bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytomegalovirus Infection- and Age-Dependent Changes in Human CD8
+
T-Cell Cytokine Expression Patterns
Authors: Faist Benjamin , Fleischer Bernhard , Jacobsen Marc 
Published: April 2010

ABSTRACT

T cells are strongly affected by immune aging, a phenomenon that leads to increased susceptibility to infections and decreased vaccination efficacy in elderly individuals. Cytomegalovirus (CMV) infection induces vigorous T-cell immune responses in humans and is thought to be a driving force of immune aging. In the present study we analyzed CMV-induced quantitative and qualitative differences in the cytokine-expressing T-cell repertoire from individuals of different age groups after
in vitro
stimulation. The CMV pp65 peptide pool and the superantigen
Staphylococcus
enterotoxin B (SEB) induced higher proportions of CD8
+
effector T cells expressing gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor in the oldest study group, while only SEB induced increased responses in the middle-aged study group. Notably, CMV-specific multiple cytokine expression patterns revealed higher proportions of IFN-γ- and TNF-α-coexpressing CD8
+
T cells exclusively in the oldest study group. These qualitative differences were absent in SEB-induced CD8
+
effector T cells, although quantitative differences were detected. We report age-dependent qualitative changes in CMV-specific CD8
+
T-cell cytokine patterns which are biocandidate markers of immune exhaustion in elderly individuals.
Core Antigen Expression Is Associated with Hepatic Necroinflammation in e Antigen-Negative Chronic Hepatitis B Patients with Low DNA Loads
Authors: Huang Yi-Hsiang , Hung Hung-Hsu , Chan Che-Chang , Lai Chiung-Ru , Chu Chi-Jen , Huo Teh-Ia , Lee Pui-Ching , Su Chien-Wei , Lan Keng-Hsin , Huang Hui-Chun , Lee I-Cheng , Lin Han-Chieh , Lee Shou-Dong 
Published: April 2010

ABSTRACTIntrahepatic hepatitis B virus (HBV) core antigen (HBcAg) is a hallmark of viral replication in hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B (CHB). The aim of this study was to evaluate the role of HBcAg in HBeAg-negative CHB. One hundred six HBeAg-negative CHB patients who underwent ultrasonographically guided liver biopsy were reviewed for their HBV DNA load and clinical and histological data. Factors associated with the expression of intrahepatic HBcAg were analyzed. Among the patients, 35 (33%) were positive for HBcAg by immunohistostaining. In patients whose HBV DNA loads were higher than 107copies (cp)/ml, nearly one-half (52%) had detectable HBcAg. Compared with HBcAg-negative patients, HBcAg-positive patients had higher serum alanine transaminase (ALT) and HBV DNA levels and more-severe hepatic necroinflammation. High serum ALT level (>160 U/liter) and HBV viral load were the determinants of HBcAg expression in multivariate analysis. Large amounts of HBcAg expression were frequently detected in patients with high DNA loads, and the patterns of HBcAg distribution were not related to histological activity or HBV DNA levels. In patients with lower HBV DNA loads, the expression of HBcAg was the key factor associated with active hepatic necroinflammation (hazard ratio = 11.25; 95% confidence interval [CI], 1.42 to 89.26;P= 0.022). In conclusion, the expression of HBcAg is not frequent in HBeAg-negative CHB. The expression of intrahepatic HBcAg indicates active hepatic necroinflammation, even in patients with low HBV DNA load. Both HBV viral load and HBcAg expression have implications in the pathogenesis of HBeAg-negative CHB.
Multicenter Collaborative Study for Standardization ofCandida albicansGenotyping Using a Polymorphic Microsatellite Marker
Authors: Garcia-Hermoso Dea , MacCallum Donna M. , Lott Timothy J. , Sampaio Paula , Serna Maria-José Buitrago , Grenouillet Fréderic , Klaassen Corné H. W. , Bretagne Stéphane 
Published: April 2010

ABSTRACTMicrosatellite-based genotyping forCandida albicanscan give discrepant results between laboratories when expressed in fragment sizes, because their determination depends on electrophoretic conditions. The interlaboratory reproducibility was assessed in six laboratories provided with an allelic ladder. Despite variations in size determinations, alleles were correctly assigned, making data transportable between laboratories.
Evolution of Endogenous Sequences of
Banana Streak Virus
: What Can We Learn from Banana (
Musa
sp.) Evolution?
Authors: Gayral Philippe , Blondin Laurence , Guidolin Olivier , Carreel Françoise , Hippolyte Isabelle , Perrier Xavier , Iskra-Caruana Marie-Line 
Published: April 2010

