Elevated Proteasome Capacity Extends Replicative Lifespan in Saccharomyces cerevisiae

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking. To determine the importance of proteasome function in yeast aging, we established a method to modulate UPS capacity by manipulating levels of the UPS–related transcription factor Rpn4. While cells lacking RPN4 exhibit a decreased non-adaptable proteasome pool, loss of UBR2, an ubiquitin ligase that regulates Rpn4 turnover, results in elevated Rpn4 levels, which upregulates UPS components. Increased UPS capacity significantly enhances replicative lifespan (RLS) and resistance to proteotoxic stress, while reduced UPS capacity has opposing consequences. Despite tight transcriptional co-regulation of the UPS and oxidative detoxification systems, the impact of proteasome capacity on lifespan is independent of the latter, since elimination of Yap1, a key regulator of the oxidative stress response, does not affect lifespan extension of cells with higher proteasome capacity. Moreover, since elevated proteasome capacity results in improved clearance of toxic huntingtin fragments in a yeast model for neurodegenerative diseases, we speculate that the observed lifespan extension originates from prolonged elimination of damaged proteins in old mother cells. Epistasis analyses indicate that proteasome-mediated modulation of lifespan is at least partially distinct from dietary restriction, Tor1, and Sir2. These findings demonstrate that UPS capacity determines yeast RLS by a mechanism that is distinct from known longevity pathways and raise the possibility that interventions to promote enhanced proteasome function will have beneficial effects on longevity and age-related disease in humans

Incremental grouping of image elements in vision

One important task for the visual system is to group image elements that belong to an object and to segregate them from other objects and the background. We here present an incremental grouping theory (IGT) that addresses the role of object-based attention in perceptual grouping at a psychological level and, at the same time, outlines the mechanisms for grouping at the neurophysiological level. The IGT proposes that there are two processes for perceptual grouping. The first process is base grouping and relies on neurons that are tuned to feature conjunctions. Base grouping is fast and occurs in parallel across the visual scene, but not all possible feature conjunctions can be coded as base groupings. If there are no neurons tuned to the relevant feature conjunctions, a second process called incremental grouping comes into play. Incremental grouping is a time-consuming and capacity-limited process that requires the gradual spread of enhanced neuronal activity across the representation of an object in the visual cortex. The spread of enhanced neuronal activity corresponds to the labeling of image elements with object-based attention

Two distinct modes of sensory processing observed in monkey primary visual cortex (V1)

Even salient sensory stimuli are sometimes not detected. What goes wrong in the brain in that case? Here, the authors show that a late (> 100 msec) component of the neural activity in the primary visual cortex of the monkey is selectively suppressed when stimuli are not seen. As there is evidence that this activity depends on feedback from extrastriate areas, these findings suggest a specific role for recurrent processing when stimuli are reaching a perceptual level. Further results show that this perceptual level is situated between purely sensory and decision or motor stages of processing

Balanced cortical microcircuitry for maintaining information in working memory

Persistent neural activity in the absence of a stimulus has been identified as a neural correlate of working memory, but how such activity is maintained by neocortical circuits remains unknown. Here we show that the inhibitory and excitatory microcircuitry of neocortical memory-storing regions is sufficient to implement a corrective feedback mechanism that enables persistent activity to be maintained stably for prolonged durations. When recurrent excitatory and inhibitory inputs to memory neurons are balanced in strength, but offset in time, drifts in activity trigger a corrective signal that counteracts memory decay. Circuits containing this mechanism temporally integrate their inputs, generate the irregular neural firing observed during persistent activity, and are robust against common perturbations that severely disrupt previous models of short-term memory storage. This work reveals a mechanism for the accumulation and storage of memories in neocortical circuits based upon principles of corrective negative feedback widely used in engineering applications

Finite element analysis of stress-related degrade during drying of Corymbia citriodora and Eucalyptus obliqua

With the use of experimental wood properties and input moisture content field data, a predictive 3D stress–strain finite element analysis (FEA) model was developed allowing to predict the development of stress-related end splitting and surface checking degrade during conventional and vacuum wood drying. Simulations were carried out for two Australian hardwood species, messmate (Eucalyptus obliqua) and spotted gum (Corymbia citriodora), as these species contrast, in terms of wood properties, drying rates and stress degrade susceptibility. The simulations were performed using a 1/8 symmetry model where the full board dimensions are 1900 mm long × 30 mm thick × 100 mm wide. Moisture content field data model simulations were utilised in a three-dimensional FEA model by extruding a 2D moisture content field computed in the T–L plane across the radial direction to create a 3D model. Material mechanical properties and shrinkage were calculated in relation to moisture content, over discrete time intervals, using a quasi-static solver. End split failure was investigated at the board end, and surface check failure at the board surface, using a Tsai–Wu failure criterion. Simulations showed that messmate was more susceptible to end splitting than spotted gum and that conventionally dried messmate was more susceptible to surface checking than vacuum-dried messmate. The same results were observed from drying trials. The locations of predicted surface check failure also matched drying trials and are compared