Knowledge-based inferences across the hemispheres: domain makes a difference.

Language comprehension occurs when the left-hemisphere (LH) and the right-hemisphere (RH) share information derived from discourse [Beeman, M. J., Bowden, E. M., & Gernsbacher, M. A. (2000). Right and left hemisphere cooperation for drawing predictive and coherence inferences during normal story comprehension. Brain and Language, 71, 310-336]. This study investigates the role of knowledge domain across hemispheres, hypothesizing that the RH demonstrates inference processes for planning knowledge while the LH demonstrates inference processes for knowledge of physical cause and effect. In experiment 1, sixty-eight participants completed divided-visual-field reading tasks with 2-sentence stimuli that relied on these knowledge areas. Results showed that readers made more planning inferences from the RH and more physical inferences from the LH, indicating inference processes occur from each hemisphere dependent upon the knowledge domain required to support it. In experiment 2, sixty-four participants completed the same reading task with longer, story-length stimuli to demonstrate the effect in a more realistic setting. Experiment 2 results replicated the findings from experiment 1, extending previous findings, specifying that hemispheric differences for inferences rely on knowledge domains.

Proteasome inhibitors shorten replicative life span and induce a senescent-like phenotype of human fibroblasts.

The proteasome constitutes the main non-lysosomal cellular protease activity, and plays a crucial role not only in the disposal of unwanted material, but also in the regulation of numerous cellular processes. Previously, we have reported that during the replicative senescence of WI-38 fibroblasts there is a significant impairment in proteasome activity, which probably has important implications in the control of MAPK signaling and cellular proliferation. In this study, we report the potential role of the proteasome in the generation of the senescent phenotype in WI-38 fibroblasts. Our results indicate that inhibition of proteasome activity leads to an impairment in cell proliferation, and a shortening of the life span. The results also indicate that inhibition of the proteasome in young cells induces a premature senescent-like phenotype, as indicated by the increase in senescence-associated beta-galactosidase (SA beta-gal) activity and the abundance of both p21 and collagenase mRNAs, as well as a decreased level of EPC-1 mRNA known markers of cellular senescence, not previously shown to depend on proteasome activity. Together, our results suggest a molecular mechanism for the lack of responsiveness of human cells to growth factors, and point towards a role for the proteasome in the control of the life span of both cells and organisms.