1,721,052 research outputs found
Cyp26 genes a1, b1 and c1 are down-regulated in Tbx1 null mice and inhibition of Cyp26 enzyme function produces a phenocopy of DiGeorge Syndrome in the chick.
No full textES2, a gene deleted in DiGeorge syndrome, encodes a nuclear protein and is expressed during early mouse development, where it shares an expression domain with a Goosecoid-like gene
No full textSubmicroscopic deletions at 22q11.2: Variability of the clinical picture and delineation of a commonly deleted region
No full textLow-copy number repeat sequences flank the DiGeorge/Velocardiofacial syndrome loci at 22q11
No full textVelo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus
No full textThe Role of CHD7 in the Transcriptional Control of Heart Development
No full textChromatin remodelling provides a key mechanism for the regulation of gene expression through dynamic alterations in nucleosome occupancy at promoters and enhancers. Haploinsufficiency for the ATP-dependent chromatin remodeller chromodomain-helicase-DNA-binding protein 7 (CHD7) causes human CHARGE syndrome. CHARGE is characterised by a distinct pattern of congenital anomalies, including cardiovascular malformations, and has traditionally been considered a neurocristopathy. However, a number of the congenital heart defects associated with CHARGE cannot be attributed to disruption to the neural crest alone. This thesis therefore addresses the tissue-specific requirements and roles for CHD7 during cardiogenesis. CHD7 protein is shown to be present throughout the developing heart until E13.5. Conditional ablation of Chd7 in the early cardiogenic mesoderm results in embryonic lethality due to severe cardiovascular defects. These include haemorrhaging and oedema, major venous and arterial pole malformations, and disruption to cardiac innervation and vascularisation. To further dissect tissue-specific requirements for CHD7, cardiomyocyte-, second heart field- and endothelial-specific knockdowns were also performed. Each cross results in a milder subset of the cardiac defects observed after mesodermal ablation, indicating that CHD7 is required in multiple lineages within the cardiogenic mesoderm. Microarray analysis and validation by in situ hybridisation were used to identify genes dysregulated in the heart following mesodermal Chd7 ablation. These included components of the Semaphorin and Slit-Robo signalling pathways, which have known roles in heart development. Furthermore, aberrant expression of genes involved in calcium handling within cardiomyocytes is seen. Excitation-contraction coupling is disrupted in mutant embryonic cardiomyocytes, demonstrating relevance of the gene expression changes at the cellular level. This work reveals a requirement for CHD7 in mesodermal cardiac progenitors for both inflow and outflow tract development. Novel pathways are identified downstream of CHD7 activity in the developing heart, including the extracellular Semaphorin and Slit-Robo pathways, as well as components of the excitation-contraction coupling machinery
Mouse embryo phenotyping using high-resolution 3D imaging
No full textThe immense challenge of annotating the entire mouse genome has stimulated development of cutting-edge imaging technologies in a drive for novel information. These techniques promise to improve our understanding of the genes involved in embryo development, at least one third of which have been shown to be essential. Aligning advanced imaging technologies with biological needs will be fundamental to maximising the number of phenotypes discovered in the coming years. International efforts are underway to meet this challenge through an integrated and sophisticated approach to embryo phenotyping, which will include advanced imaging tools. This thesis investigates advanced imaging methodologies and computational image analysis techniques for mouse embryo phenotyping using magnetic resonance imaging (MRI). Additionally, the novel application of an emerging method called photoacoustic imaging is demonstrated for imaging mouse embryos in utero. First, the lack of tissue staining capabilities that currently limits embryo MR imaging was addressed by investigating the MRI staining properties of two readily available contrast agents and their underlying contrast enhancement mechanisms. A methodological framework was developed for high-throughput screening of embryos using diffusion MRI and implemented to study the splotch mouse model of human neural tube defects. A validation study was carried out to comprehensively assess the accuracy of volumetric measurements generated using a computational image analysis method called segmentation propagation. Finally, an all-optical photoacoustic scanner and novel time-reversal image reconstruction algorithm were developed, enabling photoacoustic imaging of whole embryos in utero. Overall, this thesis presents advanced imaging methodologies and computational image analysis techniques that may form an essential part of the toolkit available for annotating the mouse genome and facilitate identification of novel phenotypes in the coming years
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
- …
