bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Redox Factor 1 Decreases NF-κB Activity and Increases Susceptibility of Endothelial Cells to Apoptosis
Authors: Guan Zhanjun , Basi David , Li Qinglu , Mariash Ami , Xia Yi-Feng , Geng Jian-Guo , Kao Esther , Hall Jennifer L.
Published: November 2004

Objective—

The aim of this project was to test the hypothesis that redox factor 1 (Ref-1) was a critical upstream determinant of NF-κB–dependent survival signaling pathways in the vessel wall.

Methods and Results—

Aortas from hemizygous transgenic mice harboring a single allele of Ref-1 exhibited a significant loss in NF-κB DNA binding activity. The NF-κB–dependent survival gene A20 was significantly downregulated in aortas of hemizygous Ref-1 mice, whereas IAP-2 was unchanged. Overexpression of A20 rescued cells from tumor necrosis factor (TNF)-induced apoptosis, suggesting that the loss of A20 in Ref-1 hemizygotes may be a rate-determining step in endothelial cell fate. Deletion of the previously defined redox-sensitive or the AP endonuclease domains of Ref-1 significantly decreased NF-κB transcriptional activation and endothelial cell survival. Furthermore, TNF-induced apoptosis was significantly potentiated in endothelial cells after delivery of Morpholino antisense oligodeoxynucleotides targeted to Ref-1. Loss of the redox-sensitive domain blocked the ability of Ref-1 to reduce p50; however, loss of the endonuclease domain did not effect p50 reduction, suggesting alternative mechanisms of action of Ref-1 on NF-κB activity.

Conclusions—

These findings establish a role for Ref-1 as an upstream determinant of NF-κB and A20-dependent signaling and endothelial survival in the vessel wall.
Oxidative Stress and Vascular Disease
Authors: Madamanchi Nageswara R. , Vendrov Aleksandr , Runge Marschall S.
Published: November 2004

Growing evidence indicates that chronic and acute overproduction of reactive oxygen species (ROS) under pathophysiologic conditions is integral in the development of cardiovascular diseases (CVD). These ROS can be released from nicotinamide adenine dinucleotide (phosphate) oxidase, xanthine oxidase, lipoxygenase, mitochondria, or the uncoupling of nitric oxide synthase in vascular cells. ROS mediate various signaling pathways that underlie vascular inflammation in atherogenesis: from the initiation of fatty streak development through lesion progress to ultimate plaque rupture. Various animal models of oxidative stress support the notion that ROS have a causal role in atherosclerosis and other cardiovascular diseases. Human investigations also support the oxidative stress hypothesis of atherosclerosis. Oxidative stress is the unifying mechanism for many CVD risk factors, which additionally supports its central role in CVD. Despite the demonstrated role of antioxidants in cellular and animal studies, the ineffectiveness of antioxidants in reducing cardiovascular death and morbidity in clinical trials has led many investigators to question the importance of oxidative stress in human atherosclerosis. Others have argued that the prime factor for the mixed outcomes from using antioxidants to prevent CVD may be the lack of specific and sensitive biomarkers by which to assess the oxidative stress phenotypes underlying CVD. A better understanding of the complexity of cellular redox reactions, development of a new class of antioxidants targeted to specific subcellular locales, and the phenotype-genotype linkage analysis for oxidative stress will likely be avenues for future research in this area as we move toward the broader use of pharmacological and regenerative therapies in the treatment and prevention of CVD.
Transforming Growth Factor β Receptor Endoglin Is Expressed in Cardiac Fibroblasts and Modulates Profibrogenic Actions of Angiotensin II
Authors: Chen Kui , Mehta Jawahar L. , Li Dayuan , Joseph Lija , Joseph Jacob
Published: November 2004

Angiotensin II (Ang II) is a powerful mediator of adverse cardiac remodeling and fibrosis. However, the mechanisms of Ang II–induced myocardial fibrosis remain to be clarified. We postulated that Ang II alters transforming growth factor β (TGF-β) receptor expression, specifically that of endoglin, and thereby modulates cardiac fibroblast (CF) collagen metabolism. Experiments were conducted using CF from adult Sprague Dawley rats to determine the expression of TGF-β
1
receptors including endoglin, and the role of Ang II type 1 (AT
1
) and type 2 (AT
2
) receptors, and MAPK p42/44 in this process. The functional role of endoglin in modulating Ang II effects on matrix metalloproteinase-1 (MMP-1) and type I collagen expression was also analyzed. Endoglin gene and protein expression were consistently identified in quiescent CFs. Ang II increased the expression of endoglin mRNA and protein in a concentration and time-dependent manner, with no effect on TGF-β receptors I and II expression. This effect was AT
1
receptor mediated, because AT
1
receptor antagonists valsartan, candesartan, and losartan inhibited Ang II–induced endoglin expression, whereas the AT
2
receptor antagonist PD123319 had no effect. MAPKp42/44 inhibition attenuated Ang II–induced endoglin expression. Ang II–induced decrease in MMP-1 protein expression and increase in type I collagen protein expression were both blocked by a specific endoglin antibody. Hence, our results indicate that endoglin is upregulated in CFs by Ang II via the AT
1
receptor and modulates profibrotic effects of Ang II. These findings provide novel insights into Ang II–induced cardiac remodeling.
Molecular Imaging of Atherosclerotic Plaques Using a Human Antibody Against the Extra-Domain B of Fibronectin
Authors: Matter Christian M. , Schuler Pia K. , Alessi Patrizia , Meier Patricia , Ricci Romeo , Zhang Dongming , Halin Cornelia , Castellani Patrizia , Zardi Luciano , Hofer Christoph K. , Montani Matteo , Neri Dario , Lüscher Thomas F.
Published: November 2004

