bluuebunny/crossref_metadata_2025 huggingface dataset:
Intercellular Adhesion Molecule-1–Dependent Neutrophil Adhesion to Endothelial Cells Induces Caveolae-Mediated Pulmonary Vascular Hyperpermeability
Authors: Hu Guochang , Vogel Stephen M. , Schwartz David E. , Malik Asrar B. , Minshall Richard D.
Published: May 2008

We investigated the role of caveolae in the mechanism of increased pulmonary vascular permeability and edema formation induced by the activation of polymorphonuclear neutrophils (PMNs). We observed that the increase in lung vascular permeability induced by the activation of PMNs required caveolin-1, the caveolae scaffold protein. The permeability increase induced by PMN activation was blocked in caveolin-1 knockout mice and by suppressing caveolin-1 expression in rats. The response was also dependent on
Src
phosphorylation of caveolin-1 known to activate caveolae-mediated endocytosis in endothelial cells. To address the role of PMN interaction with endothelial cells, we used an intercellular adhesion molecule (ICAM)-1 blocking monoclonal antibody. Preventing the ICAM-1–mediated PMN binding to endothelial cells abrogated
Src
phosphorylation of caveolin-1, as well as the increase in endothelial permeability. Direct ICAM-1 activation by crosslinking recapitulated these responses, suggesting that ICAM-1 activates caveolin-1 signaling responsible for caveolae-mediated endothelial hyperpermeability. Our results provide support for the novel concept that a large component of pulmonary vascular hyperpermeability induced by activation of PMNs adherent to the vessel wall is dependent on signaling via caveolin-1 and increased caveolae-mediated transcytosis. Thus, it is important to consider the role of the transendothelial vesicular permeability pathway that contributes to edema formation in developing therapeutic interventions against PMN-mediated inflammatory diseases such as acute lung injury.
Genesis of Tropical Storm Eugene (2005) from Merging Vortices Associated with ITCZ Breakdowns. Part I: Observational and Modeling Analyses
Authors: Kieu Chanh Q. , Zhang Da-Lin
Published: May 2008

Although tropical cyclogenesis occurs over all tropical warm ocean basins, the eastern Pacific appears to have the highest frequency of tropical cyclogenesis events per unit area. In this study, tropical cyclogenesis from merging mesoscale convective vortices (MCVs) associated with breakdowns of the intertropical convergence zone (ITCZ) is examined. This is achieved through a case study of the processes leading to the genesis of Tropical Storm Eugene (2005) over the eastern Pacific using the National Centers for Environmental Prediction reanalysis, satellite data, and 4-day multinested cloud-resolving simulations with the Weather Research and Forecast (WRF) model at the finest grid size of 1.33 km.

Observational analyses reveal the initiations of two MCVs on the eastern ends of the ITCZ breakdowns that occurred more than 2 days and 1000 km apart. The WRF model reproduces their different movements, intensity and size changes, and vortex–vortex interaction at nearly the right timing and location at 39 h into the integration as well as the subsequent track and intensity of the merger in association with the poleward rollup of the ITCZ. Model results show that the two MCVs are merged in a coalescence and capture mode due to their different larger-scale steering flows and sizes. As the two MCVs are being merged, the low- to midlevel potential vorticity and tangential flows increase substantially; the latter occurs more rapidly in the lower troposphere, helping initiate the wind-induced surface heat exchange process leading to the genesis of Eugene with a diameter of 400 km. Subsequently, the merger moves poleward with characters of both MCVs. The simulated tropical storm exhibits many features that are similar to a hurricane, including the warm-cored “eye” and the rotating “eyewall.” It is also shown that vertical shear associated with a midlevel easterly jet leads to the downshear tilt and the wavenumber-1 rainfall structures during the genesis stage, and the upshear generation of moist downdrafts in the vicinity of the eyewall in the minimum equivalent potential temperature layer. Based on the above results, it is concluded that the ITCZ provides a favorable environment with dynamical instability, high humidity, and background vorticity, but it is the merger of the two MCVs that is critical for the genesis of Eugene. The storm decays as it moves northwestward into an environment with increasing vertical shear, dry intrusion, and colder sea surface temperatures. The results appear to have important implications for the high frequency of development of tropical cyclones in the eastern Pacific.
Attribution of Declining Western U.S. Snowpack to Human Effects
Authors: Pierce David W. , Barnett Tim P. , Hidalgo Hugo G. , Das Tapash , Bonfils Céline , Santer Benjamin D. , Bala Govindasamy , Dettinger Michael D. , Cayan Daniel R. , Mirin Art , Wood Andrew W. , Nozawa Toru
Published: May 2008

