Loss of FAM111B protease mutated in hereditary fibrosing poikiloderma negatively regulates telomere length.

Hereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in the FAM111B gene that encodes a nuclear trypsin-like serine protease. HFP patients present with symptoms including skin abnormalities, tendon contractures, myopathy and lung fibrosis. We characterized the cellular roles of human FAM111B using U2OS and MCF7 cell lines and report here that the protease interacts with components of the nuclear pore complex. Loss of FAM111B expression resulted in abnormal nuclear shape and reduced telomeric DNA content suggesting that FAM111B protease is required for normal telomere length; we show that this function is independent of telomerase or recombination driven telomere extension. Even though FAM111B-deficient cells were proficient in DNA repair, they showed hallmarks of genomic instability such as increased levels of micronuclei and ultra-fine DNA bridges. When mutated as in HFP, FAM111B was more frequently localized to the nuclear envelope, suggesting that accumulation of the mutated protease at the nuclear periphery may drive the disease pathology.

Sonification of combined action observation and motor imagery: Effects on corticospinal excitability.

Action observation and motor imagery are valuable strategies for motor learning. Their simultaneous use (AOMI) increases neural activity, with related benefits for motor learning, compared to the two strategies alone. In this study, we explored how sonification influences AOMI. Twenty-five participants completed a practice block based on AOMI, motor imagery and physical execution of the same action. Participants were divided into two groups: An experimental group that practiced with sonification during AOMI (sAOMI), and a control group, which did not receive any extrinsic feedback. Corticospinal excitability at rest and during action observation and AOMI was assessed before and after practice, with and without sonification sound, to test the development of an audiomotor association. The practice block increased corticospinal excitability in all testing conditions, but sonification did not affect this. In addition, we found no differences in action observation and AOMI, irrespective of sonification. These results suggest that, at least for simple tasks, sonification of AOMI does not influence corticospinal excitability; In these conditions, sonification may have acted as a distractor. Future studies should further explore the relationship between task complexity, value of auditory information and action, to establish whether sAOMI is a valuable for motor learning.