Colocalization of 14-3-3 Proteins with SOD1 in Lewy Body-Like Hyaline Inclusions in Familial Amyotrophic Lateral Sclerosis Cases and the Animal Model

Background and Purpose: Cu/Zn superoxide dismutase (SOD1) is a major component of Lewy body-like hyaline inclusion (LBHI) found in the postmortem tissue of SOD1-linked familial amyotrophic lateral sclerosis (FALS) patients. In our recent studies, 14-3-3 proteins have been found in the ubiquitinated inclusions inside the anterior horn cells of spinal cords with sporadic amyotrophic lateral sclerosis (ALS). To further investigate the role of 14-3-3 proteins in ALS, we performed immunohistochemical analysis of 14-3-3 proteins and compared their distributions with those of SOD1 in FALS patients and SOD1-overexpressing mice. Methods: We examined the postmortem brains and the spinal cords of three FALS cases (A4V SOD1 mutant). Transgenic mice expressing the G93A mutant human SOD1 (mutant SOD1-Tg mice), transgenic mice expressing the wild-type human SOD1 (wild-type SOD1-Tg mice), and non-Tg wild-type mice were also subjected to the immunohistochemical analysis. Results: In all the FALS patients, LBHIs were observed in the cytoplasm of the anterior horn cells, and these inclusions were immunopositive intensely for pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$. In the mutant SOD1-Tg mice, a high degree of immunoreactivity for misfolded SOD1 (C4F6) was observed in the cytoplasm, with an even greater degree of immunoreactivity present in the cytoplasmic aggregates of the anterior horn cells in the lumbar spinal cord. Furthermore, we have found increased 14-3-3$\beta$ and 14-3-3$\gamma$ immunoreactivities in the mutant SOD1-Tg mice. Double immunofluorescent staining showed that C4F6 and 14-3-3 proteins were partially co-localized in the spinal cord with FALS and the mutant SOD1-Tg mice. In comparison, the wild-type SOD1-Tg and non-Tg wild-type mice showed no or faint immunoreactivity for C4F6 and 14-3-3 proteins (pan 14-3-3, 14-3-3$\beta$, and 14-3-3$\gamma$) in any neuronal compartments. Discussion: These results suggest that 14-3-3 proteins may be associated with the formation of SOD1-containing inclusions, in FALS patients and the mutant SOD1-Tg mice.Mathematic

Cerebellar alterations in the weaver mouse

The fine structure of the cerebellum of weaver mouse was examined and the paucity of granule cells and their axons, the parallel fibers, was confirmed. Unexpectedly, however, the dendritic spines of the Purkinje cells which, in normal animals, are the postsynaptic mates of the parallel fibers, were present. Furthermore, their essential morphology and their staining reactions were indistinguishable from those of the Purkinie cell dendritic spines in normal animals. Possible mechanisms of development are discussed

The Fine Structure of Cerebral Fluid Accumulation: III. Extracellular Spread of Cryptococcal Polysaccharides in the Acute Stage

Total quality management (TQM) for new product development (NPD) implies first, external quality (EQ): a focus on market demands and organizational embedding; second, internal quality (IQ): the efficiency of the primary NPD processes, and third, process quality (PQ): an orientation on development of NPD competencies. Good quality management in NPD concerning all three types of quality is only achieved when, in addition to the so-called system-technical approach, ample attention is paid to the social dynamics of NPD management. Social dynamics are a main element of dynamic NPD management, which further comprises configurational dynamics and the balancing of short- and long-term NPD performance (again in terms of EQ, IQ and PQ). Three clusters of social-dynamical aspects are worked out conceptually, operationalized and linked to performance: leadership, collective mind and narratives. Based on a multiple case study research, empirical findings will be presented concerning social-dynamical aspects in practice. In our conclusions we will also reflect upon the usefulness of these concepts for further theory development in the area of dynamic NPD management related to TQM