bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo
Authors: Anderson Leah J. , Longnecker Richard
Published: September 2008

Expression of latent membrane protein 2 (LMP2A) during B-cell development leads to global alterations in gene transcription similar to those seen in Hodgkin Reed-Sternberg cells of Hodgkin lymphoma (HL). Along with the consistent detection of LMP2A in Epstein-Barr virus–associated HL, this implicates a role for LMP2A in the pathogenesis of HL. We have shown that LMP2A constitutively activates the Notch1 pathway to autoregulate the LMP2A promoter. To determine whether constitutive activation of the Notch pathway is important for LMP2A-mediated alterations in B-cell development in vivo, TgE-LMP2A–transgenic mice were intercrossed with mice expressing loxP-flanked Notch1 genes and Cre recombinase. B cells from TgE Notch1lox/lox-CD19+/Cre mice have an increase in immunoglobulin M and CD43 and a decrease in CD5 expression in the bone marrow compared with TgE Notch1lox/lox mice, indicating the LMP2A signal for developmental aberrations is impaired in the absence of Notch1. Real-time reverse-transcribed polymerase chain reaction analysis reveals that LMP2A requires the Notch1 pathway to alter levels of B cell–specific transcription factors, E2A and EBF. Interestingly, Notch1 appears to be important for LMP2A-mediated survival in low interleukin-7. We propose that LMP2A and the Notch1 pathway may cooperate to induce the alterations in B-cell identity seen in Hodgkin Reed-Sternberg cells.
Mesenchymal stromal cell–derived CCL2 suppresses plasma cell immunoglobulin production via STAT3 inactivation and PAX5 induction
Authors: Rafei Moutih , Hsieh Jeremy , Fortier Simon , Li MengYang , Yuan Shala , Birman Elena , Forner Kathy , Boivin Marie-Noelle , Doody Karen , Tremblay Michel , Annabi Borhane , Galipeau Jacques
Published: September 2008

We demonstrate that the secretome of mesenchymal stromal cells (MSCs) suppresses plasma cell (PC) immunoglobulin (Ig) production, induces plasmablast proliferation, and leads to interleukin-10–mediated blockade in vitro. We found that these effects are the result of MSC-derived CC chemokine ligands CCL2 and CCL7. More specifically, MSCs further processed these CC chemokines by the activity of matrix metalloproteinases (MMPs), leading to the generation of proteolytically processed antagonistic CCL2 variant. Neutralizing CCL2 or inhibiting MMP enzymatic activity abolished the PC-suppressive effect of MSCs. We also observed that MMP-processed CCL2 suppresses signal transducer and activator of transcription 3 (STAT3) activation in PC. As a result, the transcription factor PAX5 is induced, thus explaining the inhibition of Ig synthesis. The absence of inhibitory effects by MSC on the humoral response of CCR2−/− mice to xenoantigen suggests that MMP-cleaved CCL2/CCR2 interaction as well as downstream phosphatase activity is necessary for antagonistic effect. We tested syngeneic MSCs in hemophilic B6 mice with predeveloped antihuman factor VIII (hFVIII) antibodies and demonstrated a robust decrease in hFVIII-specific IgG levels. Thus, MSCs may play a role in modulating Ig production by PCs via MMP processing of CCL2 and may represent an appealing cell therapy approach for pathologic humoral responses.
GBNet: Deciphering regulatory rules in the co-regulated genes using a Gibbs sampler enhanced Bayesian network approach
Authors: Shen Li , Liu Jie , Wang Wei
Published: September 2008

Background

Combinatorial regulation of transcription factors (TFs) is important in determining the complex gene expression patterns particularly in higher organisms. Deciphering regulatory rules between cooperative TFs is a critical step towards understanding the mechanisms of combinatorial regulation.

Results

We present here a Bayesian network approach called GBNet to search for DNA motifs that may be cooperative in transcriptional regulation and the sequence constraints that these motifs may satisfy. We showed that GBNet outperformed the other available methods in the simulated and the yeast data. We also demonstrated the usefulness of GBNet on learning regulatory rules between YY1, a human TF, and its co-factors. Most of the rules learned by GBNet on YY1 and co-factors were supported by literature. In addition, a spacing constraint between YY1 and E2F was also supported by independent TF binding experiments.

Conclusion

We thus conclude that GBNet is a useful tool for deciphering the "grammar" of transcriptional regulation.
SCUD: Saccharomyces Cerevisiae Ubiquitination Database
Authors: Lee Won-Chul , Lee Minho , Jung Jin Woo , Kim Kwang Pyo , Kim Dongsup
Published: September 2008

Background

Ubiquitination is an important post-translational modification involved in diverse biological processes. Therefore, genomewide representation of the ubiquitination system for a species is important.

Description

SCUD is a web-based database for the ubiquitination system in Saccharomyces cerevisiae (Baker's yeast). We first searched for all the known enzymes involved in the ubiquitination process in yeast, including E1, E2, E3, and deubiquitination enzymes. Then, ubiquitinated substrates were collected by literature search. Especially, E3 and deubiquitination enzymes are classified into classes and subclasses by their shared domains and unique functions. As a result, 42 different E3 enzymes were grouped into corresponding classes and subclasses, and 940 ubiquitinated substrates including mutant substrates were identified. All the enzyme and substrate information are interconnected by hyperlinks, which makes it easy to view the enzyme-specific ubiquitination information.

