HyperLEDA. III. The catalogue of extragalactic distances

We present the compilation catalogue of redshift-independent distances included in the HyperLEDA database. It is actively maintained to be up-to-date, and the current version counts 6640 distance measurements for 2335 galaxies compiled from 430 published articles. Each individual series is recalibrated onto a common distance scale based on a carefully selected set of high-quality measurements. This information together with data on HI line-width, central velocity dispersion, magnitudes, diameters, and redshift is used to derive a homogeneous distance estimate and physical properties of galaxies, such as their absolute magnitudes and intrinsic size.Comment: accepted to A&

The protective role of transferrin in Müller glial cells after iron-induced toxicity

PURPOSE: Transferrin (Tf) expression is enhanced by aging and inflammation in humans. We investigated the role of transferrin in glial protection. METHODS: We generated transgenic mice (Tg) carrying the complete human transferrin gene on a C57Bl/6J genetic background. We studied human (hTf) and mouse (mTf) transferrin localization in Tg and wild-type (WT) C57Bl/6J mice using immunochemistry with specific antibodies. Müller glial (MG) cells were cultured from explants and characterized using cellular retinaldehyde binding protein (CRALBP) and vimentin antibodies. They were further subcultured for study. We incubated cells with FeCl(3)-nitrilotriacetate to test for the iron-induced stress response; viability was determined by direct counting and measurement of lactate dehydrogenase (LDH) activity. Tf expression was determined by reverse transcriptase-quantitative PCR with human- or mouse-specific probes. hTf and mTf in the medium were assayed by ELISA or radioimmunoassay (RIA), respectively. RESULTS: mTf was mainly localized in retinal pigment epithelium and ganglion cell layers in retina sections of both mouse lines. hTf was abundant in MG cells. The distribution of mTf and hTf mRNA was consistent with these findings. mTf and hTf were secreted into the medium of MG cell primary cultures. Cells from Tg mice secreted hTf at a particularly high level. However, both WT and Tg cell cultures lose their ability to secrete Tf after a few passages. Tg MG cells secreting hTf were more resistant to iron-induced stress toxicity than those no longer secreted hTf. Similarly, exogenous human apo-Tf, but not human holo-Tf, conferred resistance to iron-induced stress on MG cells from WT mice. CONCLUSIONS: hTf localization in MG cells from Tg mice was reminiscent of that reported for aged human retina and age-related macular degeneration, both conditions associated with iron deposition. The role of hTf in protection against toxicity in Tg MG cells probably involves an adaptive mechanism developed in neural retina to control iron-induced stress

EMEA and Gene Therapy Medicinal Products Development in the European Union

The evaluation of quality, safety, and efficacy of medicinal products by the European Medicines Evaluation Agency (EMEA) via the centralized procedure is the only available regulatory procedure for obtaining marketing authorization for gene therapy (GT) medicinal products in the European Union. The responsibility for the authorization of clinical trials remains with the national competent authorities (NCA) acting in a harmonized framework from the scientific viewpoint. With the entry into force of a new directive on good clinical practice implementation in clinical trials as of 1 May 2004, procedural aspects will also be harmonized at EU level. Scientifically sound development of medicinal products is the key for the successful registration of dossiers and for contributing to the promotion and protection of public health. The objective of this paper is to introduce the EMEA regulatory processes and scientific activities relevant to GT medicinal products

Antibiotic-free selection in E. coli: new considerations for optimal design and improved production

<p>Abstract</p> <p>Background</p> <p>The increasing regulatory requirements to which biological agents are subjected will have a great impact in the field of industrial protein expression and production. There is an expectation that in a near future, there may be "zero tolerance" towards antibiotic-based selection and production systems. Besides the antibiotic itself, the antibiotic resistance gene is an important consideration. The complete absence of antibiotic-resistance gene being the only way to ensure that there is no propagation in the environment or transfer of resistance to pathogenic strains.</p> <p>Results</p> <p>In a first step, we have designed a series of vectors, containing a stabilization element allowing a complete elimination of antibiotics during fermentation. Vectors were further improved in order to include alternative selection means such as the well known poison/antidote stabilization system. Eventually we propose an elegant positive pressure of selection ensuring the elimination of the antibiotic-resistance gene through homologous recombination. In addition, we have shown that the presence of an antibiotic resistance gene can indirectly reduce the amount of expressed protein, since even in absence of selection pressure the gene would be transcribed and account for an additional stress for the host during the fermentation process.</p> <p>Conclusions</p> <p>We propose a general strategy combining plasmid stabilization and antibiotic-free selection. The proposed host/vector system, completely devoid of antibiotic resistance gene at the end of construction, has the additional advantage of improving recombinant protein expression and/or plasmid recovery.</p

Global transcriptional control by glucose and carbon regulator CcpA in Clostridium difficile.

