PACAP application improves functional outcome of chronic retinal ischemic injury in rats – evidence from electroretinographic measurements

Retinoprotective effects of pituitary adenylate cyclase activating polypeptide (PACAP) are well-known and have been demonstrated in various pathological conditions, such as diabetic retinopathy, excitotoxic retinal injury, UV light-induced degeneration and ischemic retinal lesion. The neuronal degeneration observed in the different retinal layers under the above pathological conditions can be successfully decreased by PACAP, however, whether this morphological improvement is also reflected in functional amelioration remains unknown. Therefore, our purpose was to investigate the protective effect of PACAP on the rat retina after bilateral common carotid artery occlusion (BCCAO) with electroretinography (ERG) to parallel the functional data with the previous morphological and neurochemical observations. Control eyes received saline treatment while PACAP was injected into the vitreous space of the other eye immediately after the induction of ischemia. Retinal damage and protective effects of PACAP were quantified by the changes in the wave forms and amplitudes. On postoperative days 2 and 14 several parameters were assessed with special attention to the changes of b wave. The results confirm that the previously described morphological protection induced by PACAP treatment is reflected in functional improvement in ischemic retinal lesions

Heat shock partially dissociates the overlapping modules of the yeast protein-protein interaction network: a systems level model of adaptation

Network analysis became a powerful tool in recent years. Heat shock is a well-characterized model of cellular dynamics. S. cerevisiae is an appropriate model organism, since both its protein-protein interaction network (interactome) and stress response at the gene expression level have been well characterized. However, the analysis of the reorganization of the yeast interactome during stress has not been investigated yet. We calculated the changes of the interaction-weights of the yeast interactome from the changes of mRNA expression levels upon heat shock. The major finding of our study is that heat shock induced a significant decrease in both the overlaps and connections of yeast interactome modules. In agreement with this the weighted diameter of the yeast interactome had a 4.9-fold increase in heat shock. Several key proteins of the heat shock response became centers of heat shock-induced local communities, as well as bridges providing a residual connection of modules after heat shock. The observed changes resemble to a "stratus-cumulus" type transition of the interactome structure, since the unstressed yeast interactome had a globally connected organization, similar to that of stratus clouds, whereas the heat shocked interactome had a multifocal organization, similar to that of cumulus clouds. Our results showed that heat shock induces a partial disintegration of the global organization of the yeast interactome. This change may be rather general occurring in many types of stresses. Moreover, other complex systems, such as single proteins, social networks and ecosystems may also decrease their inter-modular links, thus develop more compact modules, and display a partial disintegration of their global structure in the initial phase of crisis. Thus, our work may provide a model of a general, system-level adaptation mechanism to environmental changes.Comment: 24 pages, 6 figures, 2 tables, 70 references + 22 pages 8 figures, 4 tables and 8 references in the enclosed Supplemen