Search

Peripheral blood mononuclear cells (PBMCs) are blood cells that are a critical part of the immune system used to fight off infection, defending our bodies from harmful pathogens. In biomedical research, PBMCs are commonly used to study global immune response to disease outbreak and progression, pathogen infections, for vaccine development and a multitude of other clinical applications. Over the past few years, the revolution in single-cell RNA sequencing (scRNA-seq) has enabled an unbiased quantification of gene expression in thousands of individual cells, which provides a more efficient tool to decipher the immune system in human diseases. In this work, we generate scRNA-seq data from human PBMCs at high sequencing depth (>100,000 reads/cell) for more than 30,000 cells, in resting, stimulated, fresh and frozen conditions. The data generated can be used for benchmarking batch correction and data integration methods, and to study the effect of freezing-thawing cycles on the quality of immune cell populations and their transcriptomic profiles. [ABSTRACT FROM AUTHOR]

Purpose: Staphylococcus aureus (SA) is involved in almost one-third of endocarditis events (known as E-SA) and is frequently associated with unfavorable outcomes compared to infectious endocarditis (IE) caused by other pathogens including coagulase-negative staphylococci (CNS). The aim of this study was to compare the morbidity and mortality of patients with E-SA and endocarditis due to CNS (known as E-CNS). Methods: A monocentric retrospective cohort analysis was conducted including all patients admitted with IE from January 2010 to December 2017. Lengths of stay, complications, in-hospital and 1-year mortality were described from medical records and compared between E-SA and E-CNS. Results: Among the 428 patients included, 102 had staphylococcus (50 E-SA and 52 E-CNS). Half of the IE events due to staphylococcus occurred in the year following a cardiac procedure [p = 0.029]. A septic embolism occurred in 41% and 48% of patients with E-CNS and E-SA, respectively [p = 0.439]. Cardiac surgery was indicated in 50% of E-SA and 48% of E-CNS cases [p = 0.846]. The intra-hospital and 1-year mortality rates were 25% and 31% for E-CNS and 34% and 45% for E-SA [p = 0.699, p = 0.234]. Conclusion: Embolic complications, surgical management rate and mortality rates of E-SA and E-CNS were comparable, which may suggest a similar morbidity and mortality irrespective of the pathogen involved in IE. [ABSTRACT FROM AUTHOR]

The equation of state with light clusters for nuclear and stellar matter is determined using chemical equilibrium constants evaluated from the analysis of the recently published (Xe + Sn) heavy ion data, corresponding to three reactions with different isotopic contents of the emission source. The measured multiplicities are used to extract the thermodynamic properties, and an in-medium correction to the ideal gas internal partition function of the clusters is included in the analysis. This in-medium correction and its respective uncertainty are calculated via a Bayesian analysis, with the unique hypothesis that the different nuclear species in a given sample must correspond to a unique common value for the density of the expanding source. Different parameter sets for the correction are tested, and the effect of the radius of the clusters on the thermodynamics and on the chemical equilibrium constants is also addressed. It is shown that the equilibrium constants obtained are almost independent of the isospin content of the analysed systems. Finally, a comparison with a relativistic mean field model proves that data are consistent with a universal in-medium correction of the scalar σ-meson coupling for nucleons bound in clusters. The obtained value, , is larger than that obtained in a previous study not including in-medium effects in the data analysis. This result implies a smaller effect on the binding energy of the clusters and, as a consequence, larger melting densities, and an increased cluster contribution in supernova matter. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a progressive, inflammatory autoimmune disease of unknown aetiology. The complex mechanism of aetiopathogenesis, progress and chronicity of the disease involves genetic, epigenetic and environmental factors. To understand the molecular mechanisms underlying disease phenotypes, one has to place implicated factors in their functional context. However, integration and organization of such data in a systematic manner remains a challenging task. Molecular maps are widely used in biology to provide a useful and intuitive way of depicting a variety of biological processes and disease mechanisms. Recent large-scale collaborative efforts such as the Disease Maps Project demonstrate the utility of such maps as versatile tools to organize and formalize disease-specific knowledge in a comprehensive way, both human and machine-readable. We present a systematic effort to construct a fully annotated, expert validated, state-of-the-art knowledge base for RA in the form of a molecular map. The RA map illustrates molecular and signalling pathways implicated in the disease. Signal transduction is depicted from receptors to the nucleus using the Systems Biology Graphical Notation (SBGN) standard representation. High-quality manual curation, use of only human-specific studies and focus on small-scale experiments aim to limit false positives in the map. The state-of-the-art molecular map for RA, using information from 353 peer-reviewed scientific publications, comprises 506 species, 446 reactions and 8 phenotypes. The species in the map are classified to 303 proteins, 61 complexes, 106 genes, 106 RNA entities, 2 ions and 7 simple molecules. The RA map is available online at ramap.elixir-luxembourg.org as an open-access knowledge base allowing for easy navigation and search of molecular pathways implicated in the disease. Furthermore, the RA map can serve as a template for omics data visualization. [ABSTRACT FROM AUTHOR]