Conclusion

This database aims to represent a comprehensive yeast ubiquitination system, and is easily expandable with the further experimental data. We expect that this database will be useful for the research on the ubiquitination systems of other higher organisms.

SCUD is accessible at http://scud.kaist.ac.kr
Evolution of the holozoan ribosome biogenesis regulon
Authors: Brown Seth J , Cole Michael D , Erives Albert J
Published: September 2008

Background

The ribosome biogenesis (RiBi) genes encode a highly-conserved eukaryotic set of nucleolar proteins involved in rRNA transcription, assembly, processing, and export from the nucleus. While the mode of regulation of this suite of genes has been studied in the yeast, Saccharomyces cerevisiae, how this gene set is coordinately regulated in the larger and more complex metazoan genomes is not understood.

Results

Here we present genome-wide analyses indicating that a distinct mode of RiBi regulation co-evolved with the E(CG)-binding, Myc:Max bHLH heterodimer complex in a stem-holozoan, the ancestor of both Metazoa and Choanoflagellata, the protozoan group most closely related to animals. These results show that this mode of regulation, characterized by an E(CG)-bearing core-promoter, is specific to almost all of the known genes involved in ribosome biogenesis in these genomes. Interestingly, this holozoan RiBi promoter signature is absent in nematode genomes, which have not only secondarily lost Myc but are marked by invariant cell lineages typically producing small body plans of 1000 somatic cells. Furthermore, a detailed analysis of 10 fungal genomes shows that this holozoan signature in RiBi genes is not found in hemiascomycete fungi, which evolved their own unique regulatory signature for the RiBi regulon.

Conclusion

These results indicate that a Myc regulon, which is activated in proliferating cells during normal development as well as during tumor progression, has primordial roots in the evolution of an inducible growth regime in a protozoan ancestor of animals. Furthermore, by comparing divergent bHLH repertoires, we conclude that regulation by Myc but not by other bHLH genes is responsible for the evolutionary maintenance of E(CG) sites across the RiBi suite of genes.
Structural analysis of FAD synthetase from Corynebacterium ammoniagenes
Authors: Frago Susana , Martínez-Júlvez Marta , Serrano Ana , Medina Milagros
Published: September 2008

Background

The prokaryotic FAD synthetase family – a group of bifunctional enzymes that catalyse riboflavin phosphorylation and FMN adenylylation within a single polypeptide chain- was analysed in terms of sequence and structure.

Results

Sequences of nearly 800 prokaryotic species were aligned. Those related with bifunctional FAD synthetase activities showed conservation of several consensus regions and highly conserved residues. A 3D model for the FAD synthetase from Corynebacterium ammoniagenes (CaFADS) was generated. This model confirms that the N-terminal and C-terminal domains are related to nucleotydyltransferases and riboflavin kinases, respectively. Models for the interaction of CaFADS with its substrates were also produced, allowing location of all the protein substrates in their putative binding pockets. These include two independent flavin binding sites for each CaFADS activity.

Conclusion

For the first time, the putative presence of a flavin binding site for the adenylylation activity, independent from that related with the phosphorylation activity, is shown. Additionally, these models suggest the functional relevance of some residues putatively involved in the catalytic processes. Their relevant roles were analysed by site-directed mutagenesis. A role was confirmed for H28, H31, S164 and T165 in the stabilisation of the P groups and the adenine moiety of ATP and, the P of FMN for the adenylylation. Similarly, T208, N210 and E268 appear critical for accommodation of the P groups of ATP and the ribityl end of RF in the active site for the phosphorylation process. Finally, the C-terminal domain was shown to catalyse the phosphorylation process on its own, but no reaction at all was observed with the individually expressed N-terminal domain.
Development of a luciferase-based reporter system to monitor Bifidobacterium breve UCC2003 persistence in mice
Authors: Cronin Michelle , Sleator Roy D , Hill Colin , Fitzgerald Gerald F , van Sinderen Douwe
Published: September 2008

Background

Probiotics such as bifidobacteria have been shown to maintain a healthy intestinal microbial balance and help protect against infections. However, despite these benefits, bifidobacteria still remain poorly understood at the biochemical, physiological and especially the genetic level. Herein we describe, for the first time, the development of a non-invasive luciferase-based reporter system for real-time tracking of Bifidobacterium species in vivo.

Results

The reporter vector pLuxMC1 is based on the recently described theta-type plasmid pBC1 from B. catenatulatum [1] and the luxABCDE operon from pPL2lux [2]. Derivatives of pLuxMC1, harbouring a bifidobacterial promoter (pLuxMC2) as well as a synthetically derived promoter (pLuxMC3) [3] placed upstream of luxABCDE, were constructed and found to stably replicate in B. breve UCC2003. The subsequent analysis of these strains allowed us to assess the functionality of pLuxMC1 both in vitro and in vivo.

Conclusion

Our results demonstrate the potential of pLuxMC1 as a real-time, non-invasive reporter system for Bifidobacterium. It has also allowed us, for the first time, to track the colonisation potential and persistence of this probiotic species in real time. An interesting and significant outcome of the study is the identification of the caecum as a niche environment for B. breve UCC2003 within the mouse gastrointestinal tract (GI) tract.
Association between regular participation in sports and leisure time behaviors in Brazilian adolescents: A cross-sectional study
Authors: Fernandes Rômulo Araújo , Júnior Ismael Forte Freitas , Cardoso Jefferson Rosa , Vaz Ronque Enio Ricardo , Loch Mathias Roberto , de Oliveira Arli Ramos
Published: September 2008

Background

The belief that adolescents engaged in sports increase their overall physical activity level while simultaneously decreasing physical inactivity has been the foundation of many intervention programs in developing countries. The aim of this study was to analyze the association between regular participation in sports and both active behaviors and TV viewing during leisure time.

