Increased Zinc and Manganese in Parallel with Neurodegeneration,Synaptic Protein Changes and Activation of Akt/GSK3 Signaling in Ovine CLN6 Neuronal Ceroid Lipofuscinosis

Mutations in the CLN6 gene cause a variant late infantile form of neuronal ceroid lipofuscinosis (NCL; Batten disease). CLN6 loss leads to disease clinically characterized by vision impairment, motor and cognitive dysfunction, and seizures. Accumulating evidence suggests that alterations in metal homeostasis and cellular signaling pathways are implicated in several neurodegenerative and developmental disorders, yet little is known about their role in the NCLs. To explore the disease mechanisms of CLN6 NCL, metal concentrations and expression of proteins implicated in cellular signaling pathways were assessed in brain tissue from South Hampshire and Merino CLN6 sheep. Analyses revealed increased zinc and manganese concentrations in affected sheep brain in those regions where neuroinflammation and neurodegeneration first occur. Synaptic proteins, the metal-binding protein metallothionein, and the Akt/GSK3 and ERK/MAPK cellular signaling pathways were also altered. These results demonstrate that altered metal concentrations, synaptic protein changes, and aberrant modulation of cellular signaling pathways are characteristic features in the CLN6 ovine form of NCL.     

The isolation of nonsense mutations in cell division cycle genes of the yeast Saccharomyces cerevisiae

Summary Nonsense mutations have been isolated in cell division cycle genes in a strain of Saccharomyces cerevisiae that carries a temperature-sensitive amber suppressor. These mutants may be valuable in identifying the products of genes involved in the cycle and in determining the pattern of their synthesis during the cell cycle.     

Plasmodium gallinaceum: induction of male gametocyte exflagellation by phosphodiesterase inhibitors.

The phosphodiesterase inhibitors, Squibb 20009, caffeine, and 8-bromo-cyclic adenosine monophosphate (8-bromo-cAMP) are capable of stimulating gametogenesis, thus implicating cyclic nucleotides in the initiation of this process. Squibb 20009 and 8-bromo-cAMP stimulated gametogenesis at pH 8.0 but not at pH 7.4 whereas caffeine stimulated gametogenesis at pH 8.0 and 7.4.