Observations show snowpack has declined across much of the western United States over the period 1950–99. This reduction has important social and economic implications, as water retained in the snowpack from winter storms forms an important part of the hydrological cycle and water supply in the region. A formal model-based detection and attribution (D–A) study of these reductions is performed. The detection variable is the ratio of 1 April snow water equivalent (SWE) to water-year-to-date precipitation (P), chosen to reduce the effect of P variability on the results. Estimates of natural internal climate variability are obtained from 1600 years of two control simulations performed with fully coupled ocean–atmosphere climate models. Estimates of the SWE/P response to anthropogenic greenhouse gases, ozone, and some aerosols are taken from multiple-member ensembles of perturbation experiments run with two models. The D–A shows the observations and anthropogenically forced models have greater SWE/P reductions than can be explained by natural internal climate variability alone. Model-estimated effects of changes in solar and volcanic forcing likewise do not explain the SWE/P reductions. The mean model estimate is that about half of the SWE/P reductions observed in the west from 1950 to 1999 are the result of climate changes forced by anthropogenic greenhouse gases, ozone, and aerosols.
Pacific Decadal Oscillation and Sea Level Variability in the Bohai, Yellow, and East China Seas
Authors: Han Guoqi , Huang Weigen
Published: May 2008

Sea level variability off East China has been investigated based primarily on 10 years of Ocean Topography Experiment (TOPEX)/Poseidon altimetry data. The altimetric annual harmonic has a magnitude of 10 to 30 cm in amplitude and is highest in summer, agreeing well with independent tide-gauge data. After the inverse barometer effect is removed, the annual sea level cycle can be approximately accounted for by the steric height variation. Significant interannual sea level change was also observed from altimetry and tide-gauge data, with a range of ∼10 cm. The interannual and longer-term sea level variability in the altimetric data are negatively correlated (significant at the 95% confidence level) with the Pacific decadal oscillation (PDO), attributed in part to steric height change. The altimetric sea level rise rate is 0.64 cm yr−1 for the period from 1992 to 2002, consistent with the tide-gauge rate of 0.6 cm yr−1. These values are much larger than the rate of 0.24 cm yr−1 observed at the same tide gauges but for the period from 1980 to 2002, implying the sensitivity to the length of data as a result of the decadal variability. The potential role of the PDO in the interannual and longer-term sea level variability is discussed in terms of regional manifestations such as the ocean temperature and salinity and the Kuroshio transport.
A Three-Dimensional Variational Data Assimilation Scheme for the Regional Ocean Modeling System
Authors: Li Zhijin , Chao Yi , McWilliams James C. , Ide Kayo
Published: May 2008

A three-dimensional variational data assimilation (3DVAR) scheme has been developed within the framework of the Regional Ocean Modeling System (ROMS). This ROMS3DVAR enables the capability of predicting meso- to small-scale variations with temporal scales from hours to days in coastal oceans. To cope with particular difficulties that result from complex coastlines and bottom topography, unbalanced flows, and sparse observations, ROMS3DVAR includes novel strategies. These strategies include the implementation of three-dimensional anisotropic and inhomogeneous error correlations based on a Kronecker product, application of particular weak dynamic constraints, and implementation of efficient and reliable algorithms for minimizing the cost function. The formulation of ROMS3DVAR is presented here, and its implementation off the West Coast is currently under way.
Simulation of Synoptic- and Subsynoptic-Scale Phenomena Associated with the East Asian Summer Monsoon Using a High-Resolution GCM
Authors: Lau Ngar-Cheung , Ploshay Jeffrey J.
Published: May 2008

A 20-yr simulation using a global atmospheric general circulation model with a resolution of 0.5° latitude × 0.625° longitude is compared with observational findings. The primary goal of this survey is to assess the model performance in reproducing various summertime phenomena related to the continental-scale Asian monsoon in general, and the regional-scale East Asian monsoon in particular. In both model and observed atmospheres, the seasonal march of the precipitation centers associated with the Asian summer monsoon is characterized by onsets occurring earliest over the southeastern Bay of Bengal, followed by rapid northeastward advances over Indochina, the South China Sea–Philippine Sea and the western Pacific, northward evolution in the East Asian sector, as well as northwestward development over the Bay of Bengal, the Indian subcontinent, and the Arabian Sea. This onset sequence is accompanied by southwesterly low-level flows over the rainy regions, as well as northwestward migration of the 200-mb Tibetan anticyclone. Analysis of the heat sources and sinks in various regions illustrates the prominent role of condensational heating in the local energy budget during the mature phases of monsoon development. In accord with observations, the simulated monsoon rains in the East Asian sector are organized about zonally elongated “mei-yu–baiu” (plum rain) systems. These precipitation features advance to higher latitudes during the June–July period, in conjunction with displacements of the axis of the low-level anticyclone over the subtropical western Pacific. A detailed case study is performed on a prominent rainy episode in the simulation. The model is capable of reproducing the observed intense gradients in temperature, humidity, and moist static stability in the vicinity of the mei-yu–baiu front, as well as the spatial relationships between the rainband and the three-dimensional flow field. The axis of the mei-yu–baiu rainband in this event is aligned with the trajectory of a succession of mesoscale cyclonic vortices, which originate from southwestern China and travel northeastward over the Yangtze River basin.
Obstacles to High-Dimensional Particle Filtering
Authors: Snyder Chris , Bengtsson Thomas , Bickel Peter , Anderson Jeff
Published: May 2008