Methods

A total of 1752 Brazilian adolescents (812 = male and 940 = female) participated in this study. Regular participation in sports, as well as active behaviors (exemplified by walking or cycling) and TV viewing during leisure time were assessed by means of a questionnaire. The chi-square test analyzed the association between sports practice and leisure time behaviors, and the Poisson regression with robust variance indicated the magnitude of these associations.

Results

The prevalence of regular participation in sports was 14.8% (95% confidence interval 13.2% to 16.5%). After adjustment for all confounders, participation in sports was associated with, at the highest frequency, cycling (PR = 2.55 [1.80–3.60]) and walking (PR = 2.69 [1.98–3.64]) during leisure time. However, there was not an association between the participation in sports and frequency of TV viewing (PR = 1.28 [0.81–2.02]).

Conclusion

This study presented data indicating that the regular participation in sports is positively associated with a higher frequency of physically active behaviors during leisure time. However, the results did not support the hypothesis that the engagement in sports necessarily decreases leisure time spent in TV viewing.
Viral cystatin evolution and three-dimensional structure modelling: A case of directional selection acting on a viral protein involved in a host-parasitoid interaction
Authors: Serbielle Céline , Chowdhury Shafinaz , Pichon Samuel , Dupas Stéphane , Lesobre Jérôme , Purisima Enrico O , Drezen Jean-Michel , Huguet Elisabeth
Published: September 2008

Background

In pathogens, certain genes encoding proteins that directly interact with host defences coevolve with their host and are subject to positive selection. In the lepidopteran host-wasp parasitoid system, one of the most original strategies developed by the wasps to defeat host defences is the injection of a symbiotic polydnavirus at the same time as the wasp eggs. The virus is essential for wasp parasitism success since viral gene expression alters the immune system and development of the host. As a wasp mutualist symbiont, the virus is expected to exhibit a reduction in genome complexity and evolve under wasp phyletic constraints. However, as a lepidopteran host pathogenic symbiont, the virus is likely undergoing strong selective pressures for the acquisition of new functions by gene acquisition or duplication. To understand the constraints imposed by this particular system on virus evolution, we studied a polydnavirus gene family encoding cyteine protease inhibitors of the cystatin superfamily.

Results

We show that cystatins are the first bracovirus genes proven to be subject to strong positive selection within a host-parasitoid system. A generated three-dimensional model of Cotesia congregata bracovirus cystatin 1 provides a powerful framework to position positively selected residues and reveal that they are concentrated in the vicinity of actives sites which interact with cysteine proteases directly. In addition, phylogenetic analyses reveal two different cystatin forms which evolved under different selective constraints and are characterized by independent adaptive duplication events.

Conclusion

Positive selection acts to maintain cystatin gene duplications and induces directional divergence presumably to ensure the presence of efficient and adapted cystatin forms. Directional selection has acted on key cystatin active sites, suggesting that cystatins coevolve with their host target. We can strongly suggest that cystatins constitute major virulence factors, as was already proposed in previous functional studies.
Immunity, ageing and cancer
Authors: Derhovanessian Evelyna , Solana Rafael , Larbi Anis , Pawelec Graham
Published: September 2008

Compromised immunity contributes to the decreased ability of the elderly to control infectious disease and to their generally poor response to vaccination. It is controversial as to how far this phenomenon contributes to the well-known age-associated increase in the occurrence of many cancers in the elderly. However, should the immune system be important in controlling cancer, for which there is a great deal of evidence, it is logical to propose that dysfunctional immunity in the elderly would contribute to compromised immunosurveillance and increased cancer occurrence. The chronological age at which immunosenescence becomes clinically important is known to be influenced by many factors, including the pathogen load to which individuals are exposed throughout life. It is proposed here that the cancer antigen load may have a similar effect on "immune exhaustion" and that pathogen load and tumor load may act additively to accelerate immunosenescence. Understanding how and why immune responsiveness changes in humans as they age is essential for developing strategies to prevent or restore dysregulated immunity and assure healthy longevity, clearly possible only if cancer is avoided. Here, we provide an overview of the impact of age on human immune competence, emphasizing T-cell-dependent adaptive immunity, which is the most sensitive to ageing. This knowledge will pave the way for rational interventions to maintain or restore appropriate immune function not only in the elderly but also in the cancer patient.
Impairment of the CD8+ T cell response in lungs following infection with human respiratory syncytial virus is specific to the anatomical site rather than the virus, antigen, or route of infection
Authors: DiNapoli Joshua M , Murphy Brian R , Collins Peter L , Bukreyev Alexander
Published: September 2008

Background

A subset of the virus-specific CD8+ cytotoxic T lymphocytes (CTL) isolated from the lungs of mice infected with human respiratory syncytial virus (RSV) is impaired in the ability to secrete interferon γ (IFNγ), a measure of functionality. It was suggested that the impairment specifically suppressed the host cellular immune response, a finding that could help explain the ability of RSV to re-infect throughout life.

