enzymes (DUBs). Otubains are a recently identified family of DUBs that belong to the ovarian tumour (OTU) superfamily of proteins. Here, we report the first crystal structure of an OTU superfamily protein, otubain 2, at 2.1 Å resolution and propose a model for otubain–ubiquitin binding on the basis of other DUB structures. Although otubain 2 is a member of the cysteine protease superfamily of folds, its crystal structure shows a novel fold for DUBs. Moreover, the active‐site cleft is sterically occluded by a novel loop conformation resulting in an oxyanion hole, which consists uniquely of backbone amides, rather than the composite backbone/side‐chain substructures seen in other DUBs and cysteine proteases. Furthermore, the residues that orient and stabilize the active‐site histidine of otubain 2 are different from other cysteine proteases. This reorganization of the active‐site topology provides a possible explanation for the low turnover and substrate specificity of the otubains.
Analysis of developing maize plastids reveals two mRNA stability classes correlating with RNA polymerase type
Authors: Cahoon A Bruce , Harris Faith M , Stern David B
Published: July 2004

The plastid genome is transcribed by two distinct RNA polymerases, the PEP encoded by the plastid genome and the NEP encoded in the nucleus. Initial models of plastid transcription held that the NEP is responsible for the transcription of housekeeping genes needed early in development, and that the PEP transcribes genes required for photosynthesis. Recently, this model was challenged by the discovery that all plastid genes are transcribed by NEP in PEP‐deficient tobacco plastids, suggesting that mRNA turnover may have a strong role in previously observed transcription patterns. In this study, we provide evidence that the NEP enzyme level decreases as plastids mature. In contrast, production of mRNAs by NEP increases as plastids mature, yet their accumulations remain constant. These results suggest that as plastids mature NEP may become more active, and that mRNA turnover varies between transcripts synthesized by NEP and PEP.
Cyclooxygenasen in der Haut
Authors: Müller‐Decker Karin
Published: July 2004

Cyclooxygenasen (COX)‐1 und COX‐2 sind die Schrittmacherenzyme in der Prostaglandinbiosynthese und repräsentieren die molekularen Targets für nicht‐steroidale Entzündungshemmer. In gesunden Geweben von Erwachsenen wird in der Regel COX‐1, nicht jedoch COX‐2 exprimiert. Nach Schnittverletzung der Haut oder Auslösung einer akuten irritativen Kontaktdermatitis wird COX‐2 transient in der Epidermis gebildet. Insbesondere die Entwicklung von UV‐induziertem Erythem und Ödem aber auch von Hauttumoren werden maßgeblich durch die Aktivität von COX‐2 beeinflußt. Plattenepithelkarzinome und aktinische Keratosen der Haut gelten als ein prominentes Beispiel von epithelialen Tumoren, für die eine permanente Überexpression der COX‐2 im Tumorparenchym, im entzündlichen Tumorinfiltrat und in Tumorgefäßen ein hervorstechendes Merkmal ist. Mehrstufenkarzinogeneseversuchen in der Maushaut und Experimenten mit transgenen Mäusen zufolge besteht ein kausaler Zusammenhang zwischen aberranter COX‐2‐Expression und Aktivität im Epithel und der Tumorpromotion und ‐progression. Die transgene Überexpression der COX‐2 verursacht nämlich einen autopromovierten Hautphänotyp, d. h. das Enzym sensibilisiert das Gewebe drastisch für die Entwicklung von Plattenepithelkarzinomen. Umgekehrt führt die genetische Ausschaltung der COX‐2, aber auch der COX‐1, in der Maushaut zu einer reduzierten Tumorlast. Die Störung der terminalen Differenzierung der Epidermis scheint ein Hauptmechanismus zu sein, wie COX‐2 zur epidermalen Tumorbildung beiträgt. Aufgrund dieser Erkenntnisse werden COX‐2‐selektive Inhibitoren als vielversprechende Substanzen zur Prävention und Therapie von Hautkrebs eingestuft.
The evolution of reproductive restraint through social communication
Authors: Werfel Justin , Bar-Yam Yaneer
Published: July 2004

The evolution of altruistic behavior through group selection is generally viewed as possible in theory but unlikely in reality, because individual selection favoring selfish strategies should act more rapidly than group selection favoring cooperation. Here we demonstrate the evolution of altruism, in the form of conditional reproductive restraint based on an explicitly social mechanism, modulated by intrapopulation communication comprising signal and evolved response, in a spatially distributed predatory/parasitic/pathogenic model system. The predatory species consistently comes to exploit a signal implying overcrowding, individuals constraining their reproduction in response, with a corresponding increase in equilibrium reproduction rate in the absence of signal. This signaled restraint arises in a robust way for a range of model spatial systems; it outcompetes non-signal-based restraint and is not vulnerable to subversion by noncooperating variants. In these systems, communication is used to evaluate population density and regulate reproduction accordingly, consistent with central ideas of Wynne-Edwards [Wynne-Edwards, V. C. (1962)Animal Dispersion in Relation to Social Behavior(Hafner, New York)], whose claims about the evolutionary importance of group selection helped ignite decades of controversy. This quantitative simulation model shows how the key evolutionary transition from solitary living to sociality can occur. The process described here of cooperation evolving through communication may also help to explain other major evolutionary transitions such as intercellular communication leading to multicellular organisms.
Modeling a synthetic multicellular clock: Repressilators coupled by quorum sensing
Authors: Garcia-Ojalvo Jordi , Elowitz Michael B. , Strogatz Steven H.
Published: July 2004

