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.

Fluid and epithelial cells obtained from the breasts of non-pregnant, non-lactating women by nipple aspiration, can be used for early diagnosis of breast neoplasms. However, since nipple aspirate fluid (NAF) with cells is obtainable from less than half of women sampled, the question arises: Is this method capable of targeting the women most likely to develop breast cancer? We approached this question with a 25-year prospective study to determine if subjects yielding NAF with or without epithelial cells were more likely to develop breast cancer during the follow-up period than subjects from whom no NAF or epithelial cells were obtained. Logistic regression analysis was used to determine relative risk (RR) with 95% confidence intervals (CI). The follow-up cohort of 972 was representative of the eligible cohort of 1605 for factors related to breast cancer risk and nipple aspiration outcome, and representative of the general population for breast cancer risk. After a mean follow-up period of 25 years, women with epithelial cells in NAF were significantly more likely to develop breast cancer (RR=1.92; CI=1.22-3.01; p

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Bovine leukemia virus contains a pXBL region encoding the 3' parts of four regulatory proteins (Tax, Rex, G4, R3) in overlapping reading frames. Here we report the pXBL polymorphisms of 30 isolates from four countries. Rates of overall and synonymous substitutions were consistently lower, and nucleotide/amino acid composition bias and codon bias higher, in more-overlapped than in less-overlapped regions. Ratios of nonsynonymous/synonymous substitutions were lowest in the tax gene and its subregions. The 5' parts of the four genes showed selection patterns corresponding to their genomic context outside of the pXBL region. Longer G4 variants due to a natural stop codon mutation had additional triple overlap with reduced sequence variability. These data support the concept that a higher level of overlapping in coding regions correlates with greater evolutionary constraint. Tax, the most conserved among the four regulatory proteins, showed purifying selection consistent with its importance in the viral life cycle.

Bovine leukemia virus and human T-cell leukemia viruses I and II, members of the Deltaretrovirus group, have two regulatory genes, tax and rex, that are coded in overlapping reading frames. We found that sequence variations in the rex gene of each virus result in amino acid differences significantly more often than variations in the tax gene. For all three viruses the highest ratio of non-synonymous to synonymous changes was found in the rex gene. In the overlapping regions of tax and rex, the second codon position of Rex corresponds to the third codon position of Tax. Nucleotide C was present in all genes of the three viruses at the highest frequency and this bias was most pronounced in the rex gene. More specifically we found that the C bias and nucleotide variation is greatest at the second codon position of Rex and the third codon position of Tax in the area of tax/rex overlap. Changes in the second codon position of Rex always resulted in amino acid change whereas changes in the third codon position of Tax resulted in amino acid changes less than a third of the time. Analysis of the amino acid frequencies in both proteins shows that there is a disproportionately large percentage of the amino acids alanine, proline, serine and threonine (the four amino acids whose second codon position is C) in Rex. These findings led us to hypothesize that the Rex protein can withstand more amino acid changes than can the Tax protein suggesting that the Tax protein experiences higher evolutionary constraints and is the more conserved of the two proteins.