Search results for "Translational"
showing 10 items of 418 documents
Pulmonary vascular endothelium: the orchestra conductor in respiratory diseases
2017
The European Respiratory Society (ERS) Research Seminar entitled “Pulmonary vascular endothelium: orchestra conductor in respiratory diseases - highlights from basic research to therapy” brought together international experts in dysfunctional pulmonary endothelium, from basic science to translational medicine, to discuss several important aspects in acute and chronic lung diseases. This review will briefly sum up the different topics of discussion from this meeting which was held in Paris, France on October 27–28, 2016. It is important to consider that this paper does not address all aspects of endothelial dysfunction but focuses on specific themes such as: 1) the complex role of the pulmon…
Impact of T-cell-mediated immune response on xenogeneic heart valve transplantation: short-term success and mid-term failure.
2017
Objectives Allogeneic frozen cryopreserved heart valves (allografts or homografts) are commonly used in clinical practice. A major obstacle for their application is the limited availability in particular for paediatrics. Allogeneic large animal studies revealed that alternative ice-free cryopreservation (IFC) results in better matrix preservation and reduced immunogenicity. The objective of this study was to evaluate xenogeneic (porcine) compared with allogeneic (ovine) IFC heart valves in a large animal study. Methods IFC xenografts and allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks. Immunohistochemistry, ex vivo computed tomography scans and transforming growth fa…
News from the Underground: What were the most important scientific/clinical take-home messages for juniors?
2014
The ERS International Congress has traditionally been a splendid opportunity to present current updates in clinical respiratory medicine and new research findings. This year’s programme was packed, making it impossible to attend all sessions, but juniors interested in specific fields were there for you to highlight the most important take home messages from the 2014 ERS International Congress in Munich. Amongst the most important news for the clinicians was the publication of a Global Initiative for Asthma (GINA) guidelines update [1]. In the updated guidelines, the heterogeneity of asthma is emphasised, suggesting the need of “4P” (Personalised, Predictive, Preventive and Participatory) tr…
Molecular Mediators of RNA Loading into Extracellular Vesicles
2021
In the last decade, an increasing number of studies have demonstrated that non-coding RNA (ncRNAs) cooperate in the gene regulatory networks with other biomolecules, including coding RNAs, DNAs and proteins. Among them, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are involved in transcriptional and translation regulation at different levels. Intriguingly, ncRNAs can be packed in vesicles, released in the extracellular space, and finally internalized by receiving cells, thus affecting gene expression also at distance. This review focuses on the mechanisms through which the ncRNAs can be selectively packaged into extracellular vesicles (EVs).
Strategies for annotation and curation of translational databases: the eTUMOUR project
2012
Altres ajuts: LSHC/CT2004-503094 The eTUMOUR (eT) multi-centre project gathered in vivo and ex vivo magnetic resonance (MR) data, as well as transcriptomic and clinical information from brain tumour patients, with the purpose of improving the diagnostic and prognostic evaluation of future patients. In order to carry this out, among other work, a database-the eTDB-was developed. In addition to complex permission rules and software and management quality control (QC), it was necessary to develop anonymization, processing and data visualization tools for the data uploaded. It was also necessary to develop sophisticated curation strategies that involved on one hand, dedicated fields for QC-gene…
Atomic teleportation via cavity QED and position measurements: efficiency analysis
2008
We have recently presented a novel protocol to teleport an unknown atomic state via cavity QED and position measurements. Here, after a brief review of our scheme, we provide a quantitative study of its efficiency. This is accomplished by an explicit description of the measurement process that allows us to derive the fidelity with respect to the atomic internal state to be teleported.
Determinants of intracellular RNA pharmacokinetics: Implications for RNA-based immunotherapeutics
2011
RNAs with optimized properties are increasingly investigated as a tool to deliver the genetic information of complete antigens into professional antigen-presenting dendritic cells for HLA haplotype-independent antigen-specific vaccination against cancer. As the dose of the antigen and duration of its presentation are critical factors for generating strong and sustained antigen-specific immune responses, improvement of the immunobioavailability of RNA-based vaccines has been a recurrent subject of research. Substantial increase of the amount of antigen produced from RNA can be achieved by optimizing RNA stability and translational efficiency. Both features are determined by cis-acting elemen…
mRNA as a versatile tool for exogenous protein expression.
2012
Several viral and non-viral vectors have been developed for exogenous protein expression in specific cells. Conventionally, this purpose is achieved through the use of recombinant DNA. But mainly due to the risks associated with permanent genetic alteration of cells, safety and ethical concerns have been raised for the use of DNA-based vectors in human clinical therapy. In the last years, synthetic messenger RNA has emerged as powerful tool to deliver genetic information. RNA vectors exhibit several advantages compared to DNA and are particularly interesting for applications that require transient gene expression. RNA stability and translation efficiency can be increased by cis-acting struc…
Synthetic mRNAs with Superior Translation and Stability Properties
2012
The translational efficiency and stability of synthetic mRNA in both cultured cells and whole animals can be improved by incorporation of modified cap structures at the 5'-end. mRNAs are synthesized in vitro by a phage RNA polymerase transcribing a plasmid containing the mRNA sequence in the presence of all four NTPs plus a cap dinucleotide. Modifications in the cap dinucleotide at the 2'- or 3'-positions of m(7)Guo, or modifications in the polyphosphate chain, can improve both translational efficiency and stability of the mRNA, thereby increasing the amount and duration of protein expression. In the context of RNA-based immunotherapy, the latter is especially important for antigen producti…
Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune r…
2010
Vaccination with in vitro transcribed RNA coding for tumor antigens is considered a promising approach for cancer immunotherapy and has already entered human clinical testing. One of the basic objectives for development of RNA as a drug is the optimization of immunobioavailability of the encoded antigen in vivo. By analyzing the effect of different synthetic 5' mRNA cap analogs on the kinetics of the encoded protein, we found that m(2)(7,2'-O)Gpp(S)pG (beta-S-ARCA) phosphorothioate caps, in particular the D1 diastereoisomer, profoundly enhance RNA stability and translational efficiency in immature but not mature dendritic cells. Moreover, in vivo delivery of the antigen as beta-S-ARCA(D1)-c…