Current imaging modalities of human atherosclerosis, such as angiography, ultrasound, and computed tomography, visualize plaque morphology. However, methods that provide insight into plaque biology using molecular tools are still insufficient. The extra-domain B (ED-B) is inserted into the fibronectin molecule by alternative splicing during angiogenesis and tissue remodeling but is virtually undetectable in normal adult tissues. Angiogenesis and tissue repair are also hallmarks of advanced plaques. For imaging atherosclerotic plaques, the human antibody L19 (specific against ED-B) and a negative control antibody were labeled with radioiodine or infrared fluorophores and injected intravenously into atherosclerotic apolipoprotein E–null (
ApoE
−/−
) or normal wild-type mice. Aortas isolated 4 hours, 24 hours, and 3 days after injection exhibited a selective and stable uptake of L19 when using radiographic or fluorescent imaging. L19 binding was confined to the plaques as assessed by fat staining. Comparisons between fat staining and autoradiographies 24 hours after
125
I-labeled L19 revealed a significant correlation (
r
=0.89;
P
<0.0001). Minimal antibody uptake was observed in normal vessels from wild-type mice receiving the L19 antibody and in atherosclerotic vessels from
ApoE
−/−
mice receiving the negative control antibody. Immunohistochemical studies revealed increased expression of ED-B not only in murine but also in human plaques, in which it was found predominantly around vasa vasorum and plaque matrix. In summary, we demonstrate selective targeting of atheromas in mice using the human antibody to the ED-B domain of fibronectin. Thus, our findings may set the stage for antibody-based molecular imaging of atherosclerotic plaques in the intact organism.
Peptidyl-Glycine α-Amidating Monooxygenase Targeting and Shaping of Atrial Secretory Vesicles
Authors: Labrador Vénus , Brun Cécile , König Stéphane , Roatti Angela , Baertschi Alex J.
Published: November 2004

ANP (atrial natriuretic peptide) is widely recognized as an important vasorelaxant, diuretic, and cardioprotective hormone. Little is known, however, about how ANP-secretory vesicles form within the atrial myocytes. Secretory vesicles were visualized by fluorescence microscope imaging in live rat atrial myocytes expressing proANP–enhanced green fluorescent protein (EGFP), or N-terminal–mutated fusion proteins thought to suppress the calcium-dependent aggregation of proANP. Results showed the following: (1) aggregates of proANP and coexpressed proANP-EGFP recruited peptidylglycine α-amidating monooxygenase (PAM)-1, an abundant atrial integral vesicle membrane protein; (2) coexpressed N-terminal–mutated (Glu23,24→Gln23,24) and N-terminal–deleted proANP-EGFP inhibited recruitment of PAM-1 by up to 60%; (3) 4-phenyl-3-butenoic acid (PBA) (10 μmol/L), a pharmacological inhibitor of the lumenal peptidylglycine α-hydroxylating monooxygenase domain of PAM proteins, inhibited recruitment of endogenous PAM-1 and of coexpressed pro-EGFP–PAM-1; (4) PBA had no effect on exocytosis of the potassium inward rectifier KIR2.1; (5) PBA induced a deformation of the secretory vesicles but did not inhibit docking. These findings suggest that recruitment of PAM-1 to secretory vesicles depends on intact N-terminal proANP and on the lumenal domain of PAM-1. Conversely, PAM-1 participates in shaping the proANP-secretory vesicles. The full text of this article is available online at http://circres.ahajournals.org.
A Simplified Diagnostic Model of Orographic Rainfall for Enhancing Satellite-Based Rainfall Estimates in Data-Poor Regions
Authors: Funk Chris , Michaelsen Joel
Published: November 2004

An extension of Sinclair's diagnostic model of orographic precipitation (“VDEL”) is developed for use in data-poor regions to enhance rainfall estimates. This extension (VDELB) combines a 2D linearized internal gravity wave calculation with the dot product of the terrain gradient and surface wind to approximate terrain-induced vertical velocity profiles. Slope, wind speed, and stability determine the velocity profile, with either sinusoidal or vertically decaying (evanescent) solutions possible. These velocity profiles replace the parameterized functions in the original VDEL, creating VDELB, a diagnostic accounting for buoyancy effects. A further extension (VDELB*) uses an on/off constraint derived from reanalysis precipitation fields. A validation study over 365 days in the Pacific Northwest suggests that VDELB* can best capture seasonal and geographic variations. A new statistical data-fusion technique is presented and is used to combine VDELB*, reanalysis, and satellite rainfall estimates in southern Africa. The technique, matched filter regression (MFR), sets the variance of the predictors equal to their squared correlation with observed gauge data and predicts rainfall based on the first principal component of the combined data. In the test presented here, mean absolute errors from the MFR technique were 35% lower than the satellite estimates alone. VDELB assumes a linear solution to the wave equations and a Boussinesq atmosphere, and it may give unrealistic responses under extreme conditions. Nonetheless, the results presented here suggest that diagnostic models, driven by reanalysis data, can be used to improve satellite rainfall estimates in data-sparse regions.
Nocturnal Low-Level Jet in a Mountain Basin Complex. Part I: Evolution and Effects on Local Flows
Authors: Banta Robert M. , Darby Lisa S. , Fast Jerome D. , Pinto James O. , Whiteman C. David , Shaw William J. , Orr Brad W.
Published: November 2004