Results

To determine whether this effect is dependent on the virus, the route of infection, or the type of infection (respiratory, disseminated, or localized dermal), we compared the CTL responses in mice following intranasal (IN) infection with RSV or influenza virus or IN or intradermal (ID) infection with vaccinia virus expressing an RSV CTL antigen. The impairment was observed in the lungs after IN infection with RSV, influenza or vaccinia virus, and after a localized ID infection with vaccinia virus. In contrast, we observed a much higher percentage of IFNγ secreting CD8+ lymphocytes in the spleens of infected mice in every case.

Conclusion

The decreased functionality of CD8+ CTL is specific to the lungs and is not dependent on the specific virus, viral antigen, or route of infection.
The Chemokine CXCL1/Growth Related Oncogene Increases Sodium Currents and Neuronal Excitability in Small Diameter Sensory Neurons
Authors: Wang Jun-Gang , Strong Judith A , Xie Wenrui , Yang Rui-Hua , Coyle Dennis E , Wick Dayna M , Dorsey Ericka D , Zhang Jun-Ming
Published: September 2008

Background:

Altered Na+ channel expression, enhanced excitability, and spontaneous activity occur in nerve-injury and inflammatory models of pathological pain, through poorly understood mechanisms. The cytokine GRO/KC (growth related oncogene; CXCL1) shows strong, rapid upregulation in dorsal root ganglion in both nerve injury and inflammatory models. Neurons and glia express its receptor (CXCR2). CXCL1 has well-known effects on immune cells, but little is known about its direct effects on neurons.

Results:

We report that GRO/KC incubation (1.5 nM, overnight) caused marked upregulation of Na+ currents in acutely isolated small diameter rat (adult) sensory neurons in vitro. In both IB4-positive and IB4-negative sensory neurons, TTX-resistant and TTX-sensitive currents increased 2-to 4 fold, without altered voltage dependence or kinetic changes. These effects required long exposures, and were completely blocked by co-incubation with protein synthesis inhibitor cycloheximide. Amplification of cDNA from the neuronal cultures showed that 3 Na channel isoforms were predominant both before and after GRO/KC treatment (Nav 1.1, 1.7, and 1.8). TTX-sensitive isoforms 1.1 and 1.7 significantly increased 2 – 3 fold after GRO/KC incubation, while 1.8 showed a trend towards increased expression. Current clamp experiments showed that GRO/KC caused a marked increase in excitability, including resting potential depolarization, decreased rheobase, and lower action potential threshold. Neurons acquired a striking ability to fire repetitively; IB4-positive cells also showed marked broadening of action potentials. Immunohistochemical labelling confirmed that the CXCR2 receptor was present in most neurons both in dissociated cells and in DRG sections, as previously shown for neurons in the CNS.

Conclusion:

Many studies on the role of chemokines in pain conditions have focused on their rapid and indirect effects on neurons, via release of inflammatory mediators from immune and glial cells. Our study suggests that GRO/KC may also have important pro-nociceptive effects via its direct actions on sensory neurons, and may induce long-term changes that involve protein synthesis.
A comparative analysis of metal transportomes from metabolically versatile Pseudomonas
Authors: Haritha Adhikarla , Rodrigue Agnes , Mohan Pamarthi Maruthi
Published: September 2008

Background

The availability of complete genome sequences of versatile Pseudomonas occupying remarkably diverse ecological niches enabled to gain insights into their adaptative assets. The objective of this study was to analyze the complete genetic repertoires of metal transporters (metal transportomes) from four representative Pseudomonas species and to identify metal transporters with "Genomic Island" associated features.

Methods

A comparative metal transporter inventory was built for the following four Pseudomonas species: P.putida (Ppu) KT2440, P.aeruginosa (Pae) PA01, P.fluorescens (Pfl) Pf-5 and P.syringae (Psy)pv.tomato DC3000 using TIGR-CMR and Transport DB. Genomic analysis of essential and toxic metal ion transporters was accomplished from the above inventory. Metal transporters with "Genomic Island" associated features were identified using Islandpath analysis.

Results

Dataset cataloguing has been executed for 262 metal transporters from the four spp. Additional metal ion transporters belonging to NiCoT, Ca P-type ATPase, Cu P-type ATPases, ZIP and MgtC families were identified. In Psy DC3000, 48% of metal transporters showed strong GI features while it was 45% in Ppu KT2440. In Pfl Pf-5 and Pae PA01 only 26% of their metal transporters exhibited GI features.

Conclusion

Our comparative inventory of 262 metal transporters from four versatile Pseudomonas spp is the complete suite of metal transportomes analysed till date in a prokaryotic genus. This study identified differences in the basic composition of metal transportomes from Pseudomonas occupying diverse ecological niches and also elucidated their novel features. Based on this inventory we analysed the role of horizontal gene transfer in expansion and variability of metal transporter families.
Reliability and accuracy of interview data in non-smoking female lung cancer case-control study
Authors: Huang Desheng , Guan Peng , Shi Hailong , He Qincheng , Zhou Baosen
Published: September 2008

Background

Valid interview data is critical to the final results of the study. The purpose of this study was to investigate the reliability of epidemiological data obtained in non-smoking female lung cancer case-control study in China.

