tax and rex Sequences of bovine leukaemia virus from globally diverse isolates: rex amino acid sequence more variable than tax.

Bovine leukaemia virus (BLV) is an important agricultural problem with high costs to the dairy industry. Here, we examine the variation of the tax and rex genes of BLV. The tax and rex genes share 420 bases and have overlapping reading frames. The tax gene encodes a protein that functions as a transactivator of the BLV promoter, is required for viral replication, acts on cellular promoters, and is responsible for oncogenesis. The rex facilitates the export of viral mRNAs from the nucleus and regulates transcription. We have sequenced five new isolates of the tax/rex gene. We examined the five new and three previously published tax/rex DNA and predicted amino acid sequences of BLV isolates from cattle in representative regions worldwide. The highest variation among nucleic acid sequences for tax and rex was 7% and 5%, respectively; among predicted amino acid sequences for Tax and Rex, 9% and 11%, respectively. Significantly more nucleotide changes resulted in predicted amino acid changes in the rex gene than in the tax gene (P < or = 0.0006). This variability is higher than previously reported for any region of the viral genome. This research may also have implications for the development of Tax-based vaccines.

Studies of selected phenyltropanes at monoamine transporters.

3-Phenyltropane analogues of cocaine are useful neurobiologic tools for examining mechanisms of neurotransmitter transporters and psychostimulant drugs. They are also potential substitute medications for psychostimulant abuse. In this study, 18 3-phenyltropane analogues were characterized in uptake and binding studies at dopamine (DAT), norepinephrine (NET) and serotonin (SERT) transporters from the rat, and in binding at DAT in rat, rhesus monkey, and human brain tissue. In rat brain tissue, potency in inhibiting uptake generally correlated with the potency in inhibiting binding at all three transporters suggesting that none of these compounds have antagonist properties. At the DAT, there was a significant correlation of inhibitory potencies between the rat and monkey, the monkey and human, and the rat and human transporters although some compounds showed some species difference. These findings suggest that with regard to the 3-phenyltropane series, there is generally little pharmacologic difference between DATs from the three species examined, although binding data from rat may not be a perfect predictor of uptake inhibition in human.

Chronic lithium treatment decreases neuronal activity in the nucleus accumbens and cingulate cortex of the rat.

Although the efficacy of lithium as a mood stabilizer is well documented, the mechanism of its therapeutic effect associated with prolonged treatment remains unknown. Identifying discrete brain regions and neural pathways that are functionally altered following long-term lithium treatment is central to elucidating a psychotherapeutic mechanism. We have used a sensitive and quantitative histochemical assay for the determination of cytochrome oxidase (CO) activity, a mitochondrial marker of neuronal activity, to determine the effect of repeated lithium treatment on regional neuronal activity in the rat brain. Oral lithium treatment (21 days) selectively decreased cytochrome oxidase activity in the cingulate cortex and regions of the nucleus accumbens. These decreases were not seen after 5 days of lithium administration, although serum lithium concentrations were similar after both 5 and 21 days of treatment. The analysis of interregional correlations further suggests a role for amygdala pathways in the effects of lithium following 21 days of treatment. The implications of these data for understanding the mechanisms of action of lithium are discussed.

CART peptides in the central control of feeding and interactions with neuropeptide Y.

While CART peptides have been implicated as novel, putative peptide neurotransmitters/cotransmitters, behavioral effects of these peptides have not yet been demonstrated. In this study, we show the first behavioral effect of CART peptides. I.c.v. administration of CART peptide fragments inhibits feeding in rats. Moreover, injection of an antibody to CART peptide 82-103 stimulates feeding, suggesting that endogenous CART peptides exert an inhibitory tone on feeding. Injection of CART peptide 82-103 five min before NPY reduces the increase in feeding caused by injection of NPY alone. Also, in light microscopic immunohistochemical studies, NPY-positive varicosities were observed around CART peptide-positive cell bodies in the paraventricular nucleus of the hypothalamus. These data suggest functional interactions between CART peptides and NPY. These results indicate that CART peptides play a role in the control of food intake by the brain.