Particle filters are ensemble-based assimilation schemes that, unlike the ensemble Kalman filter, employ a fully nonlinear and non-Gaussian analysis step to compute the probability distribution function (pdf) of a system’s state conditioned on a set of observations. Evidence is provided that the ensemble size required for a successful particle filter scales exponentially with the problem size. For the simple example in which each component of the state vector is independent, Gaussian, and of unit variance and the observations are of each state component separately with independent, Gaussian errors, simulations indicate that the required ensemble size scales exponentially with the state dimension. In this example, the particle filter requires at least 1011 members when applied to a 200-dimensional state. Asymptotic results, following the work of Bengtsson, Bickel, and collaborators, are provided for two cases: one in which each prior state component is independent and identically distributed, and one in which both the prior pdf and the observation errors are Gaussian. The asymptotic theory reveals that, in both cases, the required ensemble size scales exponentially with the variance of the observation log likelihood rather than with the state dimension per se.
A Study in Weather Model Output Postprocessing: Using the Boosting Method for Thunderstorm Detection
Authors: Perler Donat , Marchand Oliver
Published: May 2008

In this work, a new approach to weather model output postprocessing is presented. The adaptive boosting algorithm is used to train a set of simple base classifiers with historical data from weather model output, surface synoptic observation (SYNOP) messages, and lightning data. The resulting overall method then can be used to classify weather model output to identify potential thunderstorms. The method generates a certainty measure between −1 and 1, describing how likely a thunderstorm is to occur. Using a threshold, the measure can be converted to a binary decision. When compared to a linear discriminant and a method currently employed in an expert system from the German Weather Service, boosting achieves the best validation scores. A substantial improvement of the probability of detection of up to 72% and a decrease of the false alarm rate down to 34% can be achieved for the identification of thunderstorms in model analysis. Independent of the verification results, the method has several useful properties: good cross-validation results, short learning time (≤10 min sequential run time for the experiments on a standard PC), comprehensible inner values of the underlying statistical analysis, and the simplicity of adding predictors to a running system. This paper concludes with a set of possible other applications and extensions to the presented example of thunderstorm detection.
Judaism and the Origins of Erich Fromm's Humanistic Psychology
Authors: Schimmel Noam
Published: May 2008

This article explores the Jewish roots of Erich Fromm's humanistic psychology: its ethical values, conception of human nature, and societal aspirations. It analyzes key concepts in Fromm's humanistic psychology that have Jewish antecedents, including biophilia, the rejection of idolatry and group narcissism, moral universalism, and free will. It explicates Fromm's major work addressing Judaism and humanistic psychology, You Shall Be as Gods: A Radical Interpretation of the Old Testament and its Tradition, along with other texts written by Fromm that address Judaism and interpret it with a secular, humanistic orientation. The article examines how Fromm situates the Bible, the Talmud, and various rabbinic texts in relation to the development of Jewish civilization, its liberal humanistic philosophy, and the universal relevance of these texts and the values that they transmit.
A Tale of Two Bureaucrats
Authors: White Richard D.
Published: May 2008

An examination of the careers of two of George Washington's early bureaucrats— Joseph Nourse and Oliver Wolcott—deepens our understanding of the evolution of the American bureaucratic state and its mix of career employees and political appointees. In a career spanning 52 years, Nourse, the first register of the treasury, resembles the nonpartisan merit-based civil servant who spends an entire career in public service. Wolcott, the treasury's first auditor, resembles today's political appointee whose stay in government is temporary and who enters and leaves government according to the political winds. Nourse, Wolcott, and their colleagues proved to be efficient, honest, and set high standards for today's civil servants to emulate, although they stooped to the lower ethics of the time that allowed nepotism, spoilsmanship, and stock jobbery.
Broadcasting Major League Baseball as a Governmental Instrument in South Korea
Authors: Cho Younghan
Published: May 2008

This study investigates governmentality in the relationships between local governments and global sports by examining the contexts of broadcasting Major League Baseball (MLB) in South Korea. Compared to how the Korean Baseball League (KBO) was used in the 1980s to divert public interest from political issues and encourage state nationalism, the sensational popularity of MLB in the 1990s helped construct alternative governmentality during the International Monetary Fund intervention. This new governmentality not only legitimated global competition but also emphasized responsible individuals and a new kind of citizen. Rather than arguing either total failure or success of the governmentality of the 1990s, this study suggests that individuated nationalism was its consequence, meaning that most Koreans remained deeply involved with nationalistic discourse but responded to it in different and diverse ways.
Analysis of 25 Years of Technology Research as Reported in Two Professional Journals: Journal of Family and Consumer Sciences and Family and Consumer Sciences Research Journal
Authors: Leahy Amy J. , Crecelius Kayla M.
Published: May 2008

During the past 25 years, the evaluation and exploration of technological advances within family and consumer sciences (FCS) have played a vital role in the evolution of the discipline. The goal of this investigation was to provide an historical perspective of the reporting of technology or technological innovations within the field of FCS. Titles of articles published in the Journal of Family and Consumer Sciences and the Family and Consumer Sciences Research Journal as well as theses and dissertations completed as listed in the Family and Consumer Sciences Research Journal were examined from 1982 to 2007. Items were included in this analysis if technology or technological content was included in the title. This study provides an analysis of various areas of interest, including geographic location of the author, FCS area, and individual focus or topic of the article, theses, or dissertation.
Modeling the Scholarship of Teaching Through Four Family Policy Assignments
Authors: Adams Rebecca A. , McFadden Joan R.
Published: May 2008

