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Mantle upwelling is essential to the generation of new oceanic crust at mid-ocean ridges, and it is generally assumed that such upwelling is symmetric beneath active ridges. Here, however, we use seismic imaging to show that the isotropic and anisotropic structure of the mantle is rotated beneath the East Pacific Rise. The isotropic structure defines the pattern of magma delivery from the mantle to the crust. We find that the segmentation of the rise crest between transform faults correlates well with the distribution of mantle melt. The azimuth of seismic anisotropy constrains the direction of mantle flow, which is rotated nearly 10 degrees anticlockwise from the plate-spreading direction. The mismatch between the locus of mantle melt delivery and the morphologic ridge axis results in systematic differences between areas of on-axis and off-axis melt supply. We conclude that the skew of asthenospheric upwelling and transport governs segmentation of the East Pacific Rise and variations in the intensity of ridge crest processes.

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Tomographic images of upper mantle velocity structure beneath an overlapping spreading center (OSC) on the East Pacific Rise indicate that this ridge axis discontinuity is underlain by a continuous region of low P-wave velocities. The anomalous structure can be explained by an approximately 16-kilometer-wide region of high temperatures and melt fractions of a few percent by volume. Our results show that OSCs are not necessarily associated with a discontinuity in melt supply and that both OSC limbs are supplied with melt from a mantle source located beneath the OSC. We conclude that tectonic segmentation of the ridge by OSCs is not the direct result of magmatic segmentation at mantle depths.

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Seismic reflection data from the East Pacific Rise between 17 degrees 05' and 17 degrees 35'S image a magma lens that varies regularly in depth and width as ridge morphology changes, confirming the notion that axial morphology can be used to infer ridge magmatic state. However, at 17 degrees 26'S, where the ridge is locally shallow and broad, the magma lens is markedly shallower and wider than predicted from regional trends. In this area, submersible dives reveal recent volcanic eruptions. These observations indicate that it is where the width and depth of the magma chamber differ from regional trends, indicating an enhanced magmatic budget, that is diagnostic of current magmatism.

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Myeloid leukemias have been shown to secrete as well as respond to cytokines such as interleukin-3 (IL-3) with an increased growth rate and may therefore become self-stimulatory through an external autocrine mechanism. In vitro evidence that IL-3 is functional within the intracellular compartment has been obtained through modification of the murine IL-3 gene to encode for the amino acids SEKDEL on the carboxyl terminus of the protein, resulting in preferential intracellular retention. The ability of bone marrow-derived hematopoietic progenitor cells to increase their proliferative capacity through intracellular mechanisms was investigated in vivo using retroviruses containing the wild-type or SEKDEL-modified IL-3 gene, transcriptionally regulated by the retroviral long terminal repeat (LTR) or by the SV40 early promoter, in lethally irradiated, bone marrow-reconstituted mice. Bone marrow cells exposed to the N2KDEL virus containing the SEKDEL-modified IL-3 gene were shown by bioassay to retain large amounts of IL-3 intracellularly, and the presence of an integrated provirus containing the SEKDEL sequences was demonstrated by polymerase chain reaction (PCR) in the spleen and bone marrow of these animals. Transduction with all four types of IL-3 viruses resulted in dramatic increases in the circulating white blood cell (WBC) count; this myeloproliferative state occurred within several weeks following bone marrow transplantation (BMT), when viruses expressing the IL-3 or modified gene were under transcriptional regulation of the viral LTR, and approximately 2 months post-BMT, when they were under control of the SV40 internal promoter. Serum levels of IL-3 were measured in transplanted animals and found to be markedly increased in each case in which WBC elevation was observed, including mice receiving marrow transduced with constructs containing the IL-3 gene modified for intracellular retention. No animals were observed in which myeloproliferation occurred without secretion. From these experiments, it seems unlikely that exclusively intracellular mechanisms are a major contributor to the development of the myeloproliferative syndrome observed in these animals.