Diverse biochemical rhythms are generated by thousands of cellular oscillators that somehow manage to operate synchronously. In fields ranging from circadian biology to endocrinology, it remains an exciting challenge to understand how collective rhythms emerge in multicellular structures. Using mathematical and computational modeling, we study the effect of coupling through intercell signaling in a population of
Escherichia coli
cells expressing a synthetic biological clock. Our results predict that a diverse and noisy community of such genetic oscillators interacting through a quorum-sensing mechanism should self-synchronize in a robust way, leading to a substantially improved global rhythmicity in the system. As such, the particular system of coupled genetic oscillators considered here might be a good candidate to provide the first quantitative example of a synchronization transition in a population of biological oscillators.
Expanded dynamic range of fluorescent indicators for Ca
2+
by circularly permuted yellow fluorescent proteins
Authors: Nagai Takeharu , Yamada Shuichi , Tominaga Takashi , Ichikawa Michinori , Miyawaki Atsushi
Published: July 2004

Fluorescence resonance energy transfer (FRET) technology has been used to develop genetically encoded fluorescent indicators for various cellular functions. Although most indicators have cyan- and yellow-emitting fluorescent proteins (CFP and YFP) as FRET donor and acceptor, their poor dynamic range often prevents detection of subtle but significant signals. Here, we optimized the relative orientation of the two chromophores in the Ca
2+
indicator, yellow cameleon (YC), by fusing YFP at different angles. We generated circularly permuted YFPs (cpYFPs) that showed efficient maturation and acid stability. One of the cpYFPs incorporated in YC absorbs a great amount of excited energy from CFP in its Ca
2+
-saturated form, thereby increasing the Ca
2+
-dependent change in the ratio of YFP/CFP by nearly 600%. Both in cultured cells and in the nervous system of transgenic mice, the new YC enables visualization of subcellular Ca
2+
dynamics with better spatial and temporal resolution than before. Our study provides an important guide for the development and improvement of indicators using GFP-based FRET.
Functional disassociation of the central and peripheral fatty acid amide signaling systems
Authors: Cravatt Benjamin F. , Saghatelian Alan , Hawkins Edward G. , Clement Angela B. , Bracey Michael H. , Lichtman Aron H.
Published: July 2004

Fatty acid amides (FAAs) constitute a large class of endogenous signaling lipids that modulate several physiological processes, including pain, feeding, blood pressure, sleep, and inflammation. Although FAAs have been proposed to evoke their behavioral effects through both central and peripheral mechanisms, these distinct signaling pathways have remained experimentally challenging to separate. Here, we report a transgenic mouse model in which the central and peripheral FAA systems have been functionally uncoupled. Mice were generated that express the principle FAA-degrading enzyme FAA hydrolase (FAAH) specifically in the nervous system (FAAH-NS mice) by crossing FAAH
-/-
mice with transgenic mice that express FAAH under the neural specific enolase promoter. FAAH-NS mice were found to possess wild-type levels of FAAs in the brain and spinal cord, but significantly elevated concentrations of these lipid transmitters in peripheral tissues. This anatomically restricted biochemical phenotype correlated with a reversion of the reduced pain sensitivity of FAAH
-/-
mice, consistent with the FAA anandamide producing this effect by acting on cannabinoid receptors in the nervous system. Interestingly, however, FAAH-NS mice still exhibited an antiinflammatory phenotype similar in magnitude to FAAH
-/-
mice, indicating that this activity, which was not blocked by cannabinoid receptor antagonists, was mediated by peripherally elevated FAAs. These data suggest that the central and peripheral FAA signaling systems regulate discrete behavioral processes and may be targeted for distinct therapeutic gain.
Direct measurement of proton release by cytochrome
c
oxidase in solution during the F→O transition
Authors: Zaslavsky Dmitry , Sadoski Robert C. , Rajagukguk Sany , Geren Lois , Millett Francis , Durham Bill , Gennis Robert B.
Published: July 2004

The mechanism by which electron transfer is coupled to proton pumping in cytochrome
c
oxidase is a major unsolved problem in molecular bioenergetics. In this work it is shown that, at least under some conditions, proton release from the enzyme occurs before proton uptake upon electron transfer to the heme/Cu active site of the enzyme. This sequence is similar to that of proton release and uptake observed for the light-activated proton pump bacteriorhodopsin. In the case of cytochrome
c
oxidase, this observation means that both the ejected proton and the proton required for the chemistry at the enzyme active site must come from an internal proton pool.
Abnormal sperm in mice with targeted deletion of the
act
(activator of cAMP-responsive element modulator in testis) gene
Authors: Kotaja Noora , De Cesare Dario , Macho Betina , Monaco Lucia , Brancorsini Stefano , Goossens Ellen , Tournaye Herman , Gansmuller Anne , Sassone-Corsi Paolo
Published: July 2004

ACT [activator of cAMP-responsive element modulator (CREM) in testis] is a LIM-only protein that interacts with transcription factor CREM in postmeiotic male germ cells and enhances CREM-dependent transcription. CREM regulates many crucial genes required for spermatid maturation, and targeted mutation of the
Crem
gene in the mouse germ-line blocks spermatogenesis. Here we report the phenotype of mice in which targeted disruption of the
act
gene was obtained by homologous recombination. Whereas the seminiferous tubules of the
act
–/–
mice contain all of the developmental stages of germ cells and the mice are fertile, the amount of mature sperm in the epididymis is drastically reduced. The residual sperm display severe abnormalities, including fully folded tails and aberrant head shapes. These results indicate that numerous postmeiotic genes under CREM control require the coactivator function of ACT. Thus, the fine-tuning of sperm development is achieved by the coordinated action of two transcriptional regulators.