This article describes the scholarship of teaching and discusses how it can be used in a family policy class. An Internet scavenger hunt, the use of weekly news articles for discussing family policy, a field trip to the state capitol, and a research project are the assignments described. Each assignment is followed by a discussion on how content, process, and premise reflections, components of the scholarship of teaching, can be used to evaluate and refine student achievement as well as the teacher's effectiveness skills. Rubrics for evaluating the assignments are included in the appendices. This article is designed to be helpful to faculty who teach family policy and may be adapted by other teaching professionals for a variety of disciplines.
Sμ mutation patterns suggest different progression pathways in follicular lymphoma: early direct or late from FL progenitor cells
Authors: Ruminy Philippe , Jardin Fabrice , Picquenot Jean-Michel , Parmentier Françoise , Contentin Nathalie , Buchonnet Gérard , Tison Sandrine , Rainville Vinciane , Tilly Hervé , Bastard Christian
Published: May 2008

Follicular lymphoma (FL) is a B-cell malignancy characterized by the t(14;18) translocation. Although sensitive to treatment, the disease remains incurable and the reason why tumor cells invariably evade treatment, leading to clinical relapse, is still unknown. Here, we tracked the clonal history of tumor cells by studying mutations introduced by activation-induced cytidine deaminase on the switch μ region of the der(14)t(14;18) during the early phase of the class-switch recombination (CSR) process. We observed frequent intraclonal variations, suggesting that CSR often remains active after the acquisition of the fully transformed phenotype. However, mutations only rarely accumulated over time, but instead showed complex evolutionary scenarios and 2 different progression pathways. The first pathway was a direct and rapid evolution from the dominant clone. The second was indirect, arising from earlier subclones usually after years of remission. A better understanding of these mechanisms might influence the future choice of treatment strategies.
CC chemokine receptor 5 gene promoter activation by the cyclic AMP response element binding transcription factor
Authors: Kuipers Hedwich F. , Biesta Paula J. , Montagne Lisette J. , van Haastert Elise S. , van der Valk Paul , van den Elsen Peter J.
Published: May 2008

The chemokine receptor CCR5 is implicated in the pathogenesis of various inflammatory diseases, such as multiple sclerosis (MS), atherosclerosis, transplant rejection, and autoimmunity. In previous studies, we have shown that MS lesions are characterized by enhanced expression of transcription factors associated with stress responses, ie, IRF-1, NF-κB, and CREB-1, which modulate expression of both classes of major histocompatibility complex (MHC) molecules. The expression of MHC-I and MHC-II molecules greatly overlaps with the expression of CCR5 in MS lesions. Therefore, we investigated whether these factors are also involved in the transcriptional regulation of CCR5. Using in vitro assays, we determined that neither IRF-1 nor NF-κB is involved in the activation of the CCR5 promoter. This is corroborated by the finding that these factors are not involved in the induction of endogenous CCR5 transcription in various cell types. In contrast, we show that CCR5 expression is regulated by the cAMP/CREB pathway and that interference in this pathway affects endogenous CCR5 transcription. From this, we conclude that the cAMP/CREB pathway is involved in the regulation of CCR5 transcription and that, given the ubiquitous nature of CREB-1 protein expression, additional regulatory mechanisms must contribute to cell type-specific expression of CCR5.
Genetic hitchhiking in a subdivided population of Mytilus edulis
Authors: Faure Matthieu F , David Patrice , Bonhomme François , Bierne Nicolas
Published: May 2008

Background

Few models of genetic hitchhiking in subdivided populations have been developed and the rarity of empirical examples is even more striking. We here provide evidences of genetic hitchhiking in a subdivided population of the marine mussel Mytilus edulis. In the Bay of Biscay (France), a patch of M. edulis populations happens to be separated from its North Sea conspecifics by a wide region occupied only by the sister species M. galloprovincialis. Although genetic differentiation between the two M. edulis regions is largely non-significant at ten marker loci (average FST~0.007), a strong genetic differentiation is observed at a single locus (FST = 0.25). We validated the outlier status of this locus, and analysed DNA sequence polymorphism in order to identify the nature of the selection responsible for the unusual differentiation.

Results

We first showed that introgression of M. galloprovincialis alleles was very weak in both populations and did not significantly affect their differentiation. Secondly, we observed the genetic signature of a selective sweep within both M. edulis populations in the form of a star-shaped clade of alleles. This clade was nearly fixed in the North Sea and was segregating at a moderate frequency in the Bay of Biscay, explaining their genetic differentiation. Incomplete fixation reveals that selection was not direct on the locus but that the studied sequence recombined with a positively selected allele at a linked locus while it was on its way to fixation. Finally, using a deterministic model we showed that the wave of advance of a favourable allele at a linked locus, when crossing a strong enough barrier to gene flow, generates a step in neutral allele frequencies comparable to the step observed between the two M. edulis populations at the outlier locus. In our case, the position of the barrier is now materialised by a large patch of heterospecific M. galloprovincialis populations.

Conclusion

High FST outlier loci are usually interpreted as being the consequence of ongoing divergent local adaptation. Combining models and data we show that among-population differentiation can also dramatically increase following a selective sweep in a structured population. Our study illustrates how a striking geographical pattern of neutral diversity can emerge from past indirect hitchhiking selection in a structured population.