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Seismic data from the ultrafast-spreading (150 to 162 millimeters per year) southern East Pacific Rise show that the rise axis is underlain by a thin (less than 200 meters thick) extrusive volcanic layer (seismic layer 2A) that thickens rapidly off axis. Also beneath the rise axis is a narrow (less than 1 kilometer wide) melt sill that is in some places less than 1000 meters below the sea floor. The small dimensions of this molten body indicate that magma chamber size does not depend strongly on spreading rate as predicted by many ridge-crest thermal models. However, the shallow depth of this body is consistent with an inverse correlation between magma chamber depth and spreading rate. These observations indicate that the paradigm of ridge crest magma chambers as small, sill-like, midcrustal bodies is applicable to a wide range of intermediate- and fast-spreading ridges.

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N-cadherin is a calcium-dependent, cell adhesion molecule that has been proposed to play a role in morphogenesis in vertebrate embryos. Throughout early neural development, N-cadherin is expressed during the morphogenetic changes that occur when ectoderm, in response to neural induction, forms a neural plate and tube. To study the role of N-cadherin in these processes, cDNA clones encoding Xenopus laevis N-cadherin were isolated and used to study the expression of N-cadherin in frog embryos. These studies showed that N-cadherin RNA is not expressed at detectable levels in early cleavage embryos or in isolated ectoderm in the absence of neural induction. However, N-cadherin RNA rapidly appeared in ectoderm exposed to a heterologous neural inducer, indicating that N-cadherin expression, as an early response to induction, precedes the morphogenetic events associated with early neural development. The role of N-cadherin in these morphogenetic events was studied by ectopically expressing N-cadherin in the ectoderm of embryos prior to induction. The ectopic expression of this protein in ectoderm led to the formation of cell boundaries and to severe morphological defects. These results are consistent with the hypothesis that the morphogenetic changes associated with early neural development are controlled, in part, by the induced expression of N-cadherin in the neural plate.

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Products of ras genes are synthesized as precursors in the cytosol and transported to the plasma membrane by a process which involves posttraslational modification by fatty acid. In this paper, we present evidence for the occurrence in the cytosol of an intermediate modification of ras proteins prior to the fatty acid acylation. The modification is detected by a slight shift in the mobility of the protein on SDS polyacrylamide gel. The fatty acid acylation does not contribute to this mobility shift. This modification is affected by the dprl mutation which has recently been shown to affect the processing of yeast RAS proteins. To further characterize the nature of the modification event, we have cloned DPR1 gene from the DNA of Saccharomyces cerevisiae. The gene is actively transcribed in yeast cells producing mRNA of approximately 1.6 kb. Genes related to the DRP1 appear to be present in a distantly related yeast, Schizosaccharomyces pombe as well as in guinea pig and human cells.

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T cells and monocytes/macrophages (Mo) have been shown to play important roles in modulating the growth and differentiation of human erythroid and myeloid progenitors and have been implicated in the mechanisms of gamma interferon (gamma-IFN) mediated suppression of normal human marrow erythroid progenitors in vitro. In order to assess the importance of T cells and Mo in the growth of human megakaryocytic progenitors (CFU-Mk) in vitro and to investigate gamma-IFN effect on human megakaryocytopoiesis, normal human marrow (BM) was cultured in plasma clot in the presence and absence T cells, Mo and gamma-IFN under conditions that support the formation of CFU-Mk derived colonies. The removal of T cells from BM (BM-T) caused a significant decrease (71.3 +/- 3.2 colonies observed vs 231.2 +/- 38.5 colonies predicted) in both the number and size of CFU-Mk derived colonies, and no such changes were seen with Mo depletion (BM-Mo); co-culture of autologous T cells with BM depleted of both Mo and T cells (BM-Mo-T) caused a significant increase in CFU-Mk derived colonies and restored colony size. The addition of gamma-IFN (less than 50-10,000 IU/ml) to BM caused a dose dependent inhibition of CFU-Mk (0-90%) as evidenced by decreased colony numbers and reduced colony size. The addition of gamma-IFN (50-10,000 IU/ml) to BM-T caused reduced inhibition of CFU-Mk (0-60%); co-culture of T cells (but not Mo) pre-incubated with gamma-IFN (10,000 IU/ml; 1 hour, 37 C followed by washing X 3) resulted in supression of CFU-Mk (80% inhibition with the addition of 1:4 T cells:marrow cells). The results demonstrate that T cells have the ability to modulate the growth of human CFU-Mk in vitro and may, under appropriate conditions, either promote (normal T cells) or inhibit (gamma-IFN activated T Cells) human megakaryocytopoiesis.