ABSTRACT

Endogenous plant pararetroviruses (EPRVs) are viral sequences of the family
Caulimoviridae
integrated into the nuclear genome of numerous plant species. The ability of some endogenous sequences of
Banana streak viruses
(eBSVs) in the genome of banana (
Musa
sp.) to induce infections just like the virus itself was recently demonstrated (P. Gayral et al., J. Virol. 83:6697-6710, 2008). Although eBSVs probably arose from accidental events, infectious eBSVs constitute an extreme case of parasitism, as well as a newly described strategy for vertical virus transmission in plants. We investigated the early evolutionary stages of infectious eBSV for two distinct BSV species—GF (BSGFV) and Imové (BSImV)—through the study of their distribution, insertion polymorphism, and structure evolution among selected banana genotypes representative of the diversity of 60 wild
Musa
species and genotypes. To do so, the historical frame of host evolution was analyzed by inferring banana phylogeny from two chloroplast regions—
matK
and
trnL-trnF
—as well as from the nuclear genome, using 19 microsatellite loci. We demonstrated that both BSV species integrated recently in banana evolution, circa 640,000 years ago. The two infectious eBSVs were subjected to different selective pressures and showed distinct levels of rearrangement within their final structure. In addition, the molecular phylogenies of integrated and nonintegrated BSVs enabled us to establish the phylogenetic origins of eBSGFV and eBSImV.
New Strategies in Head and Neck Cancer: Understanding Resistance to Epidermal Growth Factor Receptor Inhibitors
Authors: Chen Lucy F. , Cohen Ezra E.W. , Grandis Jennifer R. 
Published: April 2010

AbstractThe epidermal growth factor receptor (EGFR) is a validated target in squamous cell carcinoma of the head and neck (HNSCC). However, despite high expression of EGFR in these cancers, EGFR inhibitor monotherapy has only had modest activity. Potential mechanisms of resistance to EGFR-targeted therapies involve EGFR and Ras mutations, epithelial-mesenchymal transition, and activation of alternative and downstream pathways. Strategies to optimize EGFR-targeted therapy in head and neck cancer involve not only the selection for patients most likely to benefit but also the use of combination therapies to target the network of pathways involved in tumor growth, invasion, angiogenesis, and metastasis. Clin Cancer Res; 16(9); 2489–95. ©2010 AACR.
Spectrum of causative mutations in patients with haemophilia A in Austria
Authors: Reitter Sylvia , Sturn Rümuth , Horvath Birgit , Freitag Renate , Male Christoph , Muntean Wolfgang , Streif Werner , Pabinger Ingrid , Mannhalter Christine ,   and the Austrian Molecular Haemophilia Study Group
Published: April 2010

SummaryIn patients with haemophilia A knowledge of the pathogenetic mutation is important i) as basis for carrier diagnosis and ii) for risk estimation of inhibitor formation. The pathogenetic mutations were identified by testing inversions in intron 1 and 22 (IVS22 and IVS1) and sequencing part of the promoter, the coding region and the exon/intron boundaries in a cohort of Austrian haemophilia A patients. A total of 239 patients from nine participating centres, who had consented to genetic testing and of whom clinical information was available were included in the study. First, IVS22 and IVS1 were tested; in case of absence of either inversion patients were subjected to sequencing. Mutations within the FVIII gene were identified in 234 patients. Notably, 53 mutations had not previously been described in HAMSTeRS. Of our patient cohort, 72.5 % had either an IVS22 or a missense mutation. Interestingly, in three brothers with severe haemophilia, we found a double mutation in exon 14 (missense + small deletion). The spectrum of mutations in Austrian haemophilia A patients was comparable to that found in the German and Italian population; however, it differed from the spectrum reported in the UK. In conclusion, 53 not previously published mutations were identified in Austrian haemophilia A patients. The occurrence of double mutations in the factor VIII gene could be confirmed and their low frequency was corroborated. We speculate that the differences between mutations in Austria and other European countries are due to ethnic diversity. Detailed investigations of the association of ethnicity and the mutation spectrum are planned.
Changing Roles of International Organizations: Global Administrative Law and the Interplay of Legitimacies
Authors: de Chazournes Laurence Boisson 
Published: April 2010

AbstractLooking back over the last sixty years, there is no doubt that the role and the capacity of international organizations to conduct operations have greatly evolved. Their mandates have expanded and the objectives to be reached have been diversified. Field operations have increased in a dramatic way. It has become increasingly necessary for international organizations to resort to innovative legal mechanisms to be able to fulfil the new tasks they have been assigned. In the meantime, the appearance on the world stage of a large number of non-State actors carrying out tasks which were traditionally incumbent upon State authorities and intergovernmental organisations, has led to the establishment of specific mechanisms allowing them to collaborate closely with the latter. In face of the challenges raised by these complex interlocking legal relationships, numerous administrative law type principles have emerged as instruments for adapting the classic international system of States and intergovernmental organizations to contemporary requirements.
BiGG: a Biochemical Genetic and Genomic knowledgebase of large scale metabolic reconstructions
Authors: Schellenberger Jan , Park Junyoung O , Conrad Tom M , Palsson Bernhard Ø 
Published: April 2010

Abstract

Background
Genome-scale metabolic reconstructions under the Constraint Based Reconstruction and Analysis (COBRA) framework are valuable tools for analyzing the metabolic capabilities of organisms and interpreting experimental data. As the number of such reconstructions and analysis methods increases, there is a greater need for data uniformity and ease of distribution and use.