A Doppler lidar deployed to the center of the Great Salt Lake (GSL) basin during the Vertical Transport and Mixing (VTMX) field campaign in October 2000 found a diurnal cycle of the along-basin winds with northerly up-basin flow during the day and a southerly down-basin low-level jet at night. The emphasis of VTMX was on stable atmospheric processes in the cold-air pool that formed in the basin at night. During the night the jet was fully formed as it entered the GSL basin from the south. Thus, it was a feature of the complex string of basins draining toward the Great Salt Lake, which included at least the Utah Lake basin to the south. The timing of the evening reversal to down-basin flow was sensitive to the larger-scale north–south pressure gradient imposed on the basin complex. On nights when the pressure gradient was not too strong, local drainage flow (slope flows and canyon outflow) was well developed along the Wasatch Range to the east and coexisted with the basin jet. The coexistence of these two types of flow generated localized regions of convergence and divergence, in which regions of vertical motion and transport were focused. Mesoscale numerical simulations captured these features and indicated that updrafts on the order of 5 cm s−1 could persist in these localized convergence zones, contributing to vertical displacement of air masses within the basin cold pool.
A Momentum Exchange Model for the Surface Layer over Bare-Soil and Canopy-Covered Surfaces
Authors: Takahashi Atsuhiro , Hiyama Tetsuya
Published: November 2004

A multilayered turbulent transport model for the surface layer based on collisions between atmospheric layers is developed. The model can represent the average and perturbed components of turbulence relatively well, for both bare-soil and canopy-covered surfaces. The number of collisions increases linearly with height for a bare-soil surface, and decreases as the leaf-area density increases within the canopy layer. The intermittent nature of turbulent motion is reproduced in the model, even though the model is one-dimensional. The number of collisions increasing with height may cause the intermittent nature of the turbulence and may also relate to the gust motions for canopy flow; such gusts transfer large momentum downward intermittently and cause a secondary maximum in wind velocity in the lower layer within the canopy. In other words, the model can include the large-eddy effect by considering the different number of collisions among layers. Turbulence data measured with an ultrasonic anemometer at 10 Hz in the field were used as model input; plausible results were obtained. The model can represent the overall characteristics of turbulence in the surface layer.
The Effect of Model Resolution in Predicting Meteorological Parameters Used in Fire Danger Rating
Authors: Hoadley Jeanne L. , Westrick Ken , Ferguson Sue A. , Goodrick Scott L. , Bradshaw Larry , Werth Paul
Published: November 2004

Previous studies of model performance at varying resolutions have focused on winter storms or isolated convective events. Little attention has been given to the static high pressure situations that may lead to severe wildfire outbreaks. This study focuses on such an event so as to evaluate the value of increased model resolution for prediction of fire danger. The results are intended to lay the groundwork for using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) as input to the National Fire Danger Rating System to provide gridded predictions of fire danger indices. Predicted weather parameters were derived from MM5 and evaluated at three different resolutions (36, 12, and 4 km). Model output was compared with observations during the 2000 fire season in western Montana and northern Idaho to help to determine the model's skill in predicting fire danger. For application in fire danger rating, little significant improvement was found in skill with increased model resolution using standard forecast verification techniques. Diurnal bias of modeled temperature and relative humidity resulted in errors larger than the differences between resolutions. Significant timing and magnitude errors at all resolutions could jeopardize accurate prediction of fire danger.
Coastal Boundary Layer Influence on Pollutant Transport in New England
Authors: Angevine Wayne M. , Senff Christoph J. , White Allen B. , Williams Eric J. , Koermer James , Miller Samuel T. K. , Talbot Robert , Johnston Paul E. , McKeen Stuart A. , Downs Tom
Published: November 2004

Air pollution episodes in northern New England often are caused by transport of pollutants over water. Two such episodes in the summer of 2002 are examined (22–23 July and 11–14 August). In both cases, the pollutants that affected coastal New Hampshire and coastal southwest Maine were transported over coastal waters in stable layers at the surface. These layers were at least intermittently turbulent but retained their chemical constituents. The lack of deposition or deep vertical mixing on the overwater trajectories allowed pollutant concentrations to remain strong. The polluted plumes came directly from the Boston, Massachusetts, area. In the 22–23 July case, the trajectories were relatively straight and dominated by synoptic-scale effects, transporting pollution to the Maine coast. On 11–14 August, sea breezes brought polluted air from the coastal waters inland into New Hampshire.
Full-Spectrum Correlated-k Distribution for Shortwave Atmospheric Radiative Transfer
Authors: Pawlak Daniel T. , Clothiaux Eugene E. , Modest Michael F. , Cole Jason N. S.
Published: November 2004

The full-spectrum correlated k-distribution (FSCK) method, originally developed for applications in combustion systems, is adapted for use in shortwave atmospheric radiative transfer. By weighting k distributions by the solar source function, the FSCK method eliminates the requirement that the Planck function be constant over a spectral interval. As a consequence, integration may be carried out across the full spectrum as long as the assumption of correlation from one atmospheric level to the next remains valid. Problems with the lack of correlation across the full spectrum are removed by partitioning the spectrum at a wavelength of 0.68 μm into two bands. The resulting two-band approach in the FSCK formalism produces broadband rms clear-sky flux and heating rate errors less than 1% and 6%, respectively, relative to monochromatic calculations and requires only 15 quadrature points per layer, which represents a 60%–90% reduction in computation time relative to other models currently in use.