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Hyla chrysoscelis (2n = 24) and H. versicolor (2n = 48) are a diploid-tetraploid species pair of tree frogs. Hybridization saturation of isolated 125I-labeled ribosomal RNAs (rRNAs) with filter-immobilized DNA shows that there are twice as many rRNA genes in the tetraploid as in the diploid. For the diploid, saturation occurs at 0.037%, from which it is calculated that there are about 618 copies of the (18 S + 28 S) rRNA genes per haploid genome. Analysis of the extent of hybridization and also the thermal stability of homologous and heterologous hybrids shows that considerably more base substitutions have occurred in the tetraploid rDNA genes than in the diploid since their divergence. This is interpreted to reflect either a relaxation of the gene regulatory "correction" mechanism hypothesized to be responsible for the maintenance of identical tandem rRNA genes in the tetraploid or a release of one gene set from the normal selective constraints.

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Previous in vitro studies on committed hematopoietic progenitors have suggested that polycythemia vera (PV) is a clonal disorder arising in a pluripotential hematopoietic stem cell. In this study, recently developed technics for clonal assay of a human multipotential progenitor cell (CFU-GEMM) were used to assess the functional characteristics of CFU-GEMM in 19 PV patients. These studies showed: (a) increased numbers of detectable CFU-GEMM in blood and bone marrow samples of PV patients as compared with normals (P less than 0.002 and P less than 0.02, respectively); (b) erythropoietic differentiation of PV CFU-GEMM without exogenous erythropoietin (Ep) in culture (in marked contrast to CFU-GEMM of both normals and subjects with secondary erythrocytosis which require exogenous Ep for terminal hemoglobinization of their erythroid component), a property shown by experiments with an anti-Ep antiserum to be related to increased sensitivity of PV CFU-GEMM to Ep; (c) increased megakaryocyte formation by PV CFU-GEMM as compared with normals (P less than 0.025); and (d) a linear relationship, extrapolating to the origin, between CFU-GEMM detected and cells cultured. These studies demonstrate that at least two clinical features of PV, increased erythropoiesis and megakaryocytopoiesis, are reflected in corresponding functional characteristics of PV CFU-GEMM, and provide direct evidence of distinctive pluripotential stem cell activity in this disorder.

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The distribution of labeled cells in the chaffinch brain has been examined by autoradiography after an intramuscular injection of [3H]testosterone. In the telencephalon labeled cells were particularly concentrated in nucleus magnocellularis neostriatalis anterioris, nucleus septalis lateralis, and hyperstriatum ventrale, pars caudale. In the diencephalon the nucleus periventricularis magnocellularis, the nucleus magnocellularis posterioris and the area infundibularis contained many heavily labeled cells. In the mesencephalon and medulla, labeled cells were found in the nucleus intercollicularis and in the nucleus nervi hypoglossi, respectively. Measurements of the density of grains per cell revealed (1) clear quantitative differences in the extent of labeling in different regions of the brain and (2) a wide variation in the density of labeling of individual cells within a region. The relationship between these sites of hormone binding and known sites of androgen action in the avian brain is discussed.

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