Description
We describe BiGG, a knowledgebase of Biochemically, Genetically and Genomically structured genome-scale metabolic network reconstructions. BiGG integrates several published genome-scale metabolic networks into one resource with standard nomenclature which allows components to be compared across different organisms. BiGG can be used to browse model content, visualize metabolic pathway maps, and export SBML files of the models for further analysis by external software packages. Users may follow links from BiGG to several external databases to obtain additional information on genes, proteins, reactions, metabolites and citations of interest.

Conclusions
BiGG addresses a need in the systems biology community to have access to high quality curated metabolic models and reconstructions. It is freely available for academic use at http://bigg.ucsd.edu.
Bacillus anthracis genome organization in light of whole transcriptome sequencing
Authors: Martin Jeffrey , Zhu Wenhan , Passalacqua Karla D , Bergman Nicholas , Borodovsky Mark 
Published: April 2010

Abstract
Emerging knowledge of whole prokaryotic transcriptomes could validate a number of theoretical concepts introduced in the early days of genomics. What are the rules connecting gene expression levels with sequence determinants such as quantitative scores of promoters and terminators? Are translation efficiency measures, e.g. codon adaptation index and RBS score related to gene expression? We used the whole transcriptome shotgun sequencing of a bacterial pathogen Bacillus anthracis to assess correlation of gene expression level with promoter, terminator and RBS scores, codon adaptation index, as well as with a new measure of gene translational efficiency, average translation speed. We compared computational predictions of operon topologies with the transcript borders inferred from RNA-Seq reads. Transcriptome mapping may also improve existing gene annotation. Upon assessment of accuracy of current annotation of protein-coding genes in the B. anthracis genome we have shown that the transcriptome data indicate existence of more than a hundred genes missing in the annotation though predicted by an ab initio gene finder. Interestingly, we observed that many pseudogenes possess not only a sequence with detectable coding potential but also promoters that maintain transcriptional activity.
Quantitative polymerase chain reaction analysis by deconvolution of internal standard
Authors: Hirakawa Yasuko , Medh Rheem D , Metzenberg Stan 
Published: April 2010

Abstract

Background
Quantitative Polymerase Chain Reaction (qPCR) is a collection of methods for estimating the number of copies of a specific DNA template in a sample, but one that is not universally accepted because it can lead to highly inaccurate (albeit precise) results. The fundamental problem is that qPCR methods use mathematical models that explicitly or implicitly apply an estimate of amplification efficiency, the error of which is compounded in the analysis to unacceptable levels.

Results
We present a new method of qPCR analysis that is efficiency-independent and yields accurate and precise results in controlled experiments. The method depends on a computer-assisted deconvolution that finds the point of concordant amplification behavior between the "unknown" template and an admixed amplicon standard. We apply the method to demonstrate dexamethasone-induced changes in gene expression in lymphoblastic leukemia cell lines.

Conclusions
This method of qPCR analysis does not use any explicit or implicit measure of efficiency, and may therefore be immune to problems inherent in other qPCR approaches. It yields an estimate of absolute initial copy number of template, and controlled tests show it generates accurate results.
High-efficiency transfection of cultured primary motor neurons to study protein localization, trafficking, and function
Authors: Fallini Claudia , Bassell Gary J , Rossoll Wilfried 
Published: April 2010

Abstract

Background
Cultured spinal motor neurons are a valuable tool to study basic mechanisms of development, axon growth and pathfinding, and, importantly, to analyze the pathomechanisms underlying motor neuron diseases. However, the application of this cell culture model is limited by the lack of efficient gene transfer techniques which are available for other neurons. To address this problem, we have established magnetofection as a novel method for the simple and efficient transfection of mouse embryonic motor neurons. This technique allows for the study of the effects of gene expression and silencing on the development and survival of motor neurons.

