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Small animal imaging is of increasing relevance in biomedical research. Studies systematically assessing the diagnostic accuracy of contrast-enhanced in vivo micro-CT of orthotopic glioma xenografts in mice do not exist. NOD/SCID/γc mice (n = 27) underwent intracerebral implantation of 2.5 × 10 GFP-Luciferase-transduced U87MG cells. Mice underwent bioluminescence imaging (BLI) to detect tumor growth and afterwards repeated contrast-enhanced (300 µl Iomeprol i.v.) micro-CT imaging (80 kV, 75 µAs, 360° rotation, 1,000 projections, 33 s scan time, resolution 40 × 40 × 53 µm, 0.5 Gy/scan). Presence of tumors, tumor diameter and tumor volume in micro-CT were rated by two independent readers. Results were compared with histological analyses. Six mice with tumors confirmed by micro-CT received fractionated irradiation (3 × 5 Gy every other day) using the micro-CT (5 mm pencil beam geometry). Repeated micro-CT scans were tolerated well. Tumor engraftment rate was 74 % (n = 20). In micro-CT, mean tumor volume was 30 ± 33 mm, and the smallest detectable tumor measured 360 × 620 µm. The inter-rater agreement (n = 51 micro-CT scans) for the item tumor yes/no was excellent (Spearman-Rho = 0.862, p < 0.001). Sensitivity and specificity of micro-CT were 0.95 and 0.71, respectively (PPV = 0.91, NPV = 0.83). BLI on day 21 after tumor implantation had a sensitivity and specificity of 0.90 and 1.0, respectively (PPV = 1.0, NPV = 0.5). Maximum tumor diameter and volume in micro-CT and histology correlated excellently (tumor diameter: 0.929, p < 0.001; tumor volume: 0.969, p < 0.001, n = 17). Irradiated animals showed a large central tumor necrosis. Longitudinal contrast enhanced micro-CT imaging of brain tumor growth in live mice is feasible at high sensitivity levels and with excellent inter-rater agreement and allows visualization of radiation effects. [ABSTRACT FROM AUTHOR]

The ability to fix nitrogen is widely, but sporadically distributed among the Bacteria and Archaea suggesting either a vertically inherited, ancient function with widespread loss across genera or an adaptive feature transferred laterally between co-inhabitants of nitrogen-poor environments. As previous phylogenetic studies of nifH and nifD have not completely resolved the evolutionary history of nitrogenase, sixty nifD, nifK, and combined nifDK genes were analyzed using Bayesian, maximum likelihood, and parsimony algorithms to determine whether the individual and combined datasets could provide additional information. The results show congruence between the 16S and nifDK phylogenies at the phyla level and generally support vertical descent with loss. However, statistically significant differences between tree topographies suggest a complex evolutionary history with the underlying pattern of vertical descent obscured by recurring lateral transfer events and different patterns of evolution between the genes. Results support inheritance from the Last Common ancestor or an ancient lateral transfer of the nif genes between Bacteria and Archaea, ongoing gene transfer between cohabitants of similar biogeographic regions, acquisition of nitrogen-fixing capability via symbiosis islands, possible xenologous displacement of one gene in the operon, and possible retention of ancestral genes in heterocystous cyanobacteria. Analyses support the monophyly of the Cyanobacteria, αβγ-Proteobacteria, and Actinobacteria ( Frankia) and provide strong support for the placement of Frankia nif genes at the base of combined the Cyanobacteria/Proteobacteria clades. [ABSTRACT FROM AUTHOR]

Fanconi anemia (FA) is a rare chromosomal-instability disorder associated with a variety of developmental abnormalities, bone marrow failure and predisposition to leukemia and other cancers. We have identified a homozygous missense mutation in the RAD51C gene in a consanguineous family with multiple severe congenital abnormalities characteristic of FA. RAD51C is a member of the RAD51-like gene family involved in homologous recombination–mediated DNA repair. The mutation results in loss of RAD51 focus formation in response to DNA damage and in increased cellular sensitivity to the DNA interstrand cross-linking agent mitomycin C and the topoisomerase-1 inhibitor camptothecin. Thus, biallelic germline mutations in a RAD51 paralog are associated with an FA-like syndrome. [ABSTRACT FROM AUTHOR]

Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia–like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian cancer. These include two frameshift-causing insertions, two splice-site mutations and two nonfunctional missense mutations. The mutations were found exclusively within 480 pedigrees with the occurrence of both breast and ovarian tumors (BC/OC; 1.3%) and not in 620 pedigrees with breast cancer only or in 2,912 healthy German controls. These results provide the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog and support the 'common disease, rare allele' hypothesis. [ABSTRACT FROM AUTHOR]