International audienceThe catabolite control protein CcpA is a pleiotropic regulator that mediates the global transcriptional response to rapidly catabolizable carbohydrates, like glucose in Gram-positive bacteria. By whole transcriptome analyses, we characterized glucose-dependent and CcpA-dependent gene regulation in Clostridium difficile. About 18% of all C. difficile genes are regulated by glucose, for which 50% depend on CcpA for regulation. The CcpA regulon comprises genes involved in sugar uptake, fermentation and amino acids metabolism, confirming the role of CcpA as a link between carbon and nitrogen pathways. Using combination of chromatin immunoprecipitation and genome sequence analysis, we detected 55 CcpA binding sites corresponding to ∼140 genes directly controlled by CcpA. We defined the C. difficile CcpA consensus binding site (cre(CD) motif), that is, 'RRGAAAANGTTTTCWW'. Binding of purified CcpA protein to 19 target cre(CD) sites was demonstrated by electrophoretic mobility shift assay. CcpA also directly represses key factors in early steps of sporulation (Spo0A and SigF). Furthermore, the C. difficile toxin genes (tcdA and tcdB) and their regulators (tcdR and tcdC) are direct CcpA targets. Finally, CcpA controls a complex and extended regulatory network through the modulation of a large set of regulators

Simulation of orthotic treatment in adolescent idiopathic scoliosis using a subject-specific finite element model

Adolescent idiopathic scoliosis (AIS) is a threedimensional deformity of the spine, often progressing rapidly during the growth spurt. Severe scoliosis can lead to significant degradation of quality of life and functional impairment; the aim of early orthotic treatment is to slow down curvature progression until skeletal maturity. Efficacy of bracing has often been questioned (Negrini et al., 2010; Weinstein et al., 2013), and often relies on the orthotist’s experience since objective methods to design and predict brace action are still in development (Cobetto et al., 2014). A clinically-relevant method for the evaluation of brace simulation in AIS was recently presented (Vergari et al., 2015) and applied to preliminarily validate a finite element model (FEM) of the trunk. The aim of this work was to improve the simulation of brace action on scoliotic trunks and to validate the model on a larger cohor

Early detection of progressive adolescent idiopathic scoliosis : a severity index

Study Design. Early detection of progressive adolescent idiopathic scoliosis (AIS) was assessed based on 3D quantification of the deformity. Objective. Based on 3D quantitative description of scoliosis curves, the aim is to assess a specific deformation pattern that could be an early detectable severity index for progressive AIS. Summary of Background Data. Early detection of progressive scoliosis is important for adapted treatment to limit progression. However, progression risk assessment is mainly based on the follow up, waiting for signs of rapid progression that generally occur during the growth peak. Methods. 65 mild scoliosis (16 boys, 49 girls, Cobb Angle between 10 and 20°) with a Risser between 0 and 2 were followed from their first exam until a decision was made by the clinician, either considering the spine as stable at the end of growth (26 patients) or planning to brace because of progression (39 patients). Calibrated biplanar X-rays were performed and 3D reconstructions of the spine allowed to calculate six local parameters related to main curve deformity. For progressive curve 3D phenotype assessment, data were compared to those previously assessed for 30 severe scoliosis (Cobb Angle > 35°), 17 scoliosis before brace (Cobb Angle > 29°) and 53 spines of non-scoliosis subjects. A predictive discriminant analysis was performed to assess similarity of mild scoliosis curves either to those of scoliosis or non-scoliosis spines, yielding a severity index (S-index). S-index value at first exam was compared to clinical outcome. Results. At the first exam, 53 out of 65 predictions (82%) were in agreement with actual clinical outcome. 89 % of the curves that were predicted as progressive proved accurate Conclusion. Although still requiring large scale validation, results are promising for early detection of progressive curves

Towards a predictive simulation of brace action in adolescent idiopathic scoliosis

The data collection was approved of by the ethical commit-tee (CPP 6001 Ile de France V), and patients and their parents signed an informed consent.Bracing is the most common treatment to stop the progression of adolescent idiopathic scoliosis. Finite element modeling could help improve brace design, but model validation is still a challenge. In this work, the clinical relevance of a predictive and subject-specific model for bracing was evaluated in forty-six AIS patients. The model reproduces brace action and the patient’s spinopelvic adjustments to keep balance. The model simulated 70% or more patients with geometrical parameters within a preselected tolerance level. Although the model simulation of the sagittal plane could be improved, the approach is promising for a realistic and predictive simulation of brace action.The authors are grateful to the ParisTech BiomecAM chair program on subject-specific musculoskeletal modelling (with the support of ParisTech and Yves Cotrel Foundations, Proteor, Société Génerale and Covea). We are also thankful to David Barrie Colridge for his support