To understand the role of 14-3-3 in the differential regulation of tau isoforms, we have performed Studies on the interaction and aggregation of 3R-tau and 4R-tau, either phosphorylated or unphosphorylated, with 14-3-3 zeta. We show by Surface plasmon resonance studies that the interaction CYT11387 between Unphosphorylated 3R-tau and 14-3-3 zeta is similar to 3-folds higher than that between unphosphorylated 4R-tau and 14-3-3 zeta. Phosphorylation
of tau by Protein kinase A (PKA) increases the affinity of both 3R- and 4R-tau for 14-3-3 zeta to a similar level. An in vitro aggregation assay employing both transmission electron microscopy and fluorescence spectroscopy revealed the aggregation of unphosphorylated 4R-tau to be significantly higher than that of unphosphorylated 3R-tau following the induction of 14-3-3 zeta. The filaments formed from 3R- and 4R-tau were almost similar in morphology. In contrast, the aggregation of both 3R- and 4R-tau was reduced to a similar low level after phosphorylation with PKA. Taken together, these results suggest that 14-3-3 zeta exhibits a similar PFTα role for tau isoforms after PKA-phosphorylation,
but a differential role for unphosphorylated tau. The significant aggregation of 4R-tau by 14-3-3 zeta suggests that 14-3-3 may act as an inducer in the generation of 4R-tau-predominant neurofibrillary tangles in tauopathies. (C) 2009 Elsevier Inc. All rights reserved.”
“Since the first success in cloning sheep, the production
of viable animals by somatic cell nuclear transfer (SCNT) has developed significantly. Cattle are by far the most successfully cloned species but, despite this, the technique is still associated with a high incidence of pregnancy failure and accompanying placental and fetal pathologies. Pre- and early post-implantation losses can affect up to 70% of the pregnancies. In the surviving pregnancies, placentomegaly and fetal overgrowth are commonly observed, but the incidence varies widely, depending on the genotype of the nuclear donor cell and differences in SCNT procedures. In all cases, the placenta is central to the onset of the pathologies. Although cellular organisation of the SCNT placenta appears normal, placental vascularisation is modified and fetal-to-maternal tissue ratios are slightly PF-04929113 concentration increased in the SCNT placentomes. In terms of functionality, steroiclogenesis is perturbed and abnormal estrogen production and metabolism probably play an important part in the increased gestation length and lack of preparation for parturition observed in SCNT recipients. Maternal plasma concentrations of pregnancy-associated glycoproteins are increased, mostly due to a reduction in turnover rate rather than increased placental production. Placental glucose transport and fructose synthesis appear to be modified and hyperfructosemia has been observed in neonatal SCNT calves.