An evaluation of fluxes calculated by the FSCK method in cases with idealized clouds demonstrates that gray cloud scattering in two spectral bands is sufficient to reproduce line-by-line generated fluxes. Two different approaches for modeling absorption by cloud drops were also examined. Explicitly including nongray cloud absorption in solar source function-weighted k distributions results in realistic in-cloud heating rates, although in-cloud heating rates were underpredicted by approximately 8%–12% as compared to line-by-line results. A gray cloud absorption parameter chosen to fit line-by-line results optimally for one cloud or atmospheric profile but applied to different cloud combinations or profiles, also closely approximated line-by-line heating rates.
Marine Atmospheric Boundary Layer Height over the Eastern Pacific: Data Analysis and Model Evaluation
Authors: Zeng Xubin , Brunke Michael A. , Zhou Mingyu , Fairall Chris , Bond Nicholas A. , Lenschow Donald H.
Published: November 2004

The atmospheric boundary layer (ABL) height (h) is a crucial parameter for the treatment of the ABL in weather and climate models. About 1000 soundings from 11 cruises between 1995 and 2001 over the eastern Pacific have been analyzed to document the large meridional, zonal, seasonal, and interannual variations of h. In particular, its latitudinal distribution in August has three minima: near the equator, in the intertropical convergence zone (ITCZ), and over the subtropical stratus/stratocumulus region near the west coast of California and Mexico. The seasonal peak of h in the ITCZ zone (between 5.6° and 11.2°N) occurs in the spring (February or April), while it occurs in August between the equator and 5.6°N.

Comparison of these data with the 10-yr monthly output of the Community Climate System Model (CCSM2) reveals that overall the model underestimates h, particularly north of 20°N in August and September. Directly applying the radiosonde data to the CCSM2 formulation for computing h shows that, at the original vertical resolution (with the lowest five layers below 2.1 km), the CCSM2 formulation would significantly underestimate h. In particular, the correlation coefficient between the computed and observed h values is only 0.06 for cloudy cases. If the model resolution were doubled below 2.1 km, however, the performance of the model formulation would be significantly improved with a correlation coefficient of 0.78 for cloudy cases.
An Evaluation of Mass Flux Closures for Diurnal Cycles of Shallow Cumulus
Authors: Neggers R. A. J. , Siebesma A. P. , Lenderink G. , Holtslag A. A. M.
Published: November 2004

Three closure methods for the mass flux at cloud base in shallow cumulus convection are critically examined for the difficult case of a diurnal cycle over land. The closure methods are first evaluated against large-eddy simulations (LESs) by diagnosing all parameters appearing in the closure equations during simulations of two different observed diurnal cycles of shallow cumulus. This reveals the characteristic behavior of each closure mechanism purely as a result of its core structure. With these results in hand the impact of each closure on the development of the cloudy boundary layer is then studied by its implementation in an offline single-column model of a regional atmospheric climate model. The LES results show that the boundary layer quasi-equilibrium closure typically overestimates the cloud-base mass flux after cloud onset, due to the neglect of significant moisture and temperature tendencies in the subcloud layer. The convective available potential energy (CAPE) adjustment closure is compromised by its limitation to compensating subsidence as the only CAPE breakdown mechanism and the use of a constant adjustment time scale. The closure method using the subcloud convective vertical velocity scale gives the best results, as it catches the time development of the cloud-base mass flux as diagnosed in LES.
Determination of Forecast Errors Arising from Different Components of Model Physics and Dynamics
Authors: Krishnamurti T. N. , Sanjay J. , Mitra A. K. , Vijaya Kumar T. S. V.
Published: November 2004

This paper addresses a procedure to extract error estimates for the physical and dynamical components of a forecast model. This is a two-step process in which contributions to the forecast tendencies from individual terms of the model equations are first determined using an elaborate bookkeeping of the forecast. The second step regresses these estimates of tendencies from individual terms of the model equations against the observed total tendencies. This process is executed separately for the entire horizontal and vertical transform grid points of a global model. The summary of results based on the corrections to the physics and dynamics provided by the regression coefficients highlights the component errors of the model arising from its formulation. This study provides information on geographical and vertical distribution of forecast errors contributed by features such as nonlinear advective dynamics, the rest of the dynamics, deep cumulus convection, large-scale condensation physics, radiative processes, and the rest of physics. Several future possibilities from this work are also discussed in this paper.
Precipitation Uncertainty Due to Variations in Precipitation Particle Parameters within a Simple Microphysics Scheme
Authors: Gilmore Matthew S. , Straka Jerry M. , Rasmussen Erik N.
Published: November 2004

This work reports on the sensitivity of accumulated precipitation to the microphysical parameterization in simulations of deep convective storms using a three-dimensional, nonhydrostatic cloud model with a simple liquid–ice microphysics scheme. Various intercept parameters from an assumed Marshall–Palmer exponential size distribution are tested along with two particle densities for the hail/graupel (qh) category. These variations allow testing of unique qh distributions that have been observed and documented in previous literature. Tests are conducted for a single thermodynamic profile and three idealized wind shear profiles.

