Taken together, our in vitro study showed that BACE2 is degraded through the macrophagy–lysosome pathway and that lysosomal inhibition affects BACE2 processing of APP. Modulation of BACE2 degradation via the lysosomal pathway could be a new target for AD drug development. “
“Our eyes are always in motion. Even during periods of relative fixation we produce so-called ‘fixational eye movements’, which include microsaccades, drift and tremor. Mental fatigue can modulate saccade dynamics, but its effects on microsaccades and drift are unknown. Here we asked human subjects to perform a prolonged and demanding visual search task (a simplified

air traffic control task), with two difficulty levels, under both free-viewing and fixation conditions. Saccadic and microsaccadic velocity decreased with time-on-task whereas drift velocity check details increased, suggesting that ocular instability increases with mental fatigue. Task difficulty did not influence eye movements despite affecting reaction times, performance errors and subjective

complexity ratings. We propose that variations in eye movement dynamics with time-on-task are consistent with the activation of the brain’s sleep centers in correlation with mental fatigue. Covariation of saccadic and microsaccadic parameters moreover supports the hypothesis of a common generator for microsaccades find more and saccades. We conclude that changes in fixational and saccadic dynamics can indicate mental fatigue due to time-on-task, irrespective of task complexity. These findings suggest that fixational eye movement dynamics have the potential to Selleckchem Verteporfin signal the nervous system’s activation state. Our eyes are always in motion.

Even during the periods between saccades, smooth pursuit and reflexive eye movements we produce so called ‘fixational eye movements’, which include microsaccades, drift and tremor (Martinez-Conde et al., 2004). The superior colliculus is critical to triggering microsaccades and saccades (Rolfs et al., 2008; Hafed et al., 2009; Martinez-Conde et al., 2009, 2013; Otero-Millan et al., 2011) and for the control of selective attention, even without eye movements (Lovejoy & Krauzlis, 2010). Accordingly, studies have reported an influence of attention on saccades and microsaccades (Hafed & Clark, 2002; Engbert & Kliegl, 2003). Few studies, however, have addressed the potential effects of mental fatigue, i.e. the mental tiredness generated by time-on-task (TOT) and task complexity (TC), on microsaccade production (Hafed, 2003; Chen et al., 2008; Otero-Millan et al., 2008; Pastukhov & Braun, 2010; Benedetto et al., 2011). Indeed, only three studies to date have manipulated TC parametrically and measured the effects on microsaccade rate, with varied results (Chen et al., 2008; Pastukhov & Braun, 2010; Benedetto et al., 2011). A solitary preliminary report has addressed the effects of TOT on microsaccade rate (Hafed, 2003). No study has investigated how TOT and/or TC affect microsaccade velocity, or any drift parameters.