Snail promotes the cell-autonomous generation of Flk1 + endothelial cells through the repression of the microRNA-200 family

Expression of the transcription factor Snail is required for normal vasculogenesis in the developing mouse embryo. In addition, tumors expressing Snail have been associated with a more malignant phenotype, with both increased invasive properties and angiogenesis. Although the relationship between Snail and vasculogenesis has been noted, no mechanistic analysis has been elucidated. Here, we show that in addition to inducing an epithelial mesenchymal transition, Snail promotes the cell-autonomous induction of Flk1(+) endothelial cells in an early subset of differentiating mouse embryonic stem (ES) cells. Cells that become Flk1+ in response to Snail have a transcriptional profile specific to Gata6+primitive endoderm, but not the early Nanog+epiblast. We further show that Snail's ability to promote Flk1(+) endothelium depends on fibroblast growth factor signaling as well as the repression of the microRNA-200 (miR-200) family, which directly targets the 3′ UTRs of Flk1 and Ets1. Together, our results show that Snail is capable of inducing Flk1+ lineage commitment in a subset of differentiating ES cells through the down-regulation of the miR-200 family. We hypothesize that this mechanism of Snail-induced vasculogenesis may be conserved in both the early developing embryo and malignant cancers

Highly Ionized High Velocity Clouds: Intergalactic Gas in the Local Group or Distant Gas in the Galactic Halo?

We have recently identified several high velocity (V < -100 km/s) clouds in the directions of Mrk 509 and PKS 2155-304 that have unusual ionization properties. The clouds exhibit strong C IV absorption with little or no detectable low ion (C II, Si II) absorption or H I 21cm emission. As the closest known analog to the outer diffuse halos of damped Ly-alpha absorbers and the low H I column density metal line absorption systems seen in the spectra of high redshift quasars, these "C IV-HVCs" present unique opportunities for relating the conditions within the Milky Way halo and nearby intergalactic gas to the properties of galactic halos at higher redshift. The C IV-HVCs have ionization properties consistent with photoionization by extragalactic background radiation, though some contribution by collisional ionization within a hot plasma cannot be ruled out. The clouds are probably low density [n(H) ~ 10^-4 cm^-3], large [greater than several kiloparsecs], and mostly ionized [n(HI)/n(H) ~ 10^-3] regions located well beyond the neutral gas layer of the Galaxy. The presence of weak H I-HVCs detected through 21cm emission near both sight lines indicates that the C IV-HVCs trace the extended, ionized, low density regions of the H I-HVCs. Several lines of evidence, including very low thermal pressures (P/k ~ 2 cm^-3 K), favor a location for the C IV-HVCs in the Local Group or very distant Galactic halo.Comment: AASTEX manuscript and tables, 55 pages, 8 postscript figures. Astrophysical Journal, in pres

Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here, we describ

A crucial role for HVEM and BTLA in preventing intestinal inflammation

The interaction between the tumor necrosis factor (TNF) family member LIGHT and the TNF family receptor herpes virus entry mediator (HVEM) co-stimulates T cells and promotes inflammation. However, HVEM also triggers inhibitory signals by acting as a ligand that binds to B and T lymphocyte attenuator (BTLA), an immunoglobulin super family member. The contribution of HVEM interacting with these two binding partners in inflammatory processes remains unknown. In this study, we investigated the role of HVEM in the development of colitis induced by the transfer of CD4(+)CD45RB(high) T cells into recombination activating gene (Rag)(-/-) mice. Although the absence of HVEM on the donor T cells led to a slight decrease in pathogenesis, surprisingly, the absence of HVEM in the Rag(-/-) recipients led to the opposite effect, a dramatic acceleration of intestinal inflammation. Furthermore, the critical role of HVEM in preventing colitis acceleration mainly involved HVEM expression by radioresistant cells in the Rag(-/-) recipients interacting with BTLA. Our experiments emphasize the antiinflammatory role of HVEM and the importance of HVEM expression by innate immune cells in preventing runaway inflammation in the intestine

Apportionment of primary and secondary organic aerosols in Southern California during the 2005 Study of Organic Aerosols in Riverside (SOAR-1)

Ambient sampling was conducted in Riverside, California during the 2005 Study of Organic Aerosols in Riverside to characterize the composition and sources of organic aerosol using a variety of state-of-the-art instrumentation and source apportionment techniques. The secondary organic aerosol (SOA) mass is estimated by elemental carbon and carbon monoxide tracer methods, water soluble organic carbon content, chemical mass balance of organic molecular markers, and positive matrix factorization of high-resolution aerosol mass spectrometer data. Estimates obtained from each of these methods indicate that the organic fraction in ambient aerosol is overwhelmingly secondary in nature during a period of several weeks with moderate ozone concentrations and that SOA is the single largest component of PM1 aerosol in Riverside. Average SOA/OA contributions of 70−90% were observed during midday periods, whereas minimum SOA contributions of ~45% were observed during peak morning traffic periods. These results are contrary to previous estimates of SOA throughout the Los Angeles Basin which reported that, other than during severe photochemical smog episodes, SOA was lower than primary OA. Possible reasons for these differences are discussed

Spectroscopy and Time Variability of Absorption Lines in the Direction of the Vela Supernova Remnant

We present high resolution (R~75,000), high signal-to-noise (S/N~100) Ca II $\lambda$3933.663 and Na I $\lambda\lambda$5889.951, 5895.924 spectra of 68 stars in the direction of the Vela supernova remnant. The spectra comprise the most complete high resolution, high S/N, optical survey of early type stars in this region of the sky. A subset of the sight lines has been observed at multiple epochs, 1993/1994 and 1996. Of the thirteen stars observed twice, seven have spectra revealing changes in the equivalent width and/or velocity structure of lines, most of which arise from remnant gas. Such time variability has been reported previously for the sight lines towards HD 72089 and HD 72997 by Danks & Sembach (1995) and for HD 72127 by Hobbs et al. (1991). We have confirmed the ongoing time variability of these spectra and present new evidence of variability in the spectra of HD 73658, HD 74455, HD 75309 and HD 75821. We have tabulated Na I and Ca II absorption line information for the sight lines in our sample to serve as a benchmark for further investigations of the dynamics and evolution of the Vela SNR.Comment: 8 pages of text, 4 tables, 16 pages of figures Accepted and to be published in ApJ