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Guillaume Desoubeaux, Janice M Reichert, Matthew Sleeman, Karen L Reckamp, Bernhard Ryffel, Jörg P Adamczewski, Theresa D Sweeney, Rita Vanbever, Patrice Diot, Caroline A Owen, Clive Page, Stéphanie Lerondel, Alain Le Pape, Nathalie Heuze-Vourc'h
Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence "MAbImprove," the GDR 3260 "Antibodies and therapeutic targeting," and the Grant Research program ARD2020 "Biotherapeutics" invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 - April 1, 2016 in Tours, France...
August 2016: MAbs
Maria Francesca Spadea, Aurora Fassi, Paolo Zaffino, Marco Riboldi, Guido Baroni, Nicolas Depauw, Joao Seco
PURPOSE: To obtain a contrasted image of the tumor region during the setup for proton therapy in lung patients, by using proton radiography and x-ray computed tomography (CT) prior knowledge. METHODS AND MATERIALS: Six lung cancer patients' CT scans were preprocessed by masking out the gross tumor volume (GTV), and digitally reconstructed radiographs along the planned beam's eye view (BEV) were generated, for a total of 27 projections. Proton radiographies (PR) were also computed for the same BEV through Monte Carlo simulations...
November 1, 2014: International Journal of Radiation Oncology, Biology, Physics
Karolina Michalska, Gekleng Chhor, Shonda Clancy, Robert Jedrzejczak, Gyorgy Babnigg, Stephen C Winans, Andrzej Joachimiak
UNLABELLED: Burkholderia cepacia complex is a set of closely related bacterial species that are notorious pathogens of cystic fibrosis patients, responsible for life-threatening lung infections. Expression of several virulence factors of Burkholderia cepacia complex is controlled by a mechanism known as quorum sensing (QS). QS is a means of bacterial communication used to coordinate gene expression in a cell-density-dependent manner. The system involves the production of diffusible signaling molecules (N-acyl-l-homoserine lactones, AHLs), that bind to cognate transcriptional regulators and influence their ability to regulate gene expression...
September 2014: FEBS Journal
Jian Woon Chen, Chong-Lek Koh, Choon-Kook Sam, Wai-Fong Yin, Kok-Gan Chan
In the bacteria kingdom, quorum sensing (QS) is a cell-to-cell communication that relies on the production of and response to specific signaling molecules. In proteobacteria, N-acylhomoserine lactones (AHLs) are the well-studied signaling molecules. The present study aimed to characterize the production of AHL of a bacterial strain A9 isolated from a Malaysian tropical soil. Strain A9 was identified as Burkholderia sp. using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry and 16S rDNA nucleotide sequence analysis...
2013: Sensors
Sujatha Subramoni, Pamela A Sokol
Burkholderia cepacia complex strains communicate using N-acyl homoserine lactones and BDSF-dependent quorum sensing (QS) systems. Burkholderia cenocepacia QS systems include CepIR, CciIR, CepR2 and BDSF. Analysis of CepR, CciIR, CepR2 and RpfF (BDSF synthase) QS regulons revealed that these QS systems both independently regulate and coregulate many target genes, often in an opposing manner. The role of QS and several QS-regulated genes in virulence has been determined using vertebrate, invertebrate and plant infection models...
December 2012: Future Microbiology
Brian J Simonds, Archana Subramaniyan, Ryan O'Hayre, P Craig Taylor
A technique for determining the size of metallic nanoparticles incorporated into a ceramic is demonstrated using conduction electron paramagnetic resonance (CEPR). The resonances associated with palladium nanoparticles in a perovskite material are identified and studied as a function of temperature. As this line shape changes with temperature, the point at which the skin depth of the palladium is the same as the size of the nanoparticles is clearly identified due to a microwave saturation effect. This allows for a determination of their average size, which, in this case is 75±20nm...
December 2012: Journal of Magnetic Resonance
Gina T Ryan, Yuping Wei, Stephen C Winans
Burkholderia cenocepacia is an opportunistic human pathogen that encodes two LuxI-type acylhomoserine lactone (AHL) synthases and three LuxR-type AHL receptors. Of these, cepI and cepR form a cognate synthase/receptor pair, as do cciI and cciR, while cepR2 lacks a genetically linked AHL synthase gene. Another group showed that a cepR2 mutant overexpressed a cluster of linked genes that appear to direct the production of a secondary metabolite. We found that these same genes were upregulated by octanoylhomoserine lactone (OHL), which is synthesized by CepI...