Results
We found that magnetofection, a novel transfection technology based on the delivery of DNA-coated magnetic nanobeads, can be used to transfect primary motor neurons. Therefore, in order to use this method as a new tool for studying the localization and transport of axonal proteins, we optimized conditions and determined parameters for efficient transfection rates of >45% while minimizing toxic effects on survival and morphology. To demonstrate the potential of this method, we have used transfection with plasmids encoding fluorescent fusion-proteins to show for the first time that the spinal muscular atrophy-disease protein Smn is actively transported along axons of live primary motor neurons, supporting an axon-specific role for Smn that is different from its canonical function in mRNA splicing. We were also able to show the suitability of magnetofection for gene knockdown with shRNA-based constructs by significantly reducing Smn levels in both cell bodies and axons, opening new opportunities for the study of the function of axonal proteins in motor neurons.

Conclusions
In this study we have established an optimized magnetofection protocol as a novel transfection method for primary motor neurons that is simple, efficient and non-toxic. We anticipate that this novel approach will have a broad applicability in the study of motor neuron development, axonal trafficking, and molecular mechanisms of motor neuron diseases.
Dynamics and Control of the Central Carbon Metabolism in Hepatoma Cells
Authors: Maier Klaus , Hofmann Ute , Reuss Matthias , Mauch Klaus 
Published: April 2010

Abstract

Background
The liver plays a major role in metabolism and performs a number of vital functions in the body. Therefore, the determination of hepatic metabolite dynamics and the analysis of the control of the respective biochemical pathways are of great pharmacological and medical importance. Extra- and intracellular time-series data from stimulus-response experiments are gaining in importance in the identification of in vivo metabolite dynamics, while dynamic network models are excellent tools for analyzing complex metabolic control patterns. This is the first study that has been undertaken on the data-driven identification of a dynamic liver central carbon metabolism model and its application in the analysis of the distribution of metabolic control in hepatoma cells.

Results
Dynamic metabolite data were collected from HepG2 cells after they had been deprived of extracellular glucose. The concentration of 25 extra- and intracellular intermediates was quantified using HPLC, LC-MS-MS, and GC-MS. The in silico metabolite dynamics were in accordance with the experimental data. The central carbon metabolism of hepatomas was further analyzed with a particular focus on the control of metabolite concentrations and metabolic fluxes. It was observed that the enzyme glucose-6-phosphate dehydrogenase exerted substantial negative control over the glycolytic flux, whereas oxidative phosphorylation had a significant positive control. The control over the rate of NADPH consumption was found to be shared between the NADPH-demand itself (0.65) and the NADPH supply (0.38).

Conclusions
Based on time-series data, a dynamic central carbon metabolism model was developed for the investigation of new and complex metabolic control patterns in hepatoma cells. The control patterns found support the hypotheses that the glucose-6-phosphate dehydrogenase and the Warburg effect are promising targets for tumor treatment. The systems-oriented identification of metabolite dynamics is a first step towards the genome-based assessment of potential risks posed by nutrients and drugs.
Concomitant homozygosity for the prothrombin gene variant with mild deficiency of antithrombin III in a patient with multiple hepatic infarctions: a case report
Authors: Emmanuelle Theodore , Husein Belkys , Iqbal Javaid , Macheta M , Isaacs Peter 
Published: April 2010

Abstract

Introduction
Hereditary causes of visceral thrombosis or thrombosis should be sought among young patients. We present a case of a young man presenting with multiple hepatic infarctions resulting in portal hypertension due to homozygosity of the prothrombin gene mutation not previously described in literature.

Case presentation
A 42-year-old Caucasian man with a previous history of idiopathic deep vein thrombosis 11 years earlier presented with vague abdominal pains and mildly abnormal liver function tests. An ultrasound and computed tomography scan showed evidence of hepatic infarction and portal hypertension (splenic varices). A thrombophilia screen confirmed a homozygous mutation for the prothrombin gene mutation, with mildly reduced levels of anti-thrombin III (AT III). Subsequent testing of his father and brother revealed heterozygosity for the same gene mutation.

Conclusion
Hepatic infarction is unusual due to the rich dual arterial and venous blood supply to the liver. In the absence of an arterial or haemodynamic insult causing hepatic infarction, a thrombophilia should be considered. To our knowledge, this is the first reported case of a hepatic infarction due to homozygosity of the prothrombin gene mutation. It is unclear whether homozygotes have a higher risk of thrombosis than heterozygotes. In someone presenting with a first thrombosis with this mutation, the case for life-long anticoagulation is unclear, but it may be necessary to prevent a second and more severe second thrombotic event, as occurred in this case.
Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor
Authors: Balsa Alejandro , Cabezón Arancha , Orozco Gisela , Cobo Tatiana , Miranda-Carus Eugenia , López-Nevot Miguel Ángel , Vicario José Luis , Martín-Mola Emilio , Martín Javier , Pascual-Salcedo Dora 
Published: April 2010

Abstract
Introduction
The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).

Methods
We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.

Results
We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.

Conclusions
HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.