Note

Nucleotide sequences reported in this paper are available in the GenBank™ database under the accession numbers EU684165 – EU684228.
An assessment of population structure in eight breeds of cattle using a whole genome SNP panel
Authors: McKay Stephanie D , Schnabel Robert D , Murdoch Brenda M , Matukumalli Lakshmi K , Aerts Jan , Coppieters Wouter , Crews Denny , Neto Emmanuel Dias , Gill Clare A , Gao Chuan , Mannen Hideyuki , Wang Zhiquan , Van Tassell Curt P , Williams John L , Taylor Jeremy F , Moore Stephen S
Published: May 2008

Background

Analyses of population structure and breed diversity have provided insight into the origin and evolution of cattle. Previously, these studies have used a low density of microsatellite markers, however, with the large number of single nucleotide polymorphism markers that are now available, it is possible to perform genome wide population genetic analyses in cattle. In this study, we used a high-density panel of SNP markers to examine population structure and diversity among eight cattle breeds sampled from Bos indicus and Bos taurus.

Results

Two thousand six hundred and forty one single nucleotide polymorphisms (SNPs) spanning all of the bovine autosomal genome were genotyped in Angus, Brahman, Charolais, Dutch Black and White Dairy, Holstein, Japanese Black, Limousin and Nelore cattle. Population structure was examined using the linkage model in the program STRUCTURE and Fst estimates were used to construct a neighbor-joining tree to represent the phylogenetic relationship among these breeds.

Conclusion

The whole-genome SNP panel identified several levels of population substructure in the set of examined cattle breeds. The greatest level of genetic differentiation was detected between the Bos taurus and Bos indicus breeds. When the Bos indicus breeds were excluded from the analysis, genetic differences among beef versus dairy and European versus Asian breeds were detected among the Bos taurus breeds. Exploration of the number of SNP loci required to differentiate between breeds showed that for 100 SNP loci, individuals could only be correctly clustered into breeds 50% of the time, thus a large number of SNP markers are required to replace the 30 microsatellite markers that are currently commonly used in genetic diversity studies.
Validation of oligoarrays for quantitative exploration of the transcriptome
Authors: Nygaard Vigdis , Liu Fang , Holden Marit , Kuo Winston P , Trimarchi Jeff , Ohno-Machado Lucila , Cepko Connie L , Frigessi Arnoldo , Glad Ingrid K , van de Wiel Mark A , Hovig Eivind , Lyng Heidi
Published: May 2008

Background

Oligoarrays have become an accessible technique for exploring the transcriptome, but it is presently unclear how absolute transcript data from this technique compare to the data achieved with tag-based quantitative techniques, such as massively parallel signature sequencing (MPSS) and serial analysis of gene expression (SAGE). By use of the TransCount method we calculated absolute transcript concentrations from spotted oligoarray intensities, enabling direct comparisons with tag counts obtained with MPSS and SAGE. The tag counts were converted to number of transcripts per cell by assuming that the sum of all transcripts in a single cell was 5·105. Our aim was to investigate whether the less resource demanding and more widespread oligoarray technique could provide data that were correlated to and had the same absolute scale as those obtained with MPSS and SAGE.

Results

A number of 1,777 unique transcripts were detected in common for the three technologies and served as the basis for our analyses. The correlations involving the oligoarray data were not weaker than, but, similar to the correlation between the MPSS and SAGE data, both when the entire concentration range was considered and at high concentrations. The data sets were more strongly correlated at high transcript concentrations than at low concentrations. On an absolute scale, the number of transcripts per cell and gene was generally higher based on oligoarrays than on MPSS and SAGE, and ranged from 1.6 to 9,705 for the 1,777 overlapping genes. The MPSS data were on same scale as the SAGE data, ranging from 0.5 to 3,180 (MPSS) and 9 to1,268 (SAGE) transcripts per cell and gene. The sum of all transcripts per cell for these genes was 3.8·105 (oligoarrays), 1.1·105 (MPSS) and 7.6·104 (SAGE), whereas the corresponding sum for all detected transcripts was 1.1·106 (oligoarrays), 2.8·105 (MPSS) and 3.8·105 (SAGE).

Conclusion

The oligoarrays and TransCount provide quantitative transcript concentrations that are correlated to MPSS and SAGE data, but, the absolute scale of the measurements differs across the technologies. The discrepancy questions whether the sum of all transcripts within a single cell might be higher than the number of 5·105 suggested in the literature and used to convert tag counts to transcripts per cell. If so, this may explain the apparent higher transcript detection efficiency of the oligoarrays, and has to be clarified before absolute transcript concentrations can be interchanged across the technologies. The ability to obtain transcript concentrations from oligoarrays opens up the possibility of efficient generation of universal transcript databases with low resource demands.
Excess of transmission of the G allele of the -1438A/G polymorphism of the 5-HT2Areceptor gene in patients with schizophrenia responsive to antipsychotics
Authors: Benmessaoud Dalila , Hamdani Nora , Boni Claudette , Ramoz Nicolas , Hamon Michel , Kacha Farid , Gorwood Philip
Published: May 2008

Background

The -1438A/G polymorphism of the 5-HT2Agene has been found to be associated with clinical response to clozapine and other second generation antipsychotics. Testing the impact of this marker on response to first generation antipsychotics (which have a lower affinity for the 5-HT2Areceptor) provides the opportunity to help disentangling the two different roles that this polymorphism might have. A psychopharmacogenetic role should be detected only for antipsychotics with high affinity to the 5-HT2Areceptor (therefore to second generation antipsychotics). An alternative role would imply tagging a subgroup of patients responsive to any antipsychotic, whatever their affinity, meaning that the association is more depending on non pharmacological charaterictics, such as clinical specificities.