Labelled leucocyte scintigraphy (LS) is regarded as helpful when exploring bone and joint infections. The aim of this study was to evaluate the utility of LS for the diagnosis of chronic periprosthetic joint infections (PJIs) in patients exhibiting arthroplastic loosening. One hundred sixty-eight patients were referred to centres for treatment of complex PJI. One hundred fifty underwent LS using 99mTc-HMPAO (LLS); 18 also underwent anti-granulocyte scintigraphy (AGS) and 13 additional SPECT with tomodensitometry imaging (SPECT-CT). The LS results were compared with bone scan data. For all, the final diagnoses were determined microbiologically; perioperative samples were cultured. LS values were examined, as well as sensitivity by microorganism, anatomical sites, and injected activity. LS results were also evaluated according to the current use of antibiotics or not. The sensitivity, specificity, and positive predictive value of LLS were 72%, 60%, and 80%, respectively. LLS performed better than did AGS. SPECT-CT revealed the accurate locations of infections. The sensitivity of LS was not significantly affected by the causative pathogen or the injected activity. No correlation was evident between the current antibiotic treatment and the LS value. The test was more sensitive for knee (84%) than hip arthroplasty (57%) but was less specific for knee (52% vs. 75%). Sensitivity and specificity of LLS varied by the location of infection bone scan provide no additional value in PJI diagnosis. Current antibiotic treatment seems to have no influence on LS sensitivity as well as labelling leukocyte activity or pathogens responsible for chronic PJI. [ABSTRACT FROM AUTHOR]

Mathematical models can serve as a tool to formalize biological knowledge from diverse sources, to investigate biological questions in a formal way, to test experimental hypotheses, to predict the effect of perturbations and to identify underlying mechanisms. We present a pipeline of computational tools that performs a series of analyses to explore a logical model's properties. A logical model of initiation of the metastatic process in cancer is used as a transversal example. We start by analysing the structure of the interaction network constructed from the literature or existing databases. Next, we show how to translate this network into a mathematical object, specifically a logical model, and how robustness analyses can be applied to it. We explore the visualization of the stable states, defined as specific attractors of the model, and match them to cellular fates or biological read-outs. With the different tools we present here, we explain how to assign to each solution of the model a probability and how to identify genetic interactions using mutant phenotype probabilities. Finally, we connect the model to relevant experimental data: we present how some data analyses can direct the construction of the network, and how the solutions of a mathematical model can also be compared with experimental data, with a particular focus on high-throughput data in cancer biology. A step-by-step tutorial is provided as a Supplementary Material and all models, tools and scripts are provided on an accompanying website: https://github.com/sysbio-curie/Logical_modelling_pipeline. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) studies are becoming routinely used for the detection of novel and clinically actionable DNA variants at a pangenomic scale. Such analyses are now used in the clinical practice to enable precision medicine. Formalin-fixed paraffin-embedded (FFPE) tissues are still one of the most abundant source of cancer clinical specimen, unfortunately this method of preparation is known to degrade DNA and therefore compromise subsequent analysis. Some studies have reported that variant detection can be performed on FFPE samples sequenced with NGS techniques, but few or none have done an in-depth coverage analysis and compared the influence of different state-of-the-art FFPE DNA extraction kits on the quality of the variant calling. Here, we generated 42 human whole-exome sequencing data sets from fresh-frozen (FF) and FFPE samples. These samples include normal and tumor tissues from two different organs (liver and colon), that we extracted with three different FFPE extraction kits (QIAamp DNA FFPE Tissue kit and GeneRead DNA FFPE kit from Qiagen, Maxwell™ RSC DNA FFPE Kit from Promega). We determined the rate of concordance of called variants between matched FF and FFPE samples on all common variants (representing at least 86% of the total number of variants for SNVs). The concordance rate is very high between all matched FF / FFPE pairs, with equivalent values for the three kits we analyzed. On the other hand, when looking at the difference between the total number of variants in FF and FFPE, we find a significant variation for the three different FFPE DNA extraction kits. Coverage analysis shows that FFPE samples have less good indicators than FF samples, yet the coverage quality remains above accepted thresholds. We detect limited but statistically significant variations in coverage indicator values between the three FFPE extraction kits. Globally, the GeneRead and QIAamp kits have better variant calling and coverage indicators than the Maxwell kit on the samples used in this study, although this kit performs better on some indicators and has advantages in terms of practical usage. Taken together, our results confirm the potential of FFPE samples analysis for clinical genomic studies, but also indicate that the choice of a FFPE DNA extraction kit should be done with careful testing and analysis beforehand in order to maximize the accuracy of the results. [ABSTRACT FROM AUTHOR]

