Whole-exome re-sequencing in a family quartet identifies POP1 mutations as the cause of a novel skeletal dysplasia

Recent advances in DNA sequencing have enabled mapping of genes for monogenic traits in families with small pedigrees and even in unrelated cases. We report the identification of disease-causing mutations in a rare, severe, skeletal dysplasia, studying a family of two healthy unrelated parents and two affected children using whole-exome sequencing. The two affected daughters have clinical and radiographic features suggestive of anauxetic dysplasia (OMIM 607095), a rare form of dwarfism caused by mutations of RMRP. However, mutations of RMRP were excluded in this family by direct sequencing. Our studies identified two novel compound heterozygous loss-of-function mutations in POP1, which encodes a core component of the RNase mitochondrial RNA processing (RNase MRP) complex that directly interacts with the RMRP RNA domains that are affected in anauxetic dysplasia. We demonstrate that these mutations impair the integrity and activity of this complex and that they impair cell proliferation, providing likely molecular and cellular mechanisms by which POP1 mutations cause this severe skeletal dysplasia

Acoustic cardiac triggering: a practical solution for synchronization and gating of cardiovascular magnetic resonance at 7 Tesla

<p>Abstract</p> <p>Background</p> <p>To demonstrate the applicability of acoustic cardiac triggering (ACT) for imaging of the heart at ultrahigh magnetic fields (7.0 T) by comparing phonocardiogram, conventional vector electrocardiogram (ECG) and traditional pulse oximetry (POX) triggered 2D CINE acquisitions together with (i) a qualitative image quality analysis, (ii) an assessment of the left ventricular function parameter and (iii) an examination of trigger reliability and trigger detection variance derived from the signal waveforms.</p> <p>Results</p> <p>ECG was susceptible to severe distortions at 7.0 T. POX and ACT provided waveforms free of interferences from electromagnetic fields or from magneto-hydrodynamic effects. Frequent R-wave mis-registration occurred in ECG-triggered acquisitions with a failure rate of up to 30% resulting in cardiac motion induced artifacts. ACT and POX triggering produced images free of cardiac motion artefacts. ECG showed a severe jitter in the R-wave detection. POX also showed a trigger jitter of approximately Δt = 72 ms which is equivalent to two cardiac phases. ACT showed a jitter of approximately Δt = 5 ms only. ECG waveforms revealed a standard deviation for the cardiac trigger offset larger than that observed for ACT or POX waveforms.</p> <p>Image quality assessment showed that ACT substantially improved image quality as compared to ECG (image quality score at end-diastole: ECG = 1.7 ± 0.5, ACT = 2.4 ± 0.5, p = 0.04) while the comparison between ECG vs. POX gated acquisitions showed no significant differences in image quality (image quality score: ECG = 1.7 ± 0.5, POX = 2.0 ± 0.5, p = 0.34).</p> <p>Conclusions</p> <p>The applicability of acoustic triggering for cardiac CINE imaging at 7.0 T was demonstrated. ACT's trigger reliability and fidelity are superior to that of ECG and POX. ACT promises to be beneficial for cardiovascular magnetic resonance at ultra-high field strengths including 7.0 T.</p

Interactions between Spider Silk and Cells – NIH/3T3 Fibroblasts Seeded on Miniature Weaving Frames

Native spider silk does not require any modification to its application as a biomaterial that can rival any artificial material in terms of cell growth promoting properties. We could show adhesion mechanics on intracellular level. Additionally, proliferation kinetics were higher than in enzymatically digested controls, indicating that spider silk does not require modification. Recent findings concerning reduction of cell proliferation after exposure could not be met. As biotechnological production of the hierarchical composition of native spider silk fibres is still a challenge, our study has a pioneer role in researching cellular mechanics on native spider silk fibres

Contemporary Music and Its Audience: A Tale of Benevolent Asceticism?

International audienceDescriptive statistics on musical consumption from recent surveys on cultural consumption in France show that the typical audience of classical music and opera consists of older, better educated, and of higher social status people than average cultural consumers. It is also located in the largest cities, with Parisians having a clear edge. Explanatory power of these factors is even stronger when people are asked about their taste or distaste for serious contemporary music, with the three factors of high social status, high educational level and strong musical background working together in combination to explain a propensity for contemporary music attendance. In the same time, listening to new music inherently involves a high potential for dissatisfaction. Two types of ensembles and festivals perform and promote new music: the ‘fostering invention’ type and the ‘mixing new with established contemporary music’ type. Audience of the first type is best described as consisting of stakeholders. The ultimate hope of the second type institutions is to reach lay audience. Based on two surveys of the audience of the InterContemporain Ensemble, one of the most important European organisations in the distribution of modern and contemporary music, the paper shows that lay audience displays loyalty to this highly demanding musical consumption only if it is able to supply ascetic benevolence in order to factor in the high potential for dissatisfaction with works of uncertain and variable value

The labour market for jazz musicians in Paris and London: Formal regulation and informal norms

This article examines the normative expectations freelance jazz musicians have about the material conditions of live performance work, taking London and Paris as case studies. It shows how price norms constitute an important reference point for individual workers in navigating the labour market. However, only rarely do they take ‘stronger’ form as a collective demand. Two further arguments are made: first, that the strength of norms varies very widely across labour markets, being much stronger on jobs where other qualitative attractions (such as the scope for creative autonomy) are weak. Second, in the Paris case, an ostensibly solidaristic social insurance mechanism (the Intermittence du Spectacle system) had the seemingly paradoxical effect of further weakening social norms around working conditions. Workers’ individual efforts to meet the system’s eligibility criteria often disrupted the emergence of collective expectations around pricing, and in some cases the existence of formal regulation itself was stigmatized as stifling creativit