Methods

A family-based sample of 100 Algerian patients with schizophrenia (according to DSM-IV criteria) and their 200 biological parents was recruited, in order to avoid stratification biases. Patients were all treated, or have been treated, by conventional antipsychotics (mainly haloperidol) for at least four weeks, at appropriate dosage. May and Dencker scale was used to distinguish responders and non responders.

Results

No allele of the -1438A/G polymorphism of the 5-HT2Agene was transmitted in excess (50 transmitted for 38 untransmitted) in the whole sample of patients with schizophrenia (p = .90). In contrast, a significant excess of transmission of the G allele was observed (p = .02) in the subgroup of patients with good treatment response (17 transmitted for 6 untransmitted).

Conclusion

Using a TDT approach, we showed that the G allele of the -1438A/G polymorphism of the gene coding for the 5-HT2Areceptor was associated to schizophrenia with good response to conventional antipsychotics, although this conclusion is based on 88 informative patients only. Because previous data showed the same result with atypical antipsychotics, it can be concluded that the G allele tags a subgroup of schizophrenic patients with greater chance of improvement with antipsychotics of either type.
Highly diversified multiply drug-resistant HIV-1 quasispecies in PBMCs: a case report
Authors: Quan Yudong , Brenner Bluma G , Dascal André , Wainberg Mark A
Published: May 2008

Background

Although drug resistance is a major challenge in HIV therapy, the effect of drug resistance mutations on HIV evolution in vivo is not well understood. We have now investigated genetic heterogeneity in HIV-1 by performing drug resistance genotyping of the PR-RT regions of viruses derived from plasma and peripheral blood mononuclear cells (PBMCs) of a single patient who had failed multiple regimens of anti-retroviral therapy.

Results

Patterns of drug resistance mutations showed that the viral populations in PBMCs were more heterogeneous than in plasma. Extensive analysis of HIV from infected PBMCs in this patient showed that high-level diversity existed among 109 cloned PR-RT sequences and that the majority of mutations were related to drug resistance. Moreover, the PBMCs included archival species that reflected the treatment history of the patient while those in plasma were mainly related to the most recent treatment. Some of the proviral clones contained single or multiple mutations in various combinations. Approximately eighteen percent of the proviral clones derived from infected PBMCs were defective, i.e. 5.5% contained single nucleotide deletions (frameshift mutations) and 12.8% encoded in-frame stop codons (nonsense mutations). Amino acid substitutions in PR and the polymerase region of RT occurred in 12–15% of cases but were much less frequent in the RNase H region of RT, which might not have been under drug selection pressure.

Conclusion

Selective drug pressure can yield multiple drug-resistant quasispecies that include archival and replication-incompetent species in PBMC reservoirs.
Classifying transcription factor targets and discovering relevant biological features
Authors: Holloway Dustin T , Kon Mark , DeLisi Charles
Published: May 2008

Background

An important goal in post-genomic research is discovering the network of interactions between transcription factors (TFs) and the genes they regulate. We have previously reported the development of a supervised-learning approach to TF target identification, and used it to predict targets of 104 transcription factors in yeast. We now include a new sequence conservation measure, expand our predictions to include 59 new TFs, introduce a web-server, and implement an improved ranking method to reveal the biological features contributing to regulation. The classifiers combine 8 genomic datasets covering a broad range of measurements including sequence conservation, sequence overrepresentation, gene expression, and DNA structural properties.

Principal Findings

(1) Application of the method yields an amplification of information about yeast regulators. The ratio of total targets to previously known targets is greater than 2 for 11 TFs, with several having larger gains: Ash1(4), Ino2(2.6), Yaf1(2.4), and Yap6(2.4).

(2) Many predicted targets for TFs match well with the known biology of their regulators. As a case study we discuss the regulator Swi6, presenting evidence that it may be important in the DNA damage response, and that the previously uncharacterized gene YMR279C plays a role in DNA damage response and perhaps in cell-cycle progression.

(3) A procedure based on recursive-feature-elimination is able to uncover from the large initial data sets those features that best distinguish targets for any TF, providing clues relevant to its biology. An analysis of Swi6 suggests a possible role in lipid metabolism, and more specifically in metabolism of ceramide, a bioactive lipid currently being investigated for anti-cancer properties.

(4) An analysis of global network properties highlights the transcriptional network hubs; the factors which control the most genes and the genes which are bound by the largest set of regulators. Cell-cycle and growth related regulators dominate the former; genes involved in carbon metabolism and energy generation dominate the latter.