The amount of accumulated precipitation at the ground is very sensitive to the way the qh category is parameterized. Distributions characterized by larger intercepts and/or smaller particle density have a smaller mass-weighted mean terminal fall velocity and produce smaller qh mixing ratios spread over a larger area. For example, for a qh category weighted toward graupel, only a fourth as much precipitation accumulates on the ground over 2 h (and none is hail) compared to a qh category weighted toward large hail (with baseball-sized stones common).

The inherent uncertainty within the qh distribution for this simple cloud-scale three-class ice microphysics scheme suggests limited usefulness in the forecasting of ground-accumulated precipitation and damaging hail.
The Boreal-Summer Intraseasonal Oscillations Simulated in a Hybrid Coupled Atmosphere–Ocean Model*
Authors: Fu Xiouhua , Wang Bin
Published: November 2004

The boreal-summer intraseasonal oscillation (BSISO) simulated by an atmosphere–ocean coupled model is validated with the long-term observations [Climate Prediction Center (CPC) Merged Analysis of Precipitation (CMAP) rainfall, ECMWF analysis, and Reynolds' SST]. This validation focuses on the three-dimensional water vapor cycle associated with the BSISO and its interaction with underlying sea surface. The advantages of a coupled approach over stand-alone atmospheric approaches on the simulation of the BSISO are revealed through an intercomparison between a coupled run and two atmosphere-only runs.

This coupled model produces a BSISO that mimics the one presented in the observations over the Asia– western Pacific region. The similarities with the observations include 1) the coherent spatiotemporal evolutions of rainfall, surface winds, and SST associated with the BSISO; 2) the intensity and period (or speed) of the northward-propagating BSISO; and 3) the tropospheric moistening (or drying) and overturning circulations of the BSISO. However, the simulated tropospheric moisture fluctuations in the extreme phases (both wet and dry) are larger than those in the ECMWF analysis. The simulated sea surface cooling during the wet phase is weaker than the observed cooling. Better representations of the interaction between convection and boundary layer in the GCM and including salinity effects in the ocean model are expected to further improve the simulation of the BSISO.

The intercomparison between a coupled run and two atmospheric runs suggests that the air–sea coupled system is the ultimate tool needed to realistically simulate the BSISO. Though the major characteristics of the BSISO are very likely determined by the internal atmospheric dynamics, the correct interaction between the internal dynamics and underlying sea surface can only be sustained by a coupled system. The atmosphere-only approach, when forced with high-frequency (e.g., daily) SST, introduces an erroneous boundary interference on the internal dynamics associated with the BSISO. The implications for the predictability of the BSISO are discussed.
A Case Study of a Chaco Low-Level Jet Event
Authors: Saulo A. Celeste , Seluchi Marcelo E. , Nicolini Matilde
Published: November 2004

This paper concentrates on the analysis of the life cycle of the low-level jet (LLJ) during a summer Chaco jet event. This is accomplished through the use of the Eta/Centro de Previsão del Tempo e Estudos Climáticos (CPTEC) regional model, in order to obtain high temporal and spatial detail of the main processes taking place. Both the low-level circulation and the geopotential height evolution at different latitudes are analyzed to provide a more detailed description of the effects of topography and differential warming on the evolution of this current.

This study shows that the life cycle of the particular event analyzed is not the same at the different latitudes swept by this well-organized northerly current, expanding from 15° to 32°S during two consecutive days. A common feature to all the examined latitudes is the presence of a diurnal cycle linked to local effects, which is more evident during the first day and a half of the simulation. This cycle was identified not only by a nocturnal maximum of the wind, but also by the oscillations of the geostrophic wind close to the surface in response to differential warming over sloping terrain. However, during the second day, the diurnal oscillation is superseded by synoptic-scale forcing. The meridional growth of this northerly current reacts basically to a deepening of the northwestern Argentinean low, consequently becoming a geostrophic response to a synoptic perturbance. However, during the final stages of this event, a northerly wind area located over the southern tip of the current, which notably increases the northerlies' penetration toward higher latitudes, develops. This last extension is mainly due to a component of ageostrophic origin. Evidence is provided in support of the hypothesis that this secondary development is a feedback between the LLJ and the precipitation at the exit region.
Formal Mentoring Programs in Education and Other Professions: A Review of the Literature
Authors: Ehrich Lisa C. , Hansford Brian , Tennent Lee
Published: November 2004

