MYOD1 involvement in myopathy

[Excerpt] Introduction Myogenic Differentiation 1 (MYOD1) encodes a transcription factor that plays an important role in myogenic determination into mature skeletal muscle [1]. The first loss-of-function mutation of MYOD1 in humans was described in three siblings with perinatal lethal fetal akinesia [2].[...]We thank the individual and family. Funding was provided by The Fonds de recherche du Québec - Santé (FRQS) and Canadian Institutes of Health Research (CIHR) to P.M.C., Fundação para a Ciência e Tecnologia (FCT) with the fellowship SFRH/BD/84650/2010 to F.L. and Groupe Pasteur Mutualité Foundation (GPM Foundation) to M.M.info:eu-repo/semantics/publishedVersio

Shape: automatic conformation prediction of carbohydrates using a genetic algorithm

<p>Abstract</p> <p>Background</p> <p>Detailed experimental three dimensional structures of carbohydrates are often difficult to acquire. Molecular modelling and computational conformation prediction are therefore commonly used tools for three dimensional structure studies. Modelling procedures generally require significant training and computing resources, which is often impractical for most experimental chemists and biologists. <monospace>Shape</monospace> has been developed to improve the availability of modelling in this field.</p> <p>Results</p> <p>The <monospace>Shape</monospace> software package has been developed for simplicity of use and conformation prediction performance. A trivial user interface coupled to an efficient genetic algorithm conformation search makes it a powerful tool for automated modelling. Carbohydrates up to a few hundred atoms in size can be investigated on common computer hardware. It has been shown to perform well for the prediction of over four hundred bioactive oligosaccharides, as well as compare favourably with previously published studies on carbohydrate conformation prediction.</p> <p>Conclusion</p> <p>The <monospace>Shape</monospace> fully automated conformation prediction can be used by scientists who lack significant modelling training, and performs well on computing hardware such as laptops and desktops. It can also be deployed on computer clusters for increased capacity. The prediction accuracy under the default settings is good, as it agrees well with experimental data and previously published conformation prediction studies. This software is available both as open source and under commercial licenses.</p

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

BACKGROUND: Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS). METHODS: Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies). RESULTS: We identified causative mutations in 17 out of the 40 patients (43 %). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV-sensitive syndrome and in two cases with mixed XP/CS phenotypes. CONCLUSIONS: Our study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Abundance and scarcity: classical theories of money, bank balance sheets and business models, and the British restriction of 1797‐1818.

The thesis looks through the lens of bank balance sheet accounting to investigate the structural change in the British banking system between 1780 and 1832, and how classical quantity theorists of money attempted to respond to the ensuing financialisation of the wartime economy with its growing reliance on credit funded with paper-based instruments (the ‘Vansittart system’ of war finance). The thesis combines contributions to three separate fields to construct a holistic historical example of the challenges faced by monetary economists when ‘modelling’ financial innovation, credit growth, ‘fringe’ banking, and agent incentives – at a time of radical experimentation: the suspension of the 80-year-old gold standard (“the Restriction”). First, critical text analysis of the history of economics argues that the 1809-10 debate between Ricardo and Bosanquet at the peak of the credit boom, bifurcated classical theory into two timeless competing policy paradigms advocating the ‘Scarcity’ or ‘Abundance’ of money relative to exchange transactions. The competing hypotheses regarding the role of money and credit are identified and the rest of the thesis examines the archival evidence for each. Second, the core of the thesis contributes to the historical literature on banking in relation to money by reconstructing a taxonomy of bank business models, their relationships with the London inter-bank settlement system, and their responses to the Restriction - drawing on some 17,000 mostly new data points collected from the financial records of London and Country banks. The final section contributes to the economic history of money by constructing aggregated views of total bank liabilities from the firm-level data, scaled to recently available British GDP estimates. These are examined to establish (with hindsight) the relative merits and lacuna of the competing theoretical hypotheses postulated by political economists. It was the period of deleveraging after 1810 that revealed the lacuna of both paradigms

A light-based parametric design model: the application of the inverse lighting in the design of the Louvre Abu Dhabi museum

The use of a design tool materializing the performative design concept is presented. The association of parametric design with lighting intentions leads to a light-based parametric design approach. This approach have been implemented through an inverse natural lighting model which is intended to aid the daylight design (windows, shading devices or others) in the early stages of architectural design. We show this model can be used in a performative design approach to define the transparency property through a case study: the dome of the Louvre Abu Dhabi museum by Ateliers Jean Nouvel

Lighting Intention Materialization with a Light-Based Parametric Design Model

How the inverse lighting methods could help the architectural design? We address this issue with an original light-based parametric design model dedicated to the architectural design. This model associates the parametric design approach with the lighting intentions expressed by the architects. It has been implemented thanks to an inverse lighting technique in a tool intended to aid the design of the windows and the shading devices in the early stages of architectural design. This model is used in a performative design approach onto the dome of the Louvre Abu Dhabi museum in order to define the transparency property of the dome