January 2013: Molecular Microbiology
Stephan Schwager, Kirsty Agnoli, Manuela Köthe, Friederike Feldmann, Michael Givskov, Aurelien Carlier, Leo Eberl
Burkholderia cenocepacia H111, a strain isolated from a cystic fibrosis patient, has been shown to effectively kill the nematode Caenorhabditis elegans. We used the C. elegans model of infection to screen a mini-Tn5 mutant library of B. cenocepacia H111 for attenuated virulence. Of the approximately 5,500 B. cenocepacia H111 random mini-Tn5 insertion mutants that were screened, 22 showed attenuated virulence in C. elegans. Except for the quorum-sensing regulator cepR, none of the mutated genes coded for the biosynthesis of classical virulence factors such as extracellular proteases or siderophores...
January 2013: Infection and Immunity
Silja Inhülsen, Claudio Aguilar, Nadine Schmid, Angela Suppiger, Kathrin Riedel, Leo Eberl
Burkholderia cenocepacia has emerged as an important pathogen for patients suffering from cystic fibrosis (CF). Previous work has shown that this organism employs the CepIR quorum-sensing (QS) system to control the expression of virulence factors as well as the formation of biofilms. To date, however, very little is known about the QS-regulated virulence factors and virtually nothing about the factors that link QS and biofilm formation. Here, we have employed a combined transcriptomic and proteomic approach to precisely define the QS regulon in our model strain B...
June 2012: MicrobiologyOpen
Eoin P O'Grady, Duber F Viteri, Pamela A Sokol
Burkholderia cenocepacia causes chronic and life-threatening respiratory infections in immunocompromized people. The B. cenocepacia N-acyl-homoserine lactone (AHL)-dependent quorum sensing system relies on the production of AHLs by the synthases CepI and CciI while CepR, CciR and CepR2 control expression of many genes important for pathogenesis. Downstream from, and co-transcribed with cepI, lies BCAM1871 encoding a hypothetical protein that was uncharacterized prior to this study. Orthologs of B. cenocepacia BCAM1871 are uniquely found in Burkholderia spp and are conserved in their genomic locations in pathogenic Burkholderia...
2012: PloS One
Christian G Ramos, Sílvia A Sousa, André M Grilo, Joana R Feliciano, Jorge H Leitão
Burkholderia cenocepacia J2315 is a highly virulent and epidemic clinical isolate of the B. cepacia complex (Bcc), a group of bacteria that have emerged as important pathogens to cystic fibrosis patients. This bacterium, together with all Bcc strains and a few other prokaryotes, is unusual for encoding in its genome two distinct and functional Hfq-like proteins. In this work, we show results indicating that the 188-amino-acid Hfq2 protein is required for the full virulence and stress resistance of B. cenocepacia J2315, despite the presence on its genome of the functional 79-amino-acid Hfq protein encoded by the hfq gene...
April 2011: Journal of Bacteriology
Yuping Wei, Gina T Ryan, Ana L Flores-Mireles, Esther D Costa, David J Schneider, Stephen C Winans
Burkholderia cenocepacia is an opportunistic pathogen of humans that encodes two genes that resemble the acylhomoserine lactone synthase gene luxI of Vibrio fischeri and three genes that resemble the acylhomoserine lactone receptor gene luxR. Of these, CepI synthesizes octanoylhomoserine lactone (OHL), while CepR is an OHL-dependent transcription factor. In the current study we developed a strategy to identify genes that are directly regulated by CepR. We systematically altered a CepR binding site (cep box) upstream of a target promoter to identify nucleotides that are essential for CepR activity in vivo and for CepR binding in vitro...
February 2011: Molecular Microbiology
Suzanne A McKeon, David T Nguyen, Duber F Viteri, James E A Zlosnik, Pamela A Sokol
Quorum sensing (QS) contributes to the virulence of Pseudomonas aeruginosa and Burkholderia cepacia complex lung infections. P. aeruginosa QS mutants are frequently isolated from patients with cystic fibrosis. The objective of this study was to determine whether similar adaptations occur over time in B. cepacia complex isolates. Forty-five Burkholderia multivorans and Burkholderia cenocepacia sequential isolates from patients with cystic fibrosis were analyzed for N-acyl-homoserine lactone activity. All but one isolate produced N-acyl-homoserine lactones...