The sheer volume of literature on mentoring across a variety of disciplines is an indication of the high profile it has been afforded in recent years. This article draws on a structured analysis of more than 300 research-based articles on mentoring across three discipline areas in an attempt to make more valid inferences about the nature and outcomes of mentoring. It begins by reporting on the findings compiled from a database of research articles from educational contexts. These research-based articles are examined to determine the positive and more problematic outcomes of mentoring for the mentor, mentee, and the organization. A discussion of the findings from two other databases, namely, 151 research-based articles from business contexts and 82 articles from medical contexts, is provided, and commonalities across the three databases are highlighted. The article concludes with a discussion of key issues that administrators responsible for establishing mentoring programs should consider to maximize the experience of mentoring for all stakeholders.
Person-Job Fit Applied to Teamwork
Authors: Molleman Eric , Nauta Aukje , Jehn Karen A.
Published: November 2004

This study examined the moderating role of team task autonomy on the relationship between the mean level of three personality traits in a team—conscientiousness, emotional stability, and openness to experience—and two individual outcomes—job satisfaction and learning. Questionnaire data were collected from 133 task groups of undergraduate business students. Multilevel analyses showed that team task autonomy strengthens the relationship between conscientiousness and learning and the relationship between openness to experience and satisfaction. We conclude that team attributes, characteristics of the individual member, and team task autonomy as a moderator variable explain differences in individual outcomes and help in predicting the effectiveness of teamwork.
Blockade of α6 integrin inhibits IL-1β- but not TNF-α-induced neutrophil transmigration in vivo
Authors: Dangerfield John P , Wang Shijun , Nourshargh Sussan
Published: November 2004

In vitro and in vivo evidence supports a functional role for the integrin α6β1 in neutrophil migration through the perivascular basement membrane, a response that in vivo appears to be associated with platelet/endothelial cell adhesion molecule-1 (PECAM-1)-mediated up-regulation of α6β1 on the cell surface of transmigrating leukocytes. As the involvement of PECAM-1 in leukocyte migration is cytokine-specific, the aim of the present study was to investigate whether α6β1 exhibited a similar profile of stimulus specificity in this context. The cytokines interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) were used to elicit neutrophil migration in two murine models of inflammation, migration through cremasteric venules, as observed by intravital microscopy, and migration into the peritoneal cavity. The role of α6β1 was investigated using an α6 integrin-blocking monoclonal antibody GoH3. In both models, GoH3 significantly inhibited neutrophil transmigration induced by IL-1β but not TNF-α. This cytokine-specific role of α6 integrin was associated with enhanced cell-surface expression of α6β1 on transmigrated neutrophils (as compared with blood cells) in response to IL-1β but not TNF-α. Using lipopolysaccharide as an inflammatory stimulus in the cremaster muscle model, the study also provides evidence for the involvement of α6 integrin in leukocyte transmigration as mediated by endogenously generated IL-1β. Collectively, the findings demonstrate that α6β1 blockade inhibits neutrophil migration induced by exogenous and endogenous IL-1β but not TNF-α, observations that are associated with increased expression of the integrin on transmigrated leukocytes.
A Possible Genetic Mechanism Underlying Individual and Interstrain Differences in Opioid Actions: Focus on the Mu Opioid Receptor Gene
Authors: HAN WENHUA , IDE SOICHIRO , SORA ICHIRO , YAMAMOTO HIDEKO , IKEDA KAZUTAKA
Published: November 2004

Abstract: Individual differences in responses to opioids limit effective pain treatment with these drugs. Identifying the mechanism could help to improve the analgesic effects of them. Since the molecular cloning of the mu opioid receptor (muOR) gene, substantial advances in opioid research have been made, including the discoveries that muOR plays a mandatory role in the analgesic effects of opioids and that the sequence of the muOR gene varies from one individual to another. It is conceivable that the differences in the muOR gene cause individual differences in opioid actions. The present review summarizes the recent advances made in research on human and mouse muOR genes and proposes that the variances in the 3′ untranslated region (39‐UTR) of the muOR gene might participate in the variability of the opioid response.
Involvement of Glial Glutamate Transporters in Morphine Dependence
Authors: NAKAGAWA TAKAYUKI , SATOH MASAMICHI
Published: November 2004

Abstract: There are several lines of evidence implying the involvement of the central glutamatergic system in morphine dependence. Extracellular glutamate released from nerve terminals is counterbalanced by glutamate transporters in neurons (EAAC1 and EAAT4) and glial cells (GLT‐1 and GLAST), thereby modulating the glutamatergic system and protecting neurons from an excitotoxic action of glutamate. Here we show that a glial glutamate transporter GLT‐1 could be involved in physical and psychological morphine dependence. By Northern blot analysis, the expression of glial glutamate transporter GLT‐1, but not GLAST, mRNA was decreased in the striatum/nucleus accumbens (NAc) and thalamus of morphine‐dependent rats. Subcutaneous administration of a glutamate transporter activator suppressed the development of physical morphine dependence and morphine‐induced conditioned place preference. Intracerebroventricular administration of a glutamate transporter inhibitor to morphine‐dependent rats facilitated the expression of naloxone‐precipitated morphine withdrawal‐induced somatic signs and conditioned place aversion. Furthermore, gene transfer techniques using recombinant adenoviruses revealed that GLT‐1 in the locus coeruleus and NAc shell plays inhibitory roles in physical and psychological morphine dependence, respectively. These findings may provide evidence that a glial glutamate transporter GLT‐1 could be a new target for preventing physical and psychological morphine dependence.
Association Studies of Neurotransmitter Gene Polymorphisms in Alcoholic Caucasians
Authors: FOLEY P F , LOH E W , INNES D J , WILLIAMS S M , TANNENBERG A E G , HARPER C G , DODD P R
Published: November 2004

