A Combination Theorem for Metric Bundles

We define metric bundles/metric graph bundles which provide a purely topological/coarse-geometric generalization of the notion of trees of metric spaces a la Bestvina-Feighn in the special case that the inclusions of the edge spaces into the vertex spaces are uniform coarsely surjective quasi-isometries. We prove the existence of quasi-isometric sections in this generality. Then we prove a combination theorem for metric (graph) bundles (including exact sequences of groups) that establishes sufficient conditions, particularly flaring, under which the metric bundles are hyperbolic. We use this to give examples of surface bundles over hyperbolic disks, whose universal cover is Gromov-hyperbolic. We also show that in typical situations, flaring is also a necessary condition.Comment: v3: Major revision: 56 pages 5 figures. Many details added. Characterization of convex cocompact subgroups of mapping class groups of surfaces with punctures in terms of relative hyperbolicity given v4: Final version incorporating referee comments: 63 pages 5 figures. To appear in Geom. Funct. Ana

Relative Hyperbolicity, Trees of Spaces and Cannon-Thurston Maps

We prove the existence of continuous boundary extensions (Cannon-Thurston maps) for the inclusion of a vertex space into a tree of (strongly) relatively hyperbolic spaces satisfying the qi-embedded condition. This implies the same result for inclusion of vertex (or edge) subgroups in finite graphs of (strongly) relatively hyperbolic groups. This generalises a result of Bowditch for punctured surfaces in 3 manifolds and a result of Mitra for trees of hyperbolic metric spaces.Comment: 27pgs No figs, v3: final version, incorporating referee's comments, to appear in Geometriae Dedicat

The Lockheed OSO-8 program. Analysis of data from the mapping X-ray heliometer experiment

The final report describes the extent of the analysis effort, and other activities associated with the preservation and documentation of the data set are described. The main scientific results, which are related to the behavior of individual solar activity regions in the energy band 1.5 - 15 keV, are summarized, and a complete bibliography of publications and presentations is given. Copies of key articles are also provided

Role of Winged Helix Transcription Factor (WIN) in the Regulation of Sertoli Cell Differentiated Functions: WIN Acts as an Early Event Gene for Follicle-Stimulating Hormone

Members of the winged helix transcription factor family are known to regulate epithelial cell differentiation by regulating cell-specific gene expression. rWIN is a newly discovered member of the winged helix family shown to be present in the adult rat testis. In the testis the human homolog of rWIN, HFH-11, was localized to the germ cells (i.e. spermatocytes and spermatids) undergoing spermatogenesis. In the present study we show that rWIN is also expressed in testicular Sertoli cells. Sertoli cells are the epithelial component of the semi-niferous tubule and provide both the cytoarchitectural support and the microenvironment for developing germ cells. The presence of rWIN in Sertoli cells was confirmed by Northern blot and RT-PCR analysis. The rWIN transcript size in the Sertoli cells was different from the germ cell transcript that is probably due to alternative splicing or modifications of the 3-untranslated region. At least two spliced variants of rWIN were observed in the Sertoli cells corresponding to the deletion of an exon in the DNA-binding region. Long term stimulation of cultured Sertoli cells with the gonadotropin FSH down-regulated rWIN expression. In contrast, short-term stimulation (2 h) transiently up-regulated rWIN expression. The FSH-induced transient stimulation of rWIN precedes expression of the transferrin gene that is a marker of Sertoli cell differentiation. FSH-induced transferrin promoter activity was inhibited when cultured Sertoli cells were treated with an antisense oligonucleotide to rWIN. Interestingly , the constitutive overexpression of the DNA-binding domain of rWIN also down-regulated transferrin promoter activity. Analysis of the transferrin promoter with various deletion mutations suggested that rWIN acts at an upstream gene of the transferrin promoter. The results indicate that a transient up-regulation of rWIN in part mediates the ability of FSH to activate the transferrin promoter, which can be inhibited with a rWIN antisense oligonucleotide or constitutive expression of the rWIN DNA-binding domain. The current study demonstrates that rWIN acts as an early event gene for FSH actions on Sertoli cells and that rWIN appears to have a role in the regulation of Sertoli cell differentiated functions. (Endocrinology 141: 2758 –2766, 2000

Patterns of DNA Methlyation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region (Melzner et al. 2002). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system, and anthropometric measures. In phase 1, our combined analyses of 313 individuals documented a distinct and consistent overall pattern of differential DNA methylation across seven CpG sites of LEP core promoter in all ethnicities and both sexes. This pattern replicates those identified in previous studies, suggesting a conserved core promoter region across populations. Phase 2 analyses of two of the four populations (n = 239), correlating methylation at the C/EBPα transcription binding site (TBS) with metabolic and anthropometric biomarkers reflecting LEP roles, showed that stature, which reflects bone growth and remodeling, was significantly and inversely correlated with the percentage of DNA methylation at this site in both sexes. We suggest that variation in DNA methylation along the LEP core promoter plays a substantial role in energy signals affecting both adipogenesis and bone metabolism

Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells

Neural crest stem cells (NCSCs) persist in peripheral nerves throughout late gestation but their function is unknown. Current models of nerve development only consider the generation of Schwann cells from neural crest, but the presence of NCSCs raises the possibility of multilineage differentiation. We performed Cre-recombinase fate mapping to determine which nerve cells are neural crest derived. Endoneurial fibroblasts, in addition to myelinating and non-myelinating Schwann cells, were neural crest derived, whereas perineurial cells, pericytes and endothelial cells were not. This identified endoneurial fibroblasts as a novel neural crest derivative, and demonstrated that trunk neural crest does give rise to fibroblasts in vivo, consistent with previous studies of trunk NCSCs in culture. The multilineage differentiation of NCSCs into glial and non-glial derivatives in the developing nerve appears to be regulated by neuregulin, notch ligands, and bone morphogenic proteins, as these factors are expressed in the developing nerve, and cause nerve NCSCs to generate Schwann cells and fibroblasts, but not neurons, in culture. Nerve development is thus more complex than was previously thought, involving NCSC self-renewal, lineage commitment and multilineage differentiation

Elevated atmospheric sulfur levels off the Peruvian coast

Elevated levels of non‐sea‐salt sulfate and SO2 in samples collected off the west coast of South America indicate that there is a major source of atmospheric sulfur in the region of southern Peru and northern Chile. During a 1983 cruise, observed concentrations of non‐sea‐salt sulfur, SO2, selenium, arsenic, and antimony were comparable to levels reported for moderately polluted urban air. In contrast, methanesulfonic acid levels were typical of coastal marine air. Clearly, the elevated atmospheric sulfur levels in this region cannot be ascribed to oceanic organosulfur emissions. The major inputs are tentatively attributed to the smelting of sulfide ores which is a major industry in this region. The transport of smelter derived aerosols to this region may have a number of consequences for the atmospheric and oceanic chemistry of the Peruvian upwelling area