Purpose: Cases of fracture-fixation device infection involving Staphylococcus lugdunensis are not frequent. The clinical characteristics and the choice of treatment strategies of these infections are not obviously known to date.Methods: We performed a review of fracture-fixation device infection involving S. lugdunensis managed by our centres.Results: Among the 38 cases of fracture-fixation device infection involving S. lugdunensis, 53% were located in the tibia. Most of our cases (87%) were chronic infections. Purulent discharge, which occurred in 79% of cases, was the most frequent clinical symptom, followed by pain in 63%, local inflammation in 55%, and fever in 37%. Bacteremia and severe sepsis occurred in 10% and 18% of cases, respectively. Four cases (10%) were treated exclusively with antimicrobial treatment alone. Thirty-four cases (89%) were treated with a combination of surgery with antimicrobial therapy including surgical debridement, antibiotics and osteosynthesis device retention in six cases (16%), and osteosynthesis device removal in 27 cases (71%). The mean length of antibiotic treatment was 119 days. The relapse rate was high that was not related to selection of resistant strains. Polymicrobial infection had no impact on clinical outcome. A combination of surgery with antimicrobial therapy was identified as a significant prognostic factor associated with remission (p = 0.042).Conclusions: S. lugdunensis is probably involved in more infections than has been reported. Using appropriate microbiological methods laboratories should routinely identify the species of all coagulase-negative Staphylococci isolates involved in fracture-fixation device infection to better achieve the treatment strategies of fracture-fixation device infection involving S. lugdunensis. [ABSTRACT FROM AUTHOR]

Copyright of Cuadernos del Centro de Estudios de Diseño y Comunicación is the property of Cuadernos del Centro de Estudios de Diseno y Comunicacion and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In many analyses of high-throughput data in systems biology, there is a need to quantify the activity of a set of genes in individual samples. A typical example is the case where it is necessary to estimate the activity of a transcription factor (which is often not directly measurable) from the expression of its target genes. We present here ROMA (Representation and quantification Of Module Activities) Java software, designed for fast and robust computation of the activity of gene sets (or modules) with coordinated expression. ROMA activity quantification is based on the simplest uni-factor linear model of gene regulation that approximates the expression data of a gene set by its first principal component. The proposed algorithm implements novel functionalities: it provides several method modifications for principal components computation, including weighted, robust and centered methods; it distinguishes overdispersed modules (based on the variance explained by the first principal component) and coordinated modules (based on the significance of the spectral gap); finally, it computes statistical significance of the estimated module overdispersion or coordination. ROMA can be applied in many contexts, from estimating differential activities of transcriptional factors to finding overdispersed pathways in single-cell transcriptomics data. We describe here the principles of ROMA providing several practical examples of its use. ROMA source code is available at https://github.com/sysbio-curie/Roma. [ABSTRACT FROM AUTHOR]

The use of pneumococcal conjugate vaccine (PCV) in childhood pneumococcal immunization programs successfully reduced the incidence of pneumococcal disease in children. Nonetheless, there remains a high burden of pneumococcal disease in adults, especially the elderly, and children/adults with chronic medical conditions. Two pneumococcal vaccines are currently available for adults at risk of pneumococcal disease: the 23-valent pneumococcal polysaccharide vaccine (PPV23) and the more recently licensed PCV13. As it is not possible to determine vaccine efficacy in all populations at risk of pneumococcal disease, immunogenicity studies, measuring pneumococcal-specific antibody concentrations and/or the opsonophagocytic activity of serum can provide valuable comparative data for PPV and PCV immunization. This article provides consolidated data on the immunogenicity of PCVs (largely PCV7, and a few studies with PCV9 or PCV13) based on a review of immunogenicity/safety studies in populations (mainly pediatric) at increased risk of pneumococcal disease. [ABSTRACT FROM AUTHOR]

Module network inference is an established statistical method to reconstruct co-expression modules and their upstream regulatory programs from integrated multi-omics datasets measuring the activity levels of various cellular components across different individuals, experimental conditions or time points of a dynamic process. We have developed Lemon-Tree, an open-source, platform-independent, modular, extensible software package implementing state-of-the-art ensemble methods for module network inference. We benchmarked Lemon-Tree using large-scale tumor datasets and showed that Lemon-Tree algorithms compare favorably with state-of-the-art module network inference software. We also analyzed a large dataset of somatic copy-number alterations and gene expression levels measured in glioblastoma samples from The Cancer Genome Atlas and found that Lemon-Tree correctly identifies known glioblastoma oncogenes and tumor suppressors as master regulators in the inferred module network. Novel candidate driver genes predicted by Lemon-Tree were validated using tumor pathway and survival analyses. Lemon-Tree is available from under the GNU General Public License version 2.0. [ABSTRACT FROM AUTHOR]