Methods

Fifty-six pairs of cases and controls, 10% percent of all the collected subjects were re-interviewed by three interviewers who underwent identical standardized training. A limited number of questions included in the original survey were asked again, the responses from the re-interview were compared with the original interview. Kappa was calculated by negative rates of agreement, positive rates of agreement and total rates of agreement to the accordance degree between the two interviews.

Results

The Kappa values were all more than 0.5 in all the studied indexes. The Kappa values descended from 0.92 in family history of cancer to 0.56 in oral contraception use. Errors in collecting and classifying data did occur, and were especially common for complicated clinical events, such as a drug exposure occurring many years before.

Conclusion

We identified four sources of this variability, three in collecting the data, and one in coding. As a result of these findings, strategies are proposed for improving the quality of interview data obtained in epidemiological research. Before finding a good solution, the strategy of data collecting and coding should be simple and easy to inspect.
Sp1 is involved in H2O2-induced PUMA gene expression and apoptosis in colorectal cancer cells
Authors: Wang Xinying , Wang Jing , Lin Shiyong , Geng Yan , Wang Jide , Jiang Bo
Published: September 2008

Background

Reactive oxygen species (ROS) are intricately involved in tumor progression through effects on proliferation, apoptosis and metastasis. But how ROS works is not well understood. In previous study, we found PUMA (p53-upregulated modulator of apoptosis) played an important role in oxaliplatin-induced apoptosis. In the present study, we detect the role of PUMA in H2O2-induced apoptosis in colorectal cancer cells and investigate the potential mechanism.

Methods and results

We showed that H2O2 stimulated the activity of a 493 PUMA promoter reporter gene construct. Suppressing the expression of PUMA abrogated H2O2-induced apoptosis. Deletion of the Sp1-binding sites also decreased the transactivation of PUMA promoter by H2O2. Furthermore, induction of PUMA promoter activity by H2O2 was abrogated by PFT-α (a p53 inhibitor) and Mithramycin A (a Sp1 inhibitor), as compared with PFT-α alone. To determine the effects of Sp1 on PUMA in H2O2-induced apoptosis, procaspase 3, procaspase 9 and procaspase 8 expression was assessed. Mithramycin A and PFT-α also reduced H2O2-induced apoptosis synergistically and abrogated the expression of procaspase 3 and procaspase 9.

Conclusion

Our findings suggest that PUMA plays a role in H2O2-induced apoptosis, and that Sp1 works together with p53 in the regulation of H2O2-induced PUMA expression and apoptosis in colorectal cancer cells. This study provides important regulatory insights in the mechanisms of ROS in colorectal cancer.
Increases in Bone Mineral Density in Response to Oral Dehydroepiandrosterone Replacement in Older Adults Appear to Be Mediated by Serum Estrogens
Authors: Jankowski Catherine M. , Gozansky Wendolyn S. , Kittelson John M. , Van Pelt Rachael E. , Schwartz Robert S. , Kohrt Wendy M.
Published: September 2008

Context: The mechanisms by which dehydroepiandrosterone (DHEA) replacement increases bone mineral density (BMD) in older adults are not known.

Objective: The aims were to determine the effects of DHEA therapy on changes in sex hormones and IGF-I and their associations with changes in BMD.

Design, Setting, and Participants: A randomized, double-blinded, placebo-controlled trial was conducted at an academic research institution. Participants were 58 women and 61 men, aged 60–88 yr, with low serum DHEA sulfate (DHEAS) levels.

Intervention: The intervention was oral DHEA 50 mg/d or placebo for 12 months.

Main Outcome Measures: BMD and serum DHEAS, testosterone, estradiol (E2), estrone (E1), SHBG, IGF-I, and IGF binding protein 3 were measured before and after intervention. Free testosterone and estrogen (FEI) indices were calculated.

Results: The average changes in hip and spine BMD (DHEA vs. placebo) ranged from 1.1 to 1.6%. Compared with placebo, DHEA replacement increased serum DHEAS, testosterone, free testosterone index, E1, E2, FEI, and IGF-I (all P < 0.001) and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E1, FEI (all P < 0.001), and E2 (P = 0.02) and decreased SHBG (P = 0.037). The changes in total and regional hip BMD were associated with 12-month E2 (all P ≤ 0.001) and FEI (all P ≤ 0.013). The effects of DHEA treatment were eliminated by adjustment for 12-month E2.

Conclusions: The significant increases in hip BMD in older adults undergoing DHEA replacement were mediated primarily by increases in serum E2 rather than direct effects of DHEAS.
GNAS Defects Identified by Stimulatory G Protein α-Subunit Signalling Studies in Platelets
Authors: Freson Kathleen , Izzi Benedetta , Labarque Veerle , Van Helvoirt Monique , Thys Chantal , Wittevrongel Christine , Bex Marie , Bouillon Roger , Godefroid Nathalie , Proesmans Willem , de Zegher Francis , Jaeken Jaak , Van Geet Chris
Published: September 2008

Context: GNAS is an imprinted region that gives rise to several transcripts, antisense transcripts, and noncoding RNAs, including transcription of RNA encoding the α-subunit of the stimulatory G protein (Gsα). The complexity of the GNAS cluster results in ubiquitous genomic imprints, tissue-specific Gsα expression, and multiple genotype-phenotype relationships. Phenotypes resulting from genetic and epigenetic abnormalities of the GNAS region include Albright’s hereditary osteodystrophy, pseudohypoparathyroidism types Ia (PHPIa) and Ib (PHPIb), and pseudopseudohypoparathyroidism (PPHP).