Abstract:Ethanol enhances mesolimbic/cortical dopamine activity in reward and reinforcement circuits. We investigated the hypothesis that risk for alcoholism may be mediated by genes for neurotransmitters associated with the dopamine reward system as well as genes for enzymes involved in ethanol metabolism. DNA was extracted from brain tissue collected at autopsy from pathologically characterized alcoholics and controls. PCR‐based assays showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2)TaqIB (P= .029) and the GABAA‐β2 subunit C1412T (P= .012) genes, but not with the glutamate receptor subunit gene NMDAR2B (366C/G), the serotonin transporter gene (5HTTL‐PR), the dopamine transporter gene DAT1(SLC6A3), the dopamine D2 receptor gene DRD2TaqIA, or the GABAAα1(A15G), α6(T1519C), and γ2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (P= .048). The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P= .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P= .047), GABAA‐β2 1412C/C (P= .01), or EAAT2 603G/A (P= .022) genotypes. Combined DRD2TaqIA or B with GABAA‐β2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism.
Profiling of Methamphetamine‐Induced Modifications of Gene Expression Patterns in the Mouse Brain
Authors: FUNADA M , ZHOU X , SATOH M , WADA K
Published: November 2004

Abstract: Recently described DNA microarray technology allows parallel screening of expression patterns and regulation of hundreds of thousands of genes. In the present study, we used a microarray to examine the gene expressions in the midbrains of mice sacrificed 24 h after completion of a 7‐day treatment period consisting of a once‐daily treatment with saline (SS), saline followed by a single 2 mg/kg of body weight dose of methamphetamine (METH) (S‐METH), or repeated 2 mg/kg METH doses (M‐METH) that produced sensitization and place preference (rewarding effect). We used the commercially available cDNA microarray. Approximately 80% of the assessed transcripts in the total brain reached the Affymetrix criteria for “present” and “changed,” as well as displaying ≥1.5‐fold differences in hybridization intensity difference values in a comparison of SS data to S‐METH or M‐METH data. S‐METH gene expression changes were observed in both up‐ and down‐regulation, with 13 transcripts upregulated and 13 downregulated, whereas the majority of M‐METH gene expression changes were observed in down‐regulation, with 5 transcripts upregulated and 21 downregulated. We identified several genes that altered expression in both the S‐METH and M‐METH groups: a transcription factor gene, cellular stress/molecular chaperones, and a cellular regulatory gene.
Similarities between Methamphetamine Toxicity and Proteasome Inhibition
Authors: FORNAI F , LENZI P , GESI M , FERRUCCI M , LAZZERI G , CAPOBIANCO L , de BLASI A , BATTAGLIA G , NICOLETTI F , RUGGIERI S , PAPARELLI A
Published: November 2004

Abstract: The monoamine neurotoxin methamphetamine (METH) is commonly used as an experimental model for Parkinson's disease (PD). In fact, METH‐induced striatal dopamine (DA) loss is accompanied by damage to striatal nerve endings arising from the substantia nigra. On the other hand, PD is characterized by neuronal inclusions within nigral DA neurons. These inclusions contain a‐synuclein, ubiquitin, and various components of a metabolic pathway named the ubiquitin‐proteasome (UP) system, while mutation of genes coding for various components of the UP system is responsible for inherited forms of PD. In this presentation we demonstrate for the first time the occurrence of neuronal inclusions in vivo in the nigrostriatal system of the mouse following administration of METH. We analyzed, in vivo and in vitro, the shape and the fine structure of these neuronal bodies by using transmission electron microscopy. Immunocytochemical investigation showed that these METH‐induced cytosolic inclusions stain for ubiquitin, a‐synuclein, and UP‐related molecules, thus sharing similar components with Lewy bodies occurring in PD, with an emphasis on enzymes belonging to the UP system. In line with this, blockade of this multicatalytic pathway by the selective inhibitor epoxomycin produced cell inclusions with similar features. Moreover, using a multifaceted pharmacological approach, we could demonstrate the need for endogenous DA in order to form neuronal inclusions.
Effects of Repeated Low Doses of MDMA on EEG Activity and Fluoro‐Jade B Histochemistry
Authors: FORNAI F , GESI M , LENZI P , FERRUCCI M , LAZZERI G , PIZZANELLI C , PELLEGRINI A , BATTAGLIA G , RUGGIERI S , PAPARELLI A
Published: November 2004

Abstract: The psychostimulant 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) is an amphetamine derivative that is widely abused. In previous studies, depending on the animal species, neurotoxicity has been demonstrated for either serotonin (5‐HT) or/and dopamine (DA) nerve endings. These studies focused on the basal ganglia circuitry; however, in humans chronic abuse of MDMA often results in neurological symptoms that last after MDMA withdrawal and are not related to the extrapyramidal system such as electroencephalographic (EEG) abnormalities and cognitive impairment. These alterations might be due to the concomitant intake of other illicit compounds, the consequence of MDMA‐induced hyperthermia, or to a primary neurotoxicity directed to extrastriatal regions. These observations call for a more in‐depth analysis on the potential involvement of brain areas outside the basal ganglia in the toxic effects induced primarily by MDMA. In the present study, we treated C57Black mice chronically (25 days) with daily injections of MDMA (2.5 mg/kg). During treatments, mice were monitored in order to detect behavioral modifications, and epidural electrodes were installed to perform EEG recording. Behavioral data showed a sensitization as measured by locomotor activity, which related to progressive and long‐lasting EEG changes and neuronal degeneration within the hippocampus.
Pro‐ and Anti‐Addictive Neurotrophic Factors and Cytokines in Psychostimulant Addiction: Mini Review
Authors: YAMADA KIYOFUMI , NABESHIMA TOSHITAKA
Published: November 2004