Conclusion

Postprocessing of regulatory-classifier results can provide high quality predictions, and feature ranking strategies can deliver insight into the regulatory functions of TFs. Predictions are available at an online web-server, including the full transcriptional network, which can be analyzed using VisAnt network analysis suite.

Reviewers

This article was reviewed by Igor Jouline, Todd Mockler(nominated by Valerian Dolja), and Sandor Pongor.
Occupational allergy due to seafood delivery: Case report
Authors: Seitz Cornelia S , Bröcker Eva B , Trautmann Axel
Published: May 2008

Background

Sensitization to fish or crustaceans requires intensive skin contact and/or airway exposition and therefore especially workers in the seafood processing industry may develop an occupational seafood allergy. However, even in jobs with limited direct exposure, individuals with atopic disposition not using appropriate skin protection are at risk for developing occupational seafood allergy which requires termination of employment.

Case presentation

Due to increasing workload and pressure of time a truck driver in charge of seafood deliveries for 10 years neglected preventive measures such as wearing protective cloths and gloves which resulted in increasing direct skin contact to seafood or mucosal contact to splashing storage ice. Despite his sensitization to fish and crustaceans he tried to remain in his job but with ongoing incidental allergen exposure his symptoms progressed from initial contact urticaria to generalized urticaria, anaphylaxis and finally occupational asthma.

Conclusion

Faulty knowledge and increased work load may impede time-consuming usage of preventive measures for occupational health and safety. In predisposed atopic individuals even minor allergen exposure during seafood distribution may lead to occupational seafood allergy. With ongoing allergen exposure progression to potentially life-threatening allergy symptoms may occur.
Human papillomavirus (HPV) infection and intraepithelial neoplasia and invasive cancer of the uterine cervix: a case-control study in Zaragoza, Spain
Authors: Bernal Milagros , Burillo Isabel , Mayordomo Jose I , Moros Manuel , Benito Rafael , Gil Joaquina
Published: May 2008

Introduction

The raw incidence of cancer of the uterine cervix is Spain is 7,8 per 100.000 inhabitants (adjusted incidence is 5.6). The incidence of this tumor is still low, but a steady increase has been seen, probably related to increasing risk factors.

Aim

To determine the frequency of infection by different types of human papillomavirus (HPV) in Papanicolau smears from women with and without cancer of the uterine cervix in Spain.

Patients and methods

A case-control study was performed in women with and without cervical cancer from Zaragoza, Spain. Pap smears from 600 cases (540 women with cervical intraepithelial neoplasms (CIN) and 60 with invasive cancer) and 1200 controls (women without those lesions) were tested by polymerase chain reaction (PCR) and typed by oligonucleotide microarray-based detection.

Results

HPV was detected in 93.3% of all samples with invasive cancer versus 17.5% of controls. OR for invasive cancer was 55 (95% CI 21.5–140,5). Statistically significant associations were also found for different grades of cervical dysplasia.

Conclusion

The strong association found between HPV infection, specifically types 16 and 18 and cancer of the uterine cervix in Zaragoza, Spain, stresses the importance of ongoing efforts to institute a vaccine program with recently approved HPV vaccines in order to prevent cervical cancer in this population.
Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity
Authors: Karsdal Morten A , Madsen Suzi H , Christiansen Claus , Henriksen Kim , Fosang Amanda J , Sondergaard Bodil C
Published: May 2008

Introduction

Physiological and pathophysiological cartilage turnover may coexist in articular cartilage. The distinct enzymatic processes leading to irreversible cartilage damage, compared with those needed for continuous self-repair and regeneration, remain to be identified. We investigated the capacity of repair of chondrocytes by analyzing their ability to initiate an anabolic response subsequent to three different levels of catabolic stimulation.

Methods

Cartilage degradation was induced by oncostatin M and tumour necrosis factor in articular cartilage explants for 7, 11, or 17 days. The catabolic period was followed by 2 weeks of anabolic stimulation (insulin growth factor-I). Cartilage formation was assessed by collagen type II formation (PIINP). Cartilage degradation was measured by matrix metalloproteinase (MMP) mediated type II collagen degradation (CTX-II), and MMP and aggrecanase mediated aggrecan degradation by detecting the 342FFGVG and 374ARGSV neoepitopes. Proteoglycan turnover, content, and localization were assessed by Alcian blue.

Results

Catabolic stimulation resulted in increased levels of cartilage degradation, with maximal levels of 374ARGSV (20-fold induction), CTX-II (150-fold induction), and 342FFGVG (30-fold induction) (P < 0.01). Highly distinct protease activities were found with aggrecanase-mediated aggrecan degradation at early stages, whereas MMP-mediated aggrecan and collagen degradation occurred during later stages. Anabolic treatment increased proteoglycan content at all time points (maximally, 250%; P < 0.001). By histology, we found a complete replenishment of glycosaminoglycan at early time points and pericellular localization at an intermediate time point. In contrast, only significantly increased collagen type II formation (200%; P < 0.01) was observed at early time points.

