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Peng et al.
The import of acetyl-CoA into the ER lumen by AT-1/SLC33A1 is essential for the N-lysine acetylation of ER-resident and ER-transiting proteins. A point-mutation (S113R) in AT-1 has been associated with a familial form of spastic paraplegia. Here, we report that AT-1S113R is unable to form homodimers in the ER membrane and is devoid of acetyl-CoA transport activity. The reduced influx of acetyl-CoA into theERlumen results in reduced acetylation ofERproteins and an aberrant form of autophagy. Mice homozygous for the mutation display early developmental arrest. In contrast, heterozygous animals develop to full term, but display neurodegeneration and propensity to infections, inflammation, and cancer. The immune and cancer phenotypes are contingent on the presence of pathogens in the colony, whereas the nervous system phenotype is not. In conclusion, our results reveal a previously unknown aspect of acetyl-CoA metabolism that affects the immune and nervous systems and the risk for malignancies.

Osting et al.
Intraoperative magnetic resonance imaging (MRI) has been proposed as a method to optimize intracerebral targeting and for tracking infusate distribution in gene therapy trials for nervous system disorders. We thus investigated possible effects of two MRI contrast agents, gadoteridol (Gd) and galbumin (Gab), on the distribution and levels of transgene expression in the rat striatum and their effect on integrity and stability of recombinant adeno-associated virus (rAAV) particles. MRI studies showed that contrast agent distribution did not predict rAAV distribution. However, green fluorescent protein (GFP) immunoreactivity revealed an
increase in distribution of rAAV5-GFP, but not rAAV2-GFP, in the presence of Gd when compared with viral vector injected alone. In contrast, Gab increased the distribution of rAAV2-GFP not rAAV5-GFP. These observations pointed to a direct effect of infused contrast agent on the rAAV particles. Negative-stain electron microscopy (EM), DNAase treatment, and differential scanning calorimetry (DSC) were used to monitor rAAV2 and rAAV5 particle integrity and stability following contrast agent incubation. EMs of rAAV2-GFP and rAAV5-GFP particles pretreated with Gd appear morphologically similar to the untreated sample; however,
Gab treatment resulted in surface morphology changes and aggregation. A compromise of particle integrity was suggested by sensitivity of the packaged genome to DNAase treatment following Gab incubation but not Gd for both vectors. However, neither agent significantly affected particle stability when analyzed by DSC. An increase in Tm was observed for AAV2 in lactated Ringer’s buffer. These results thus highlight potential interactions between MRI contrast agents and AAV that might affect vector distribution and stability, as well as the stabilizing effect of lactated Ringer’s solution on AAV2.

Vivanco et al.
The purpose of this study was to compare computed tomography density (rCT) obtained using typical clinical computed tomography scan parameters to ash density (rash), for the prediction of densities of femoral head trabecular bone from hip fracture patients. An experimental study was conducted to investigate the relationships between rash and rCT and between each of these densities and rbulk and rdry . Seven human femoral heads from hip fracture patients were computed tomography–scanned ex vivo, and 76 cylindrical trabecular bone specimens were collected. Computed tomography density was computed from computed tomography images by using a calibration Hounsfield units–based equation, whereas rbulk , rdry and rash were determined experimentally. A large variation was found in the mean Hounsfield units of the bone cores (HUcore) with a constant bias from rCT to rash of 42.5 mg/cm3. Computed tomography and ash densities were linearly correlated (R2 = 0.55, p \ 0.001). It was demonstrated that rash provided a good estimate of rbulk (R2 =0.78, p \ 0.001) and is a strong predictor of rdry (R2 = 0.99, p \ 0.001). In addition, the rCT was linearly related to rbulk (R2 = 0.43, p \ 0.001) and rdry (R2 = 0.56, p \ 0.001). In conclusion, mineral density was an appropriate predictor of rbulk and rdry, and rCTwas not a surrogate for rash. There were linear relationships between rCT and physical densities; however, following the experimental protocols of this study to determine rCT, considerable scatter was present in the rCT relationships.