Objective: The aim was to study the complex GNAS pathology by a functional test as an alternative to the generally used but labor-intensive erythrocyte complementation assay.

Design and Patients: We report the first platelet-based diagnostic test for Gsα hypofunction, supported by clinical, biochemical, and molecular data for six patients with PHPIa or PPHP and nine patients with PHPIb. The platelet test is based on the inhibition of platelet aggregation by cAMP, produced after Gsα stimulation.

Results: Platelets are easily accessible, and platelet aggregation responses were found to reflect Gsα signaling defects in patients, in concordance with the patient’s phenotype and genotype. Gsα hypofunction in PHPIa and PPHP patients with GNAS mutations was clearly detected by this method. Mildly decreased or normal Gsα function was detected in patients with PHPIb with either an overall or exon 1A-only epigenetic defect, respectively. Platelet Gsα expression was reduced in both PHPIb patient groups, whereas XLαs was up-regulated only in PHPIb patients with the broad epigenetic defect.

Conclusion: The platelet-based test is a novel tool for establishing the diagnosis of Gsα defects, which may otherwise be quite challenging.
Effects of Perilipin (PLIN) Gene Variation on Metabolic Syndrome Risk and Weight Loss in Obese Children and Adolescents
Authors: Deram Sophie , Nicolau Christiane Y. , Perez-Martinez Pablo , Guazzelli Isabel , Halpern Alfredo , Wajchenberg Bernardo L. , Ordovas Jose M. , Villares Sandra M.
Published: September 2008

Context: Genetic polymorphisms at the perilipin (PLIN) locus have been investigated for their potential utility as markers for obesity and metabolic syndrome (MS). We examined in obese children and adolescents (OCA) aged 7–14 yr the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multidisciplinary behavioral and nutritional treatment without medication.

Design: A total of 234 OCA [body mass index (BMI = 30.4 ± 4.4 kg/m2; BMI Z-score = 2.31 ± 0.4) were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1 6209T→C, PLIN4 11482G→A, PLIN5 13041A→G, and PLIN6 14995A→T).

Results: Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in linkage disequilibrium (D′ = 0.999; P < 0.001). At baseline, no anthropometric differences were observed, but minor allele A at PLIN4 was associated with higher triglycerides (111 ± 49 vs. 94 ± 42 mg/dl; P = 0.003), lower high-density lipoprotein cholesterol (40 ± 9 vs. 44 ± 10 mg/dl; P = 0.003) and higher homeostasis model assessment for insulin resistance (4.0 ± 2.3 vs. 3.5 ± 2.1; P = 0.015). Minor allele A at PLIN4 was associated with MS risk (age and sex adjusted) hazard ratio 2.4 (95% confidence interval = 1.1–4.9) for genotype GA and 3.5 (95% confidence interval = 1.2–9.9) for AA. After intervention, subjects carrying minor allele T at PLIN6 had increased weight loss (3.3 ± 3.7 vs. 1.9 ± 3.4 kg; P = 0.002) and increased loss of the BMI Z-score (0.23 ± 0.18 vs. 0.18 ± 0.15; P = 0.003). Due to group size, risk of by-chance findings cannot be excluded.

Conclusion: The minor A allele at PLIN4 was associated with higher risk of MS at baseline, whereas the PLIN6 SNP was associated with better weight loss, suggesting that these polymorphisms may predict outcome strategies based on multidisciplinary treatment for OCA.
Prevalence of Metabolic Syndrome and Related Characteristics in Obese Adolescents with and without Polycystic Ovary Syndrome
Authors: Rossi Brooke , Sukalich Sara , Droz Jennifer , Griffin Adam , Cook Stephen , Blumkin Aaron , Guzick David S. , Hoeger Kathleen M.
Published: September 2008

Context: Adults with polycystic ovary syndrome (PCOS) may be at increased risk for metabolic syndrome (MBS) and related cardiovascular disease. It is not clear whether PCOS diagnosed in adolescence increases the risk of MBS in this age group.

Objective: The aim was to compare the prevalence and related characteristics of MBS in obese adolescents with and without PCOS.

Design: We conducted a cross-sectional study of overweight and obese PCOS adolescents and BMI matched controls.

Patients and Participants: A total of 74 subjects, 43 with PCOS and 31 controls, participated in the study.

Interventions: Each subject underwent a physical examination and laboratory evaluation for a diagnosis of MBS. Regional fat distribution was determined by computerized tomography scan in the PCOS adolescents.

Main Outcome Measures: We measured the prevalence of MBS and its components in adolescent subjects and controls.

Results: The PCOS group had larger ovarian volume and higher measures of total testosterone and free androgen index than controls, but there were no differences in waist circumference, fasting glucose, blood pressure, or lipids. PCOS adolescents demonstrated more glucose abnormalities and higher plasminogen activator inhibitor-1. By pediatric criteria, 53% of the PCOS and 55% of the control adolescents had MBS. By adult criteria, 26% of PCOS and 29% of controls met diagnostic criteria for MBS.

