No abstract

Background: Miro is a mitochondrial protein involved in mitochondrial trafficking.Results: Mitochondrial damage drives rapid Miro ubiquitination in a manner dependent on Ser-65 in Parkin; however, Miro degradation is delayed.Conclusion: Ubiquitination of Miro, rather than its degradation, could act as a signal for mitochondrial arrest and clearance.Significance: Disruption of the mitochondrial transport machinery could be implicated in Parkinson disease.

SummaryValosin-containing protein (VCP) is a highly expressed member of the type II AAA+ ATPase family. VCP mutations are the cause of inclusion body myopathy, Paget’s disease of the bone, and frontotemporal dementia (IBMPFD) and they account for 1%–2% of familial amyotrophic lateral sclerosis (ALS). Using fibroblasts from patients carrying three independent pathogenic mutations in the VCP gene, we show that VCP deficiency causes profound mitochondrial uncoupling leading to decreased mitochondrial membrane potential and increased mitochondrial oxygen consumption. This mitochondrial uncoupling results in a significant reduction of cellular ATP production. Decreased ATP levels in VCP-deficient cells lower their energy capacity, making them more vulnerable to high energy-demanding processes such as ischemia. Our findings propose a mechanism by which pathogenic VCP mutations lead to cell death.

A total of 161 patients with lobar or segmental consolidation were examined by realtime ultrasound and Doppler ultrasound. Air bronchograms were detected in 141 patients, fluid bronchograms in 27 patients, and parapneumonic effusion in 74 patients. In 36 patients with necrotizing pneumonia, ultrasound detected microabscesses in 33 (91.7%) compared with the air-fluid levels detected by standard chest radiographs in 20 patients (55.6%; p less than 0.05). Of 31 patients with tumors causing obstructive pneumonitis, 29 (93.5%) had tumors detected by chest ultrasound, whereas only 11 patients (35.5%) had chest radiographs that suggested a tumor was causing the obstructive pneumonitis (p less than 0.05). Chest ultrasound was used to guide thoracentesis for parapneumonic effusion in 65 patients, with a 100% success rate. Twenty-six patients with necrotizing pneumonia underwent ultrasound-guided needle aspiration of microabscesses. The procedure was successful in 24 patients (92.3%), and 21 patients (80.8%) had microbiologic confirmation. Twenty patients with tumor-associated obstructive pneumonitis received needle aspiration biopsy under ultrasound guidance; 19 patients (95.0%) had the histology confirmed. Five patients with malignancy manifesting as pulmonary consolidation underwent a diagnostic ultrasound-guided needle aspiration biopsy. Five patients (3.8%) developed complications of minimal pneumothorax or mild hemoptysis in 132 episodes of needle aspiration. We conclude that ultrasonography is useful for the evaluation of pulmonary consolidation. It can also be used for needle aspiration guidance for etiologic diagnosis of patients with complicated pneumonia.