Background: HIV-infected patients starting antiretroviral treatment (ART) experience deep and early disorders in fat and bone metabolism, leading to concomitant changes in fat mass and bone mineral density. Methods: We conducted a prospective study in treatment-naive HIV-infected patients randomized to receive two nucleoside reverse transcriptase inhibitors in combination with either a protease inhibitor (PI) or a non-nucleosidic reverse transcriptase inhibitor (NNRTI), to evaluate early changes in body composition, bone mineral density and metabolic markers as differentially induced by antiretroviral therapies. We measured changes in markers of carbohydrate, of fat and bone metabolism, and, using dual-emission X-ray absorptiometry (DXA), body composition and bone mineral density (BMD). Complete data on changes between baseline and after 21 months treatment were available for 35 patients (16 in the PI group and 19 in the NNRTI group). Results: A significant gain in BMI and in total and lower limb fat mass was recorded only in patients receiving PI. A loss of lumbar BMD was observed in both groups, being higher with PI. Plasma markers of bone metabolism (alkaline phosphatase, osteocalcin, collagen crosslaps) and levels of parathormone and of 1,25diOH-vitamin D3 significantly increased in both groups, concomitant with a decline in 25OH-vitamin D3. Lipids and glucose levels increased in both groups but rise in triglyceride was more pronounced with PI. A correlation between loss of BMD and gain of fat mass is observed in patients starting PI. Conclusions: We evidenced an early effect of ART on lipid and bone metabolisms. PI lead to a significant gain in fat mass correlated with a sharp drop in BMD but active bone remodelling is evident with all antiretroviral treatments, associated with low vitamin D levels and hyperparathyroidism. In parallel, signs of metabolic restoration are evident. However, early increases in lean and fat mass, triglycerides, waist circumference and leptin are much more pronounced with PI. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae is the leading cause of bacterial meningitis. Young children, the elderly and those who are immunocompromised or who suffer from chronic diseases have the highest risk of developing pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the US and in 2001 in Europe.Methods: A literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal diseases. Here, we report the impact on pneumococcal meningitis.Results: A total of 17 articles reporting impact data on pneumococcal meningitis were included in this review: 11 from Western Europe and 6 from North America. In the post-vaccination period, compared with the pre-vaccination period, a reduction ranging from 59.2% in the US, 1 year after vaccine introduction, to 100% in Belgium, 4 years after vaccine introduction in vaccine-type (VT) pneumococcal meningitis incidence was reported in vaccine-eligible children in seven studies. In addition, the majority of studies reported reductions in VT and all-type pneumococcal meningitis incidence in age groups that were not vaccine-eligible.Conclusions: The results from this review demonstrate that PCV7 has had a significant impact on pneumococcal meningitis across all ages through its use in pediatric immunization programs. With the introduction of 13-valent PCV (PCV13) we can expect to see a reduction in the incidence of pneumococcal meningitis due to the six additional serotypes included, as well as continued protection against pneumococcal meningitis due to PCV7 serotypes. Robust surveillance systems are essential for the evaluation of the impact of PCV13 on all-type pneumococcal meningitis and for monitoring the evolution of non-vaccine serotype pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae is the leading cause of bacterial meningitis. Young children, the elderly and those who are immunocompromised or who suffer from chronic diseases have the highest risk of developing pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the US and in 2001 in Europe. Methods: A literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal diseases. Here, we report the impact on pneumococcal meningitis. Results: A total of 17 articles reporting impact data on pneumococcal meningitis were included in this review: 11 from Western Europe and 6 from North America. In the post-vaccination period, compared with the pre-vaccination period, a reduction ranging from 59.2% in the US, 1 year after vaccine introduction, to 100% in Belgium, 4 years after vaccine introduction in vaccine-type (VT) pneumococcal meningitis incidence was reported in vaccine-eligible children in seven studies. In addition, the majority of studies reported reductions in VT and all-type pneumococcal meningitis incidence in age groups that were not vaccine-eligible. Conclusions: The results from this review demonstrate that PCV7 has had a significant impact on pneumococcal meningitis across all ages through its use in pediatric immunization programs. With the introduction of 13-valent PCV (PCV13) we can expect to see a reduction in the incidence of pneumococcal meningitis due to the six additional serotypes included, as well as continued protection against pneumococcal meningitis due to PCV7 serotypes. Robust surveillance systems are essential for the evaluation of the impact of PCV13 on all-type pneumococcal meningitis and for monitoring the evolution of non-vaccine serotype pneumococcal meningitis. [ABSTRACT FROM AUTHOR]

