Regulation of C. elegans life-span by insulinlike signaling in the nervous system.

An insulinlike signaling pathway controls Caenorhabditis elegans aging, metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity.

Conjugating plasmids are preferred targets for Tn7.

Most transposons display target site selectivity, inserting preferentially into sites that contain particular features. The bacterial transposon Tn7 possesses the unusual ability to recognize two different classes of target sites. Tn7 inserts into these classes of target sites through two transposition pathways mediated by different combinations of the five Tn7-encoded transposition proteins. In one transposition pathway, Tn7 inserts into a unique site in the bacterial chromosome, attTn7, through specific recognition of sequences in attTn7; the other transposition pathway ignores the attTn7 target. Here we examine targets of the non-attTn7 pathway and find that Tn7 preferentially inserts into bacterial plasmids that can conjugate between cells. Furthermore, Tn7 appears to recognize preferred targets through the conjugation process, as we show that Tn7 inserts poorly into plasmids containing mutations that block plasmid transfer. We propose that Tn7 recognizes preferred targets through features of the conjugation process, a distinctive target specificity that offers Tn7 the ability to spread efficiently through bacterial populations.

Levels of p53 protein increase with maturation in human hematopoietic cells.

Transfection of the wild-type p53 gene into malignant cell lines usually results in an inhibition of proliferation. However, the physiological function of the endogenous p53 gene product has been difficult to ascertain. In order to examine whether p53 is involved in the regulation of proliferation and/or differentiation of hematopoietic tissue, we modified a recently developed flow cytometric assay to assess p53 protein expression in normal human hematopoietic cells, primary leukemias, and selected leukemia cell lines. In normal human bone marrow, p53 protein was not detected in the proliferative, progenitor cell populations identified by the cell surface antigens CD34 (progenitor cells of multiple lineages) or glycophorin (erythroid precursors). In contrast, low but detectable levels of p53 protein were observed in the nonproliferative, mature lymphoid, granulocytic, and monocytic cell populations. Similarly, p53 levels increased and DNA synthesis decreased during 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of ML-1 myeloblastic leukemia cells. Both of these results suggest that endogenous, wild-type p53 protein may play a role in hematopoietic cell maturation, possibly by contributing to the inhibition of proliferation that occurs during terminal differentiation. Leukemia cells deviated from this pattern of expression: (a) in contrast to the normal, proliferative bone marrow progenitor cells, a significant percentage of patient leukemia samples expressed detectable levels of p53 protein; and (b) leukemia cell lines exhibited lineage-specific abnormalities in p53 expression, with overexpression in lymphoid cell lines and lack of expression in myeloid cell lines.