Conclusions: Obese adolescent women have a high prevalence of MBS, and PCOS does not add additional risk for MBS. There appears to be an association between MBS and visceral adiposity. PCOS is associated with increased incidence of glucose intolerance and increased plasminogen activator inhibitor-1. Our results reinforce the importance of obesity counseling in adolescents to recognize the possible risk of future cardiovascular disease in these young women.
Le Soldat Sensible: Military Psychology and Social Egalitarianism in the Enlightenment French Army
Authors: Pichichero Christy
Published: September 2008

Between the end of the seventeenth century and that of the eighteenth, France's military decline sparked much thought regarding reforms that would increase combat effectiveness. While some reformers believed the problem to be technical and thus targeted tactical and organizational aspects of the military system, others maintained that the problem was moral, social, and political stemming from a corrupt civil society. Espousing a more anthropocentric and phenomenological account of war, the latter group pioneered ideas in military and social psychology that set the stage for changes in military policy and for the foundation of a more modern vision of selfhood and the experience of war.

Entre la fin du dix-septième siècle et celle du dix-huitième, le déclin militaire de la France suscita de nombreuses réflexions visant à améliorer les performances françaises sur le champ de bataille. Si certains objectèrent des défaillances techniques et proposèrent donc des ajustements tactiques et organisationnels du système militaire, d'autres soutinrent une origine morale, sociale et politique liée à l'état corrompu de la société civile. Epousant une analyse plus anthropocentrique et plus phénoménologique de la guerre, ce dernier groupe de penseurs développa de nouvelles idées portant sur la psychologie sociale et militaire et posant les jalons d'une conception plus moderne du « moi » et de l'expérience de la guerre.
No Right to Judge: Feminism and the Judiciary in Third Republic France
Authors: Kimble Sara L.
Published: September 2008

Women in France were admitted to the legal profession by law in 1900, but they were prohibited from ascending to the judiciary until 1946. Once they entered the profession, feminist lawyers demanded “the right to judge” and challenged gender discrimination in employment. They found allies among juvenile justice reformers who advocated the utility of placing women on the bench of the new youth courts created by the law of July 22, 1912. This article demonstrates that the legislative efforts to secure women's judicial eligibility were thwarted by the perception of women's social and cultural inferiority and by the fact of their legal inequality. Women's protest of their unequal treatment formed an inherent claim to equal citizenship and threatened to disrupt the traditional power relations between the sexes.

Les femmes françaises ont gagné le droit d'exercer le métier d'avocate en 1900, mais elles n'ont pas pu devenir juges avant 1946. Une fois entrées dans la profession, les avocates féministes ont réclamé « le droit de juger » et ont défié la discrimination contre les femmes au travail. Elles ont trouvé des alliés parmi les réformateurs du système judiciaire juvénile qui préconisaient de permettre aux femmes d'exercer le métier de juge dans les nouveaux tribunaux pour enfants et adolescents créés par la loi du 22 juillet 1912. Cet article démontre que les tentatives de réforme législative visant de permettre aux femmes de devenir juges ont été bloquées par la perception de l'inégalité sociale et culturelle de la femme, et par son incapacité politique. Les revendications professionnelles des avocates impliquaient le droit à la citoyenneté, et menaçaient de bouleverser le rapport traditionnel entre les sexes.
Radio Broadcasting, Disabled Veterans, and the Politics of National Recovery in Interwar France
Authors: Scales Rebecca
Published: September 2008

In interwar France a public consensus emerged that radio broadcasting could advance the rehabilitation of disabled veterans and further their reintegration into civil society. Radio appeared to offer particular advantages for blind and deaf veterans, serving as a “prosthesis” to replace their damaged eyes and ears. Thanks to two national charities that distributed free radios to the blind, the hospitalized, and the “infirm” between 1928 and 1935, facilitating disabled veterans' access to radio became a political imperative. The subsequent negotiations between physicians, legislators, and veterans themselves over the rehabilitative function of radio reveal how the airwaves became a virtual representation of the French nation and listening a practice of modern citizenship.

Dans la France d'entre-deux-guerres, le public se trouvait en accord général sur le fait que la radiodiffusion pouvait faire avancer la rééducation des invalides de guerre et leur réinsertion dans la société civile. La radiodiffusion s'offrait en particulier aux aveugles et « sourds » de guerre, remplaçant, en fonction de « prosthèse », les yeux et les oreilles mutilés. Entre 1928 et 1935, grâce à deux collectes nationales qui distribuaient des radios gratuites aux aveugles, hospitalisés, et « infirmes », le défi de faciliter l'accès des invalides de guerre à la radio s'est imposé sur la politique. Les négociations ultérieures entre médecins, législateurs, et invalides de guerre eux-mêmes à propos de la fonction rééducative de la radio montrent comment les ondes sont devenues une représentation virtuelle de la nation et l'écoute importante de la pratique de la citoyenneté moderne.
Colonialism in Equality: Hawaiian Sovereignty and the Question of U.S. Civil Rights
Authors: Kauanui J. Kēhaulani
Published: September 2008