February 1, 2011: Journal of Infectious Diseases
Eoin P O'Grady, David T Nguyen, Laure Weisskopf, Leo Eberl, Pamela A Sokol
Burkholderia cenocepacia is a significant opportunistic pathogen in individuals with cystic fibrosis. ShvR, a LysR-type transcriptional regulator, has previously been shown to influence colony morphology, biofilm formation, virulence in plant and animal infection models, and some quorum-sensing-dependent phenotypes. In the present study, it was shown that ShvR negatively regulates its own expression, as is typical for LysR-type regulators. The production of quorum-sensing signal molecules was detected earlier in growth in the shvR mutant than in the wild type, and ShvR repressed expression of the quorum-sensing regulatory genes cepIR and cciIR...
January 2011: Journal of Bacteriology
James E A Zlosnik, David P Speert
Bacteria of the Burkholderia cepacia complex (BCC) are associated with severe infection in cystic fibrosis. Recent evidence shows that the mucoid phenotype is common in BCC bacteria; however, during chronic infection, transitions from the mucoid to nonmucoid morphology have been shown to take place. Here we use RNA microarray and proteomic isobaric tagging relative and absolute quantitation technologies to gain insight into a pair of mucoid and nonmucoid isolates of B. cenocepacia obtained from a chronically infected patient with cystic fibrosis in the year prior to her death...
September 1, 2010: Journal of Infectious Diseases
Annette C Vergunst, Annemarie H Meijer, Stephen A Renshaw, David O'Callaghan
Bacteria belonging to the "Burkholderia cepacia complex" (Bcc) often cause fatal pulmonary infections in cystic fibrosis patients, yet little is know about the underlying molecular mechanisms. These Gram-negative bacteria can adopt an intracellular lifestyle, although their ability to replicate intracellularly has been difficult to demonstrate. Here we show that Bcc bacteria survive and multiply in macrophages of zebrafish embryos. Local dissemination by nonlytic release from infected cells was followed by bacteremia and extracellular replication...
April 2010: Infection and Immunity
Eoin P O'Grady, Duber F Viteri, Rebecca J Malott, Pamela A Sokol
BACKGROUND: Burkholderia cenocepacia belongs to a group of closely related organisms called the B. cepacia complex (Bcc) which are important opportunistic human pathogens. B. cenocepacia utilizes a mechanism of cell-cell communication called quorum sensing to control gene expression including genes involved in virulence. The B. cenocepacia quorum sensing network includes the CepIR and CciIR regulatory systems. RESULTS: Global gene expression profiles during growth in stationary phase were generated using microarrays of B...
2009: BMC Genomics
Zélia Zilda Lourenço de Camargo Bittencourt, Eduardo Luiz Hoehne
The aim of this study was to assess the quality of life of deaf people's relatives in a rehabilitation service. This descriptive study was conducted from March to June 2005 and a sample of fifteen parents of deaf people assisted in CEPRE/FCM/UNICAMP was interviewed. It was used a Portuguese version of the generic instrument of quality of life assessment WHOQOL--BREF (World Health Organization Quality of Life), along with an identification questionnaire and socio-demographic data. The SPSS program was used in the statistics analysis, with the scores transformed from zero to 100...
July 2009: Ciência & Saúde Coletiva
Silvia Schmidt, Judith F Blom, Jakob Pernthaler, Gabriele Berg, Adam Baldwin, Eshwar Mahenthiralingam, Leo Eberl
Members of the genus Burkholderia are known for their ability to suppress soil-borne fungal pathogens by the production of various antibiotic compounds. In this study we investigated the role of N-acylhomoserine lactone (AHL)-dependent quorum sensing (QS) in the expression of antifungal traits. Using a quorum quenching approach, that is, by heterologous expression of the Bacillus sp. AiiA lactonase, we show that expression of antifungal activities is AHL-dependent in the large majority of the investigated strains belonging to various Burkholderia species...
June 2009: Environmental Microbiology
Dong Wang, Ming Lu, Jing Miao, Tingting Li, Edwin Wang, Qinghua Cui
Identifying the tissues in which a microRNA is expressed could enhance the understanding of the functions, the biological processes, and the diseases associated with that microRNA. However, the mechanisms of microRNA biogenesis and expression remain largely unclear and the identification of the tissues in which a microRNA is expressed is limited. Here, we present a machine learning based approach to predict whether an intronic microRNA show high co-expression with its host gene, by doing so, we could infer the tissues in which a microRNA is high expressed through the expression profile of its host gene...
2009: PloS One
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