Background: Public repositories of biological pathways and networks have greatly expanded in recent years. Such databases contain many pathways that facilitate the analysis of high-throughput experimental work and the formulation of new biological hypotheses to be tested, a fundamental principle of the systems biology approach. However, large-scale molecular maps are not always easy to mine and interpret. Results: We have developed BiNoM (Biological Network Manager), a Cytoscape plugin, which provides functions for the import-export of some standard systems biology file formats (import from CellDesigner, BioPAX Level 3 and CSML; export to SBML, CellDesigner and BioPAX Level 3), and a set of algorithms to analyze and reduce the complexity of biological networks. BiNoM can be used to import and analyze files created with the CellDesigner software. BiNoM provides a set of functions allowing to import BioPAX files, but also to search and edit their content. As such, BiNoM is able to efficiently manage large BioPAX files such as whole pathway databases (e.g. Reactome). BiNoMalso implements a collection of powerful graph-based functions and algorithms such as path analysis, decomposition by involvement of an entity or cyclic decomposition, subnetworks clustering and decomposition of a large network in modules. Conclusions: Here, we provide an in-depth overview of the BiNoM functions, and we also detail novel aspects such as the support of the BioPAX Level 3 format and the implementation of a new algorithm for the quantification of pathways for influence networks. At last, we illustrate some of the BiNoM functions on a detailed biological case study of a network representing the G1/S transition of the cell cycle, a crucial cellular process disturbed in most human tumors. [ABSTRACT FROM AUTHOR]

Introduction: Streptococcus pneumoniae can cause invasive pneumococcal diseases (IPD), such as bacteremic pneumonia, bacteremia, meningitis, and sepsis, and non-IPDs, such as otitis media, nonbacteremic pneumonia, and upper respiratory tract infections. It was estimated in 2000 that, worldwide, S. pneumoniae was responsible for 826,000 deaths annually in children aged between 1 month and 5 years. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the USA and in 2001 in Europe. Methods: A literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal morbidity and mortality. Here, the impact on IPD is reported. Results: A total of 37 articles reporting impact data on IPD were included in this review: four from Australia, 17 from western Europe, and 16 from North America. In vaccine-eligible children in the postvaccination period, a reduction ranging from 39.9% in Spain to 99.1% in the USA in vaccine-type (VT) IPD incidence, compared with the prevaccination period, was reported in 18 studies. All but one of the 30 studies assessing the impact of PCV7 on all-type IPD reported a reduction ranging from 1.7% in Spain to 76.3% in Australia. In addition, the majority of studies reported reductions in VT and all-type IPD incidence in age groups that were not vaccine eligible. Conclusions: The results from this review illustrate that PCV7 has had a significant impact on IPD across all ages through its use in pediatric immunization programs. With the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) further reductions in the incidence of IPD due to the six additional serotypes included, as well as continued protection against IPD due to PCV7 serotypes may be expected. Robust surveillance systems are essential for the evaluation of the impact of PCV13 on all-type IPD and for monitoring the evolution of non-VT IPD. [ABSTRACT FROM AUTHOR]

Copyright of Orthodontie Française is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: After the implementation of 7-valent pneumococcal conjugate vaccine (PCV7), in several countries, serotype 19A is now the serotype most frequently involved in pneumococcal diseases and carriage. To determine factors potentially related to 19A nasopharyngeal (NP) carriage we analyzed data from an ongoing prospective French national surveillance study of pneumococcal NP carriage in young children. Methods: NP swabs were obtained from children aged 6 to 24 months, either during routine check-ups with normal findings, or when they presented with acute otitis media (AOM). The swabs were sent for analysis to the French National Reference Centre for Pneumococci. Factors influencing pneumococcal carriage and carriage of penicillin non-susceptible (PNSP), 19A and PNS-19A were investigated by multivariate logistic regression. Results: From 2006 to 2009, 66 practitioners enrolled 3507 children (mean age 13.6 months), of whom, 98.3% of children had been vaccinated with PCV7 and 33.4% of children attended daycare centres (DCC). Serotype 19A was found in 10.4% of the overall population, 20.5% of S. pneumoniae carriers (n = 1780) and 40.8% of PNSP carriers (n = 799). Among 19A strains, 10.7% were penicillin-susceptible, 80% intermediate and 9.3% fully resistant. Logistic regression analysis showed that the main factors associated with PNSP carriage were AOM (OR = 3.09, 95% CI [2.39;3.98]), DCC (OR = 1.70, 95% CI [1.42;2.03]), and recent antibiotic use (OR = 1.24, 95% CI [1.05;1.47]. The main factors predictive of 19A carriage were recent antibiotic use (OR = 1.81, 95% CI [1.42;2.30]), AOM (OR = 1.67, 95% CI [1.11;2.49]), DCC (OR = 1.56, 95% CI [1.21;2.2] and young age, <12 months (OR = 1.51, 95% CI [1.16;1.97]). Conclusion: In a population of children aged from 6 to 24 months with a high rate of PCV7 vaccination coverage, we found that antibiotic exposure, DCC attendance and AOM were linked to 19A carriage. [ABSTRACT FROM AUTHOR]

Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1). We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic approaches to explore these and other aspects of brown algal biology further. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small RNAs that recognize and regulate mRNA target genes. Multiple lines of evidence indicate that they are key regulators of numerous critical functions in development and disease, including cancer. However, defining the place and function of miRNAs in complex regulatory networks is not straightforward. Systems approaches, like the inference of a module network from expression data, can help to achieve this goal. Methodology/Principal Findings: During the last decade, much progress has been made in the development of robust and powerful module network inference algorithms. In this study, we analyze and assess experimentally a module network inferred from both miRNA and mRNA expression data, using our recently developed module network inference algorithm based on probabilistic optimization techniques. We show that several miRNAs are predicted as statistically significant regulators for various modules of tightly co-expressed genes. A detailed analysis of three of those modules demonstrates that the specific assignment of miRNAs is functionally coherent and supported by literature. We further designed a set of experiments to test the assignment of miR-200a as the top regulator of a small module of nine genes. The results strongly suggest that miR-200a is regulating the module genes via the transcription factor ZEB1. Interestingly, this module is most likely involved in epithelial homeostasis and its dysregulation might contribute to the malignant process in cancer cells. Conclusions/Significance: Our results show that a robust module network analysis of expression data can provide novel insights of miRNA function in important cellular processes. Such a computational approach, starting from expression data alone, can be helpful in the process of identifying the function of miRNAs by suggesting modules of co-expressed genes in which they play a regulatory role. As shown in this study, those modules can then be tested experimentally to further investigate and refine the function of the miRNA in the regulatory network. [ABSTRACT FROM AUTHOR]

We investigated nasopharyngeal carriage of Streptococcus pneumoniae and Staphylococcus aureus among infants and young children with acute otitis media in a country where use of 7-valent pneumococcal conjugate vaccine (PCV7) has been progressively implemented. Among 1783 children enrolled, 60.8% carried S. pneumoniae, and 9% carried S. aureus. Among S. pneumoniae carriers, the rate of S. aureus carriage was 8.4%, compared with 9.9% among S. pneumoniae noncarriers. The rate of S. pneumoniae carriage in the PCV7-vaccinated population was lower (59.8%) than that observed in the nonvaccinated population (66.2%; P < .04). In contrast, in young children (age, <2 years) with acute otitis media, our study suggests that the S. aureus carriage rate is not affected by PCV7 immunization (9.0% in vaccinated children vs. 8.7% in nonvaccinated children). Furthermore, in children aged >1 year, the booster dose induces a sharp reduction in the carriage of vaccine serotypes of S. pneumoniae, without any change in S. aureus carriage. [ABSTRACT FROM AUTHOR]

Active anti-HIV therapy can induce hypertriglyceridemia, low high-density lipoprotein (HDL) and insulin resistance, eventually accompanied by clinical lipodystrophy, associated loss of subcutaneous adipose tissue and an increase in abdominal adiposity. The frequency of these metabolic disorders is approximately 50% and host genetic factors might confer particular susceptibility. Variants of apolipoproteins (apo) A5 and C3, interacting with APOE genotypes, have been associated with the severity of antiretroviral therapy-induced dyslipidemia and with occurrence of lipodystrophy, and for APOC3, with objective criteria of fat redistribution. Genetic polymorphisms of the nuclear transcription-factor sterol response element-binding proteins ( SREBP1c) and of tumor necrosis factor-α ( TNFα) have yielded contrasting results. Other candidate genes will be explored to define a pharmacogenomic strategy to identify patients at high risk of metabolic disorders upon antiretroviral therapy. Clin Chem Lab Med 2007;45:815–21. [ABSTRACT FROM AUTHOR]