Abstract: Drug addiction is defined as a chronically relapsing disorder that is characterized by compulsive drug taking, inability to limit the intake, and intense drug craving. While the positive reinforcing effects of psychostimulants such as cocaine and amphetamines depend on the mesocorticolimbic dopamine system innervating nucleus accumbens, chronic drug exposure causes stable changes in the structure and function of the brain that may underlie the long‐lived behavioral abnormalities in drug addiction. Recent evidence has suggested that various neurotrophic factors and cytokines are involved in the effects of psychomotor stimulants, suggesting that these factors play a role in drug addiction. In this article, a role of neurotrophic factors and cytokines in psychostimulant addiction is discussed.
Effects of N‐Acetyl‐l‐Cysteine on the Reduction of Brain Dopamine Transporters in Monkey Treated with Methamphetamine
Authors: HASHIMOTO KENJI , TSUKADA HIDEO , NISHIYAMA SHINGO , FUKUMOTO DAI , KAKIUCHI TAKEHAU , SHIMIZU EIJI , IYO MASAOMI
Published: November 2004

Abstract: Several lines of evidence suggest that oxidative stress might contribute to neurotoxicity in the dopaminergic nerve terminals after administration of methamphetamine (MAP). The present study undertakes to determine whether intravenous administration of N‐acetyl‐l‐cysteine (NAC), a potent antioxidant drug, could attenuate the reduction of dopamine transporter (DAT) in the striatum of monkey brain after administration of MAP. Positron emission tomography (PET) studies demonstrated that repeated administration of MAP (2 mg/kg as a salt, four times at 2‐h intervals) significantly decreased the accumulation of radioactovity in the striatum after intravenous administration of [11C]b‐CFT (for DAT). In contrast, the binding of [11C]DASB to 5‐hydroxytryptamine transporter (5‐HTT) in the monkey brain was slightly decreased after the administration of MAP, although the difference was not statistically significant. The binding of [11C]SCH 23390 to dopamine D1 receptors in the striatum was also not altered after the administration of MAP. A bolus injection of NAC (150 mg/kg, i.v.) 30 min before administration of MAP and a subsequent continuous infusion of NAC (12 mg/kg/h, i.v.) over 8.5 h significantly attenuated the reduction of DAT in the monkey striatum 3 weeks after the administration of MAP. These results suggest that NAC could attenuate the reduction of DAT in the monkey striatum after repeated administration of MAP. Therefore, it is likely that NAC would be a suitable drug for treatment of neurotoxicity on dopaminergic nerve terminals related to chronic use of MAP in humans.
The Altered Disposition of Methamphetamine in the Model of Methamphetamine‐Induced Neurotoxicity
Authors: KITAICHI KIYOYUKI , ITO YUKIKO , FUKUDA MASAYA , AOYAMA NAGISA , NAKAYAMA HIRONAO , TAKAGI KENZO , HASEGAWA TAKAAKI
Published: November 2004

Abstract: Methamphetamine (METH) is a drug of abuse, causing neurotoxic effects in mammals. Many hypotheses have been proposed to explain the underlying mechanisms of METH‐induced toxicity, based on neurochemical/neuroanatomical changes. However, the pharmacokinetic properties of METH in the METH‐induced neurotoxic model have not yet been evaluated. Thus, we investigated plasma and tissue levels of METH in the METH‐induced neurotoxic model. As a result, when METH is administered multiply (5 mg/kg 4 times at 2‐h intervals) in male Wistar rats, plasma METH levels at the third and forth injections were significantly higher than those at the first. The tissue distributions of METH in the brain as well as in the kidney were significantly decreased in the third injections, suggesting the importance of decreased transport of METH into tissues. Alternatively, one week after the establishment of METH‐induced neurotoxicity, plasma levels of METH were back to normal, although METH levels in brain microdialysates were significantly higher than those in normal animals. These results suggest that the altered pharmacokinetic properties of METH, due to the abnormal membrane transport/disposition of METH into both central and peripheral tissues, might partially affect the emergence of METH‐induced neurotoxicity.
Role of Mitochondrial Dysfunction in Neurotoxicity of MPP:+: Partial Protection of PC12 Cells by Acetyl‐l‐Carnitine
Authors: VIRMANI ASHRAF , GAETANI FRANCO , BINIENDA ZBIGNIEW , XU ALEX , DUHART HELEN , ALI SYED F.
Published: November 2004

Abstract: The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1‐methyl‐4‐phenylpyridinium (MPP+), the neurotoxic metabolite of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co‐incubation of the cells with the acetylated form of carnitine, acetyl‐l‐carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH‐evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity.