bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

AbstractCompromised 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.001) and decreased SHBG (P = 0.02) in women and, in men, increased DHEAS, E1, FEI (all P &lt; 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 &lt; 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.