Study Objective. To determine whether discontinuation of stavudine or protease inhibitor therapy improves human immunodeficiency virus (HIV)-related fat distribution in men. Design. Observational, retrospective study consisting of a cross-sectional (part 1) and a longitudinal (part 2) study. Data Source. Medical records from Purpan University Hospital and La Grave University Hospital, Toulouse, France. Subjects. Eighty men with HIV infection treated with antiretrovirals and 151 healthy male controls matched for age. Measurements and Main Results. In part 1, body composition and fat distribution of the HIV-infected men were compared by dual energy x-ray absorptiometry (DEXA) with those of the controls to determine whether body fat distribution is altered in HIV-infected men. In part 2, we analyzed modifications of body composition and fat distribution in 45 of the 80 patients. These 45 had been exposed to antiretroviral drugs, including stavudine and a protease inhibitor, for at least 5 months before the first of two DEXA assessments. They received three different treatment strategies for several months. In group 1, stavudine was withdrawn; in group 2, protease inhibitor was discontinued, and in group 3, stavudine plus protease inhibitor were continued. Group 1 showed a significant fat gain in the lower extremities 31.7 ± 5.9 months after stavudine discontinuation (p<0.0001). Group 2 did not show any significant modification of total body, lower limb, or trunk fat despite protease inhibitor discontinuation for 35.2 ± 6.6 months. Findings were similar for group 3, who continued receiving stavudine-protease inhibitor therapy for 21.2 ± 12.8 months. Conclusion. These data suggest that long-term withdrawal of stavudine from the antiretroviral therapy regimen may be associated with significant improvement in lipoatrophy in the lower extremities, whereas long-term protease inhibitor withdrawal did not modify fat distribution. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are an extensive class of tiny RNA molecules that regulate the expression of target genes by means of complementary base pair interactions. Although the first miRNAs were discovered in Caenorhabditis elegans, > 300 miRNAs were recently documented in animals and plants, both by cloning methods and computational predictions. We present a genome-wide computational approach to detect miRNA genes in the Arabidopsis thaliana genome. Our method is based on the conservation of short sequences between the genomes of Arabidopsis and rice (Oryza sativa) and on properties of the secondary structure of the miRNA precursor. The method was fine-tuned to take into account plant- specific properties, such as the variable length of the miRNA precursor sequences. In total, 91 potential miRNA genes were identified, of which 58 had at least one nearly perfect match with an Arabidopsis mRNA, constituting the potential targets of those miRNAs. In addition to already known transcription factors involved in plant development the targets also comprised genes involved in several other cellular processes, such as sulfur assimilation and ubiquitin-dependent protein degradation. These findings considerably broaden the scope of miRNA functions in plants. [ABSTRACT FROM AUTHOR]

Presents a study which examined a survey of imported dengue fever in university hospitals in France. Patients and methods; Results; Discussion.

A randomized, open-label trial was performed to study virological and intracellular interactions between stavudine and ribavirin in 30 patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Patients were randomized to receive either interferon and ribavirin or no treatment for HCV infection for 3 months. Intracellular peripheral blood mononuclear cells' stavudine-triphosphate (TP) concentrations were assessed. Plasma HIV RNA levels did not change significantly between baseline and month 3. There was a nonstatistically significant trend for a lower median residual concentration of intracellular stavudine-TP in the treated group, compared with the control group. The same trend was also observed for peak concentrations. Coprescription of ribavirin and stavudine has no short-term impact on plasma HIV RNA level in HIV-HCV-coinfected patients treated with stavudine as a part of their antiretroviral treatment; this coprescription can be safely used, although an in vivo interaction between ribavirin and stavudine is possible. [ABSTRACT FROM AUTHOR]

Reports on the case of a male expatriate with plasmodium falciparum whose neurologic side effects were successfully treated after exposure to two courses of artemether. Clinical manifestations; Result of the neurological examination.

Targeted therapies interfering with specifically one protein activity are promising strategies in the treatment of diseases like cancer. However, accumulated empirical experience has shown that targeting multiple proteins in signaling networks involved in the disease is often necessary. Thus, one important problem in biomedical research is the design and prioritization of optimal combinations of interventions to repress a pathological behavior, while minimizing side-effects. OCSANA (optimal combinations of interventions from network analysis) is a new software designed to identify and prioritize optimal and minimal combinations of interventions to disrupt the paths between source nodes and target nodes. When specified by the user, OCSANA seeks to additionally minimize the side effects that a combination of interventions can cause on specified off-target nodes. With the crucial ability to cope with very large networks, OCSANA includes an exact solution and a novel selective enumeration approach for the combinatorial interventions’ problem.Availability: The latest version of OCSANA, implemented as a plugin for Cytoscape and distributed under LGPL license, is available together with source code at http://bioinfo.curie.fr/projects/ocsana.Supplementary information: Supplementary data are available at Bioinformatics online.Contact: paola.vera-licona@curie.fr [ABSTRACT FROM PUBLISHER]

