Genetic link between renal birth defects and congenital heart disease

Structural birth defects in the kidney and urinary tract are observed in 0.5% of live births and are a major cause of end-stage renal disease, but their genetic aetiology is not well understood. Here we analyse 135 lines of mice identified in large-scale mouse mutagenesis screen and show that 29% of mutations causing congenital heart disease (CHD) also cause renal anomalies. The renal anomalies included duplex and multiplex kidneys, renal agenesis, hydronephrosis and cystic kidney disease. To assess the clinical relevance of these findings, we examined patients with CHD and observed a 30% co-occurrence of renal anomalies of a similar spectrum. Together, these findings demonstrate a common shared genetic aetiology for CHD and renal anomalies, indicating that CHD patients are at increased risk for complications from renal anomalies. This collection of mutant mouse models provides a resource for further studies to elucidate the developmental link between renal anomalies and CHD

Current and future Burden of Communicable Diseases in the European Union and EEA/EFTA countries (BCoDE). Methodology protocol

Mangen M-J, Gibbons C, Kretzschmar M, et al. Current and future Burden of Communicable Diseases in the European Union and EEA/EFTA countries (BCoDE). Methodology protocol. ECDC Technical Report. Stockholm: ECDC; 2011

Current and future Burden of Communicable Diseases in the European Union and EEA/EFTA countries (BCoDE). Methodology protocol

Mangen M-J, Gibbons C, Kretzschmar M, et al. Current and future Burden of Communicable Diseases in the European Union and EEA/EFTA countries (BCoDE). Methodology protocol. ECDC Technical Report. Stockholm: ECDC; 2011

Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

Ciliary motion defects cause defective mucociliary transport (MCT) in primary ciliary dyskinesia (PCD). Current diagnostic tests do not assess how MCT is affected by perturbation of ciliary motion. In this study, we sought to use micro-optical coherence tomography (μOCT) to delineate the mechanistic basis of cilia motion defects of PCD genes by functional categorization of cilia motion. Tracheae from three PCD mouse models were analyzed using μOCT to characterize ciliary motion and measure MCT. We developed multiple measures of ciliary activity, integrated these measures, and quantified dyskinesia by the angular range of the cilia effective stroke (ARC). Ccdc39-/- mice, with a known severe PCD mutation of ciliary axonemal organization, had absent motile ciliary regions, resulting in abrogated MCT. In contrast, Dnah5-/- mice, with a missense mutation of the outer dynein arms, had reduced ciliary beat frequency (CBF) but preserved motile area and ciliary stroke, maintaining some MCT. Wdr69-/- PCD mice exhibited normal motile area and CBF and partially delayed MCT due to abnormalities of ciliary ARC. Visualization of ciliary motion using μOCT provides quantitative assessment of ciliary motion and MCT. Comprehensive ciliary motion investigation in situ classifies ciliary motion defects and quantifies their contribution to delayed mucociliary clearance

Assessment of ciliary phenotype in primary ciliary dyskinesia by micro-optical coherence tomography

Ciliary motion defects cause defective mucociliary transport (MCT) in primary ciliary dyskinesia (PCD). Current diagnostic tests do not assess how MCT is affected by perturbation of ciliary motion. In this study, we sought to use micro-optical coherence tomography (μOCT) to delineate the mechanistic basis of cilia motion defects of PCD genes by functional categorization of cilia motion. Tracheae from three PCD mouse models were analyzed using μOCT to characterize ciliary motion and measure MCT. We developed multiple measures of ciliary activity, integrated these measures, and quantified dyskinesia by the angular range of the cilia effective stroke (ARC). Ccdc39(–/–) mice, with a known severe PCD mutation of ciliary axonemal organization, had absent motile ciliary regions, resulting in abrogated MCT. In contrast, Dnah5(–/–) mice, with a missense mutation of the outer dynein arms, had reduced ciliary beat frequency (CBF) but preserved motile area and ciliary stroke, maintaining some MCT. Wdr69(–/–) PCD mice exhibited normal motile area and CBF and partially delayed MCT due to abnormalities of ciliary ARC. Visualization of ciliary motion using μOCT provides quantitative assessment of ciliary motion and MCT. Comprehensive ciliary motion investigation in situ classifies ciliary motion defects and quantifies their contribution to delayed mucociliary clearance

Neuronal Control of Metabolism, Department Jens Brüning, Max Planck Institute for Metabolism Research, Managing Director: Jens Brüning, Max Planck Society

We report the deployment of spiral acquisition for high-resolution structural imaging at 7T. Long spiral readouts are rendered manageable by an expanded signal model including static off-resonance and B0 dynamics along with k-space trajectories and coil sensitivity maps. Image reconstruction is accomplished by inversion of the signal model using an extension of the iterative non-Cartesian SENSE algorithm. Spiral readouts up to 25 ms are shown to permit whole-brain 2D imaging at 0.5 mm in-plane resolution in less than a minute. A range of options is explored, including proton-density and T2* contrast, acceleration by parallel imaging, different readout orientations, and the extraction of phase images. Results are shown to exhibit competitive image quality along with high geometric consistency

Global genetic analysis in mice unveils central role for cilia in congenital heart disease.

Congenital heart disease (CHD) is the most prevalent birth defect, affecting nearly 1% of live births; the incidence of CHD is up to tenfold higher in human fetuses. A genetic contribution is strongly suggested by the association of CHD with chromosome abnormalities and high recurrence risk. Here we report findings from a recessive forward genetic screen in fetal mice, showing that cilia and cilia-transduced cell signalling have important roles in the pathogenesis of CHD. The cilium is an evolutionarily conserved organelle projecting from the cell surface with essential roles in diverse cellular processes. Using echocardiography, we ultrasound scanned 87,355 chemically mutagenized C57BL/6J fetal mice and recovered 218 CHD mouse models. Whole-exome sequencing identified 91 recessive CHD mutations in 61 genes. This included 34 cilia-related genes, 16 genes involved in cilia-transduced cell signalling, and 10 genes regulating vesicular trafficking, a pathway important for ciliogenesis and cell signalling. Surprisingly, many CHD genes encoded interacting proteins, suggesting that an interactome protein network may provide a larger genomic context for CHD pathogenesis. These findings provide novel insights into the potential Mendelian genetic contribution to CHD in the fetal population, a segment of the human population not well studied. We note that the pathways identified show overlap with CHD candidate genes recovered in CHD patients, suggesting that they may have relevance to the more complex genetics of CHD overall. These CHD mouse models and \u3e8,000 incidental mutations have been sperm archived, creating a rich public resource for human disease modelling. Nature 2015 May 28; 521(7553):520-4

Hyperon signatures in the PANDA experiment at FAIR

We present a detailed simulation study of the signatures from the sequential decays of the triple-strange pbar p -> Ω+Ω- -> K+ΛbarK- Λ -> K+pbarπ+K-pπ- process in the PANDA central tracking system with focus on hit patterns and precise time measurement. We present a systematic approach for studying physics channels at the detector level and develop input criteria for tracking algorithms and trigger lines. Finally, we study the beam momentum dependence on the reconstruction efficiency for the PANDA detector