This essay focuses on the case study of Native Hawaiians and the backlash against sovereignty struggles by neoconservatives who appropriate civil rights rhetoric to claim “reverse racism” in order to dismiss indigenous national claims as exclusionary. For indigenous peoples in the United States, along with those in the U.S. territories who may or may not be indigenous, the political project of civil rights throughout the last forty years has always been fraught, given the history of U.S. settler colonialism, distinctly different relationships to the nation-state, as well as different types of citizenship, and especially given the history of forced inclusion within the United States as the American Republic appropriated indigenous territory in the service of imperialist expansion. Thus, issues relating to territory, sovereignty, and nationhood structure colonized peoples' relationship to the nation-state and make for radically different goals than those that emerge from the project of civil rights. The conflation of race and indigeneity is one of the central problems in asserting the distinction between civil rights and sovereignty claims, especially as the racialization of native peoples as both “special interest groups” and “racial minorities” is deployed in the service of undermining the unique legal status of indigenous peoples under both U.S. federal law and international law. This changing political terrain creates the need for multiple interventions on different fronts when challenging the logic and workings of settler colonialism.
“We are all Israelis”: The Politics of Colonial Comparisons
Authors: Lubin Alex
Published: September 2008

Drawing on the work of Benedict Anderson and Edward Said, this essay analyzes the ubiquity of comparisons in American Orientalist culture. As the United States gained territory through settler colonial expansion, it often rendered its acquisition meaningful through comparisons to Levantine culture. Hence, in his 1848 account of the U.S. naval expedition of the Red Sea and Jordan, William Lynch compared Arabs to Indians and the Holy Land to the U.S. Southwest. During the Gilded Age, Mark Twain compared Palestinian villages to western U.S. mining camps. In the 1940s, World War II war correspondents compared the Moroccan Sahara to El Paso and New Mexican pueblos.

Yet, comparisons are also the rubric of critical colonial studies that unmask forms of exceptionalism and colonial rule. The comparative maneuvers that constitute American Orientalism unwittingly invite comparisons of colonial power. I therefore read critically against American Orientalism by focusing on a comparative analysis of the U.S.-Mexico and Israeli “security walls,” as well as Palestinian and Louisianan refugees. This enables one to reveal the haunting specter, to cite Anderson, of comparative work.
The American Construction of the Poor White Problem in South Africa
Authors: Magubane Zine
Published: September 2008

This essay examines the circuits of knowledge production that made comparisons between poor whites in the United States and South Africa pertinent and possible. It focuses on a five-volume study funded by the Carnegie Corporation of New York. The study, commissioned in the late 1920s and carried out in the early 1930s, covered all aspects of white rural poverty in South Africa. The first part of the essay discusses what made these comparisons possible by showing how American philanthropic organizations—especially the Carnegie Corporation—carved out spaces for the production and exchange of intellectuals, research paradigms, and theoretical models. The second part of the essay turns to a discussion of what made these comparisons pertinent. The defense of racial capitalism relied on gender and race discourses that put the responsibility for maintaining the prestige of the white race on white women. Reformers, social scientists, elected officials, and philanthropists believed that the so-called poor white problem was a result of the backwardness of the home, which they blamed on inept poor white mothers. Thus, the notion of poor whiteism also became deeply gendered.
The Perils of Separation: Fouzi El-Asmar's To Be an Arab in Israel as an Allegory of Settler Colonial Anxiety
Authors: Abraham Matthew
Published: September 2008

This essay uses Fouzi El-Asmar's To Be an Arab in Israel as a point of departure to examine the plight of Israel's Palestinian Arab citizens since 1948, while also exploring the inherent contradictions within the logic and political economy of Zionism that situate Palestinians as a persistent and disturbing reminder of Israel's settler colonial aspirations. By taking inventory of the various ontological crises attending what it means to be a Palestinian living in Israel, as well as the historical vectors informing Zionism's various attempts to prevent the development of Palestinian civil society, Abraham argues that there are clear analogues between Palestinian and Jewish suffering. After completing a theoretical survey of the arguments informing defenses of, and apologies for, Israel's occupation of the West Bank and destruction of Gaza, Abraham turns to the ways in which the Holocaust has been used to shore up connections between Zionist and Jewish history. Finally, the essay turns to recent intellectual and media controversies attending comparisons between Israeli and South African apartheid, focusing on the attacks on Jimmy Carter's Palestine: Peace Not Apartheid. In conclusion, Abraham argues that the Israel-Palestinian conflict cannot be solved until Israel's Palestinian Arab citizens are recognized as equals with their Jewish brethren.
Imperial Fantasies, Colonial Realities: Contesting Power and Culture in Italian Eritrea
Authors: Makki Fouad
Published: September 2008

There is today widespread recognition that colonialism was ultimately about the institutionalization of an imaginary of profound social inequality anchored in relations of production and asymmetries of power that were justified by ideologies of racial superiority. The assertion of the final alterity of the colonized was crucial to this imaginary and entailed the construction of a social and political order founded on a multidimensional polarity. But the taxonomies of difference that structured these polarities were never as fixed or impermeable as the colonizers imagined them to be. It was in actuality precisely along the indeterminate boundaries between those categories of rule—at the crossroads of politics and culture—that everyday challenges to colonial hegemony were vitally posed, casting doubt on its founding myths and forms of power. My intention in this essay is to explore this cultural politics of colonialism in the context of Italian Eritrea. The emphasis will be on the period after the demise of a settler colonial project, which came to an abrupt end in the face of peasant resistance and Italian military defeat at the Battle of Adwa in 1896. The rupture of the settler project and the forced political retreat made it particularly difficult to sustain the distinctions on which colonial power rested. The subsequent fashioning of a new colonial project was indelibly marked by the experience of defeat that haunted the Italian colonial imagination, which makes Eritrea a particularly propitious context for examining the “tensions of empire.”