Rationale Mitochondria interact via actions of outer and inner membrane fusion proteins. The role of mitochondrial fusion on functioning of the heart, where mitochondria comprise ~30% of cardiomyocyte volume and their inter-myofilament spatial arrangement with other mitochondria is highly ordered, is unknown. Objective Model and analyze mitochondrial fusion defects in Drosophila melanogaster heart tubes with tincΔ4Gal4-directed expression of RNAi for Mitochondrial Assembly Regulatory Factor (MARF) and Optic atrophy 1 (Opa1). Methods and Results Live imaging analysis revealed that heart tube-specific knockdown of MARF or Opa1 increases mitochondrial morphometric heterogeneity and induces heart tube dilation with profound contractile impairment. Sarcoplasmic reticular structure was unaffected. Cardiomyocyte expression of human mitofusin (mfn) 1 or 2 rescued MARF RNAi cardiomyopathy, demonstrating functional homology between Drosophila MARF and human mitofusins. Suppressing mitochondrial fusion increased compensatory expression of nuclear-encoded mitochondrial genes, indicating mitochondrial biogenesis. The MARF RNAi cardiomyopathy was prevented by transgenic expression of superoxide dismutase 1. Conclusions Mitochondrial fusion is essential to cardiomyocyte mitochondrial function and regeneration. Reactive oxygen species are key mediators of cardiomyopathy in mitochondrial fusion-defective cardiomyocytes. Postulated mitochondrial-ER interactions mediated uniquely by mfn2 appear dispensable to functioning of the fly heart.

A variety of tumors, including primary malignant tumors, secondary malignant tumors, and benign tumors, can occur in the tracheobronchial tree. Primary malignant tumors commonly originate from the surface epithelium or the salivary glands, whereas most benign tumors arise from the mesenchymal tissue. At computed tomography (CT), primary malignant tumors manifest as a polypoid lesion, a focal sessile lesion, eccentric narrowing of the airway lumen, or circumferential wall thickening. At fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET), most squamous cell carcinomas show high uptake, whereas adenoid cystic carcinoma and mucoepidermoid carcinoma show variable uptake depending on the grade of differentiation. High-grade malignancies tend to show high and homogeneous uptake. Carcinoid tumors commonly show intense enhancement at contrast material-enhanced CT, which can be helpful in making the diagnosis, and usually have lower uptake at FDG PET than would be expected for a malignant tumor. Secondary malignant tumors occur as a result of either hematogenous metastasis or direct invasion by a malignancy from an adjacent structure. Their CT manifestations are similar to those of primary malignant tumors, with uptake at FDG PET depending primarily on the metabolic activity and degree of differentiation of the primary tumor. Among the benign tumors, hamartoma and lipoma can show characteristic CT findings such as "popcorn" calcification or internal fat. However, CT findings in most benign tumors are nonspecific. At FDG PET, benign tumors usually show little or no uptake and can be differentiated from malignant tumors. Knowledge of the characteristic CT and FDG PET findings of tracheobronchial tumors can aid in diagnosis and treatment planning.

The dual-energy computed tomographic (CT) technique allows the differentiation of materials with large atomic numbers such as iodine and xenon. The basic principle of dual-energy CT is material decomposition based on attenuation differences at different energy levels. By using dual-energy CT angiography for the evaluation of perfusion defects in cases of pulmonary embolism, and using xenon CT for the evaluation of ventilation defects, it may be possible to replace perfusion and ventilation scanning. An iodine map from dual-energy CT can demonstrate the distribution of pulmonary perfusion, whereas xenon ventilation CT can be used to generate a ventilation map. Furthermore, the virtual nonenhanced dual-energy CT technique can be used for the evaluation of pulmonary nodule characteristics without acquisition of true nonenhanced CT images. Knowledge of the applications of dual-energy CT and the typical images produced may lead to wider use of dual-energy CT for pulmonary applications and better interpretation of the results.

A substantial proportion of PSNs detected at screening CT were transient. Transient PSNs could be predicted with high accuracy by using the features of young patient age, detection of the PSN at follow-up, blood eosinophilia, lesion multiplicity, large solid portion, and ill-defined lesion border.

Sporadic heart failure is thought to have a genetic component, but the contributing genetic events are poorly defined. Here, we used ultra-high-throughput resequencing of pooled DNAs to identify SNPs in 4 biologically relevant cardiac signaling genes, and then examined the association between allelic variants and incidence of sporadic heart failure in 2 large Caucasian populations. Resequencing of DNA pools, each containing DNA from approximately 100 individuals, was rapid, accurate, and highly sensitive for identifying common and rare SNPs; it also had striking advantages in time and cost efficiencies over individual resequencing using conventional Sanger methods. In 2,606 individuals examined, we identified a total of 129 separate SNPs in the 4 cardiac signaling genes, including 23 nonsynonymous SNPs that we believe to be novel. Comparison of allele frequencies between 625 Caucasian nonaffected controls and 1,117 Caucasian individuals with systolic heart failure revealed 12 SNPs in the cardiovascular heat shock protein gene HSPB7 with greater proportional representation in the systolic heart failure group; all 12 SNPs were confirmed in an independent replication study. These SNPs were found to be in tight linkage disequilibrium, likely reflecting a single genetic event, but none altered amino acid sequence. These results establish the power and applicability of pooled resequencing for comparative SNP association analysis of target subgenomes in large populations and identify an association between multiple HSPB7 polymorphisms and heart failure.