ABSTRACT
Females of the squirrelfish family (Holocentridae) accumulate higher levels of hepatic zinc than any other studied animal. This accumulation is accompanied by high expression of the zinc-binding protein, metallothionein (MT), and is strongly correlated to the onset of sexual maturity. In an attempt to further characterize the timeframe of this accumulation, and to possibly discern any potential mediators, we examined the physiology and endocrinology of the yearly reproductive cycle of mature female squirrelfish. There are two separate reproductive events during the year in December-January and again in March-April, as evidenced by peaks in ovarian growth, VTG production, steroid levels, zinc accumulation and redistribution. Increased hepatic zinc seems to be preceded by a necessary increase in MT, but this was not clearly correlated to plasma 17beta-estradiol, testosterone, or progesterone levels. The plasma zinc protein vitellogenin (VTG) is one, but probably not the predominant, vehicle for the transport of hepatic zinc to the ovary.
Subject(s)
Fishes/physiology , Reproduction , Zinc/physiology , Animals , Blotting, Western , Female , Fishes/metabolism , Zinc/metabolismABSTRACT
BZLF1 plays a key role in the induction of Epstein-Barr virus (EBV) replication. On the basis of limited sequence homology and mutagenesis experiments, BZLF1 has been described as a member of the bZip family of transcription factors, but this prospect has not been rigorously tested to date. Here, we present biophysical analysis of the multimerization domain of BZLF1, from three natural variants of EBV, and demonstrate for the first time that the region between amino acids 196 and 227 is sufficient to direct folding as a coiled-coil dimer in vitro.
Subject(s)
DNA-Binding Proteins/chemistry , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/chemistry , Trans-Activators/chemistry , Viral Proteins , Amino Acid Sequence , B-Lymphocytes , Cell Line , DNA-Binding Proteins/genetics , Genetic Variation , Herpesvirus 4, Human/genetics , Humans , Molecular Sequence Data , Peptides/analysis , Peptides/chemical synthesis , Peptides/genetics , Spectrophotometry, Ultraviolet , Temperature , Trans-Activators/genetics , Tumor Cells, CulturedABSTRACT
Loss of heterozygosity (LOH) for chromosome 10 is the most frequent genetic abnormality observed in high-grade gliomas. We have used fluorescent microsatellite markers to examine a series of 83 patients, 34 with anaplastic astrocytoma (grade 3) and 49 with glioblastoma multiforme (grade 4), for LOH of chromosome 10. Genotype analysis revealed LOH for all informative chromosome 10 markers in 12 (35%) of patients with grade 3 and 29 (59%) grade 4 tumours respectively, while partial LOH was found in a further eight (24%) grade 3 and ten (20%) grade 4 tumours. Partial LOH, was confined to the long arm (10q) in six and the short arm (10p) in three cases, while alleles from both arms were lost in four cases. Five tumours (one grade 3 and four grade 4) showed heterogeneity with respect to loss at different loci. There was a correlation between any chromosome 10 loss and poorer performance status at presentation (chi2 P = 0.005) and with increasing age at diagnosis (Mann-Whitney U-test P = 0.034) but not with tumour grade (chi2 p= 0.051). A Cox multivariate model for survival duration identified age (proportional hazards (PH), P= 0.004), grade (PH, P= 0.012) and any loss of chromosome 10 (PH, P= 0.009) as the only independent prognostic variables. Specifically, LOH for chromosome 10 was able to identify a subgroup of patients with grade 3 tumours who had a significantly shorter survival time. We conclude that LOH for chromosome 10 is an independent, adverse prognostic variable in high-grade glioma.