Conclusion

Cartilage degradation was completely reversible in the presence of high levels of aggrecanase-mediated aggrecan degradation. After induction of MMP-mediated aggrecan and collagen type II degradation, the chondrocytes had impaired repair capacity.
Effects of salbutamol on exhaled breath condensate biomarkers in acute lung injury: prospective analysis
Authors: Roca Oriol , Gómez-Ollés Susana , Cruz Maria-Jesús , Muñoz Xavier , Griffiths Mark JD , Masclans Joan R
Published: May 2008

Introduction

The benefits of β-adrenergic stimulation have been described in acute lung injury (ALI), but there is still no evidence of its anti-inflammatory effect in these patients. Biomarkers in exhaled breath condensate (EBC) were used to study the effects of salbutamol on lung inflammation in mechanically ventilated patients with ALI.

Methods

EBC was collected before and 30 minutes after administration of inhaled salbutamol (800 μg). The following parameters were measured in the samples: volume obtained, conductivity, pH after helium deaeration, and concentration of nitrites, nitrates and 8-isoprostane. The leukotriene B4 concentration was measured after sample lyophilization and reconstitution. Results are expressed as the median (interquartile range).

Results

EBC was obtained from six ALI patients, with a median age of 56 (46 to 76) years. At the time of EBC collection, the Lung Injury Score was 3 (2.3 to 3.1) and the PaO2/FIO2 ratio was 133 (96 to 211) mmHg. A significant increase in deaerated EBC pH was observed after salbutamol administration (7.66 (7.58 to 7.75) versus 7.83 (7.67 to 7.91), P = 0.028). Trends toward decreased nitrosative species (18.81 (13.33 to 49.44) μM versus 21.21 (8.07 to 29.83) μM, P = 0.173) and decreased 8-isoprostane concentration (11.64 (7.17 to 17.13) pg/ml versus 6.55 (4.03 to 9.99) pg/ml, P = 0.068) were detected. No changes in leukotriene B4 concentration were found (1.58 (0.47 to 3.57) pg/ml versus 2.06 (1.01 to 3.01) pg/ml, P = 0.753).

Conclusion

EBC analysis is a noninvasive technique that can be used to monitor ventilated patients. In EBC from a small cohort of patients with ALI, inhaled salbutamol significantly decreased airspace acidosis, a marker of inflammation, and was associated with a trend toward decreased markers of nitrosative and oxidative stress.
Commensal bacteria trigger a full dendritic cell maturation program that promotes the expansion of non-Tr1 suppressor T cells
Authors: Baba Nobuyasu , Samson Sandrine , Bourdet-Sicard Raphaëlle , Rubio Manuel , Sarfati Marika
Published: May 2008

Dendritic cells (DCs) orchestrate the immune response establishing immunity versus tolerance. These two opposite functions may be dictated by DC maturation status with maturity linked to immunogenicity. DCs directly interact with trillions of noninvasive intestinal bacteria in vivo, a process that contributes to gut homeostasis. We here evaluated the maturation program elicited in human DCs by direct exposure to commensal-related bacteria (CB) in the absence of inflammatory signals. We showed that eight gram+ and gram− CB strains up-regulated costimulatory molecule expression in DCs and provoked a chemokine receptor switch similar to that activated by gram+ pathogens. CB strains may be classified into three groups according to DC cytokine release: high IL-12 and low IL-10; low IL-12 and high IL-10; and low IL-12 and IL-10. All CB-treated DCs produced IL-1β and IL-6 and almost no TGF-β. Yet, CB instructed DCs to convert naive CD4+ T cells into hyporesponsive T cells that secreted low or no IFN-γ, IL-10, and IL-17 and instead, displayed suppressor function. These data demonstrate that phenotypic DC maturation combined to an appropriate cytokine profile is insufficient to warrant Th1, IL-10-secreting T regulatory Type 1 (Tr1), or Th17 polarization. We propose that commensal flora and as such, probiotics manipulate DCs by a yet-unidentified pathway to enforce gut tolerance.
New Ways of Working and psychiatric trainees
Authors: Malik Amit , White Ollie , Mitchell Jonathan , Henderson Paul , Oakley Clare
Published: May 2008

This paper aims to consider postgraduate psychiatric training in the context of New Ways of Working for psychiatrists in England. It summarises the impact of recent changes in postgraduate training and the major training implications of New Ways of Working. Finally, it outlines some broad principles that need to be considered for training when implementing New Ways of Working locally.
Secure in-patient services for people with learning disability: is the market serving the user well?
Authors: Yacoub Evan , Hall Ian , Bernal Jane
Published: May 2008

Medium-secure care services developed in England following the Butler report (Home Office & Department of Health and Social Security, 1975). They were established to address the major gap in provision between high-secure and local mental health services. However, the development of special secure services for offenders with a learning disability has largely been neglected (Snowden, 1995). People with learning disability who require secure in-patient care are often placed in remote and costly units because suitable local facilities do not exist. Such placements do not usually accord with user and carer wishes.
John Farley: Formerly Consultant Psychiatrist, Fairfield Hospital, Hertfordshire
Authors: Weir Neville
Published: May 2008

John was born on 6 December 1925 at Harbury, Warwickshire. He developed a very early interest in cars and motorbikes; indeed, he was able to decoke a motorbike at the age of 9 and learnt to drive along country tracks at a very early age. He attended Uppingham School and also acquired an interest in Freud. He qualified MBBS at the University of London (Barts) in 1951.