Autophagy is a ubiquitous catabolic process that causes cellular bulk degradation of cytoplasmic components and is generally associated with positive effects on health and longevity. Inactivation of autophagy has been linked with detrimental effects on cells and organisms. The antagonistic pleiotropy theory postulates that some fitness-promoting genes during youth are harmful during aging. On this basis, we examined genes mediating post-reproductive longevity using an RNAi screen. From this screen, we identified 30 novel regulators of post-reproductive longevity, including Through downstream analysis of, we identified that the inactivation of genes governing the early stages of autophagy up until the stage of vesicle nucleation, such as , strongly extend both life span and health span. Furthermore, our data demonstrate that the improvements in health and longevity are mediated through the neurons, resulting in reduced neurodegeneration and sarcopenia. We propose that autophagy switches from advantageous to harmful in the context of an age-associated dysfunction.

How ubiquitylation of multiple substrates, including repair proteins and histones, is regulated during nucleotide excision repair (NER) has been unclear. Gracheva et al. show that the histone H2A-ubiquitin binding factor ZRF1 is essential in NER as it mediates remodeling of the novel ubiquitin E3 complex responsible for monoubiquitylation of histone H2A at DNA lesion sites.

No abstract

Stereotactic guided laser-induced interstitial thermotherapy (SLITT) represents a minimal invasive method to produce necrosis in cerebral tumor tissue by local heating. The dose/response relationship relies on experimental studies and few clinical data performed in high field MR systems. A better understanding of the energy-dose/tissue response in human brain tumors is important to optimize this treatment modality. Twenty-four patients with gliomas were treated with SLITT, with a total of 30 laser procedures performed. Under local anesthesia 600 microns laser-fibers were inserted by stereotactic-guided technique into the center of the tumor. In a low field open MR system (0.2 T) the denaturation of the tumor using a neodymium YAG laser (1064 nm) was monitored by 3D-turbo FLASH T1-weighted sequences. Laser energy was applied in steps of 400 to 1200 Joules. Development of necrosis at a mean total energy dose of 2979 Joules could be monitored in all procedures. Two different thermal lesion architectures were observed. First signal changes were monitored after a mean of 1108 Joules and 1393 Joules, respectively. Mean max. total lesion size was 21.2 mm. The higher the total energy the larger was the thermolesion, but no linear relationship could be seen. Tumor tissue response showed no dependency on tumor grading. Monitoring of stereotactic guided laser-induced thermolesions in the low-power MR OPEN is feasible and safe. Although lesion size basically is energy dependent, it should be applied individually, since the thermal response in brain tumors varies due to different optical properties, even in the same tumor gradings.