Summary: We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Bone infection is a common issue in infectiology. The goid standard for evaluating bone infection is the white blood cell (WBC) scan. In our practice the WBC scan is coupied with a bone scan. Discordances in the results of these two examinations are a common occurrence in daily practice. We decided to investigate the meaning of these discordances. Materials and methods: Two hundred and ninety-six 99mTcHMPAO-labelled white blood cells (WBC) and 99mTc-HMDP bone scanning (BS) examinations were performed in our department between 1997 and 2003 for evaluation of bone infection. Out of these 296 examinations, a first rating extracted 54 scans that were considered discordant. These 54 scans were reviewed by three observers. Ciinical and paraciinicai data were obtained for all the cases definitely considered as discordant by all three observers. RESULTS: The observers finally retained-18 cases as discordant from the initiai 296 (6.1%). Thirteen patients were not infected, and five patients were considered infected based on ciinical follow-up or bacterioiogicai and histologicai data. For the 17 patients with WBC-, BS-^, 4 (23.5%) were infected. CONCLUSION: Our study shows that in the vast majority (17 out of 18), discordances consist of a negative WBC scan with a positive bone scan. In these cases the accuracy of the WBC scan is diminished as 23.5% ofthe patients with a negative WBC and a positive bone scan are infected. [ABSTRACT FROM AUTHOR]

High-throughput RNA-sequencing has become the gold standard method for whole-transcriptome gene expression analysis, and is widely used in numerous applications to study cell and tissue transcriptomes. It is also being increasingly used in a number of clinical applications, including expression profiling for diagnostics and alternative transcript detection. However, despite its many advantages, RNA sequencing can be challenging in some situations, for instance in cases of low input amounts or degraded RNA samples. Several protocols have been proposed to overcome these challenges, and many are available as commercial kits. In this study, we systematically test three recent commercial technologies for RNA-seq library preparation (TruSeq, SMARTer and SMARTer Ultra-Low) on human biological reference materials, using standard (1 mg), low (100 ng and 10 ng) and ultra-low (<1 ng) input amounts, and for mRNA and total RNA, stranded and unstranded. The results are analyzed using read quality and alignment metrics, gene detection and differential gene expression metrics. Overall, we show that the TruSeq kit performs well with an input amount of 100 ng, while the SMARTer kit shows decreased performance for inputs of 100 and 10 ng, and the SMARTer Ultra-Low kit performs relatively well for input amounts <1 ng. All the results are discussed in detail, and we provide guidelines for biologists for the selection of an RNA-seq library preparation kit. [ABSTRACT FROM AUTHOR]

Background: HIV-infected patients starting antiretroviral treatment (ART) experience deep and early disorders in fat and bone metabolism, leading to concomitant changes in fat mass and bone mineral density.Methods: We conducted a prospective study in treatment-naive HIV-infected patients randomized to receive two nucleoside reverse transcriptase inhibitors in combination with either a protease inhibitor (PI) or a non-nucleosidic reverse transcriptase inhibitor (NNRTI), to evaluate early changes in body composition, bone mineral density and metabolic markers as differentially induced by antiretroviral therapies. We measured changes in markers of carbohydrate, of fat and bone metabolism, and, using dual-emission X-ray absorptiometry (DXA), body composition and bone mineral density (BMD). Complete data on changes between baseline and after 21 months treatment were available for 35 patients (16 in the PI group and 19 in the NNRTI group).Results: A significant gain in BMI and in total and lower limb fat mass was recorded only in patients receiving PI. A loss of lumbar BMD was observed in both groups, being higher with PI. Plasma markers of bone metabolism (alkaline phosphatase, osteocalcin, collagen crosslaps) and levels of parathormone and of 1,25diOH-vitamin D3 significantly increased in both groups, concomitant with a decline in 25OH-vitamin D3. Lipids and glucose levels increased in both groups but rise in triglyceride was more pronounced with PI. A correlation between loss of BMD and gain of fat mass is observed in patients starting PI.Conclusions: We evidenced an early effect of ART on lipid and bone metabolisms. PI lead to a significant gain in fat mass correlated with a sharp drop in BMD but active bone remodelling is evident with all antiretroviral treatments, associated with low vitamin D levels and hyperparathyroidism. In parallel, signs of metabolic restoration are evident. However, early increases in lean and fat mass, triglycerides, waist circumference and leptin are much more pronounced with PI. [ABSTRACT FROM AUTHOR]

Motivation: Cancer is a complex disease, triggered by mutations in multiple genes and pathways. There is a growing interest in the application of systems biology approaches to analyze various types of cancer-related data to understand the overwhelming complexity of changes induced by the disease. Results: We reconstructed a regulatory module network using gene expression, microRNA expression and a clinical parameter, all measured in lymphoblastoid cell lines derived from patients having aggressive or non-aggressive forms of prostate cancer. Our analysis identified several modules enriched in cell cycle-related genes as well as novel functional categories that might be linked to prostate cancer. Almost one-third of the regulators predicted to control the expression levels of the modules are microRNAs. Several of them have already been characterized as causal in various diseases, including cancer. We also predicted novel microRNAs that have never been associated to this type of tumor. Furthermore, the condition-dependent expression of several modules could be linked to the value of a clinical parameter characterizing the aggressiveness of the prostate cancer. Taken together, our results help to shed light on the consequences of aggressive and non-aggressive forms of prostate cancer. [ABSTRACT FROM AUTHOR]