Critical Role of FLRT1 Phosphorylation in the Interdependent Regulation of FLRT1 Function and FGF Receptor Signalling

Background Fibronectin leucine rich transmembrane (FLRT) proteins have dual properties as regulators of cell adhesion and potentiators of fibroblast growth factor (FGF) mediated signalling. The mechanism by which the latter is achieved is still unknown and is the subject of this investigation. Principal Findings Here we show that FLRT1 is a target for tyrosine phosphorylation mediated by FGFR1 and implicate a non-receptor Src family kinase (SFK). We identify the target tyrosine residues in the cytoplasmic domain of FLRT1 and show that these are not direct substrates for Src kinase suggesting that the SFK may exert effects via potentiation of FGFR1 kinase activity. We show that whilst FLRT1 expression results in a ligand-dependent elevation of MAP kinase activity, a mutant version of FLRT1, defective as an FGFR1 kinase substrate (Y3F-FLRT1), has the property of eliciting ligand-independent chronic activation of the MAP kinase pathway which is suppressed by pharmacological inhibition of either FGFR1 or Src kinase. Functional investigation of FGFR1 and FLRT1 signalling in SH-SY5Y neuroblastoma cells reveals that FLRT1 alone acts to induce a multi-polar phenotype whereas the combination of FLRT1 and FGFR activation, or expression of Y3F-FLRT1, acts to induce neurite outgrowth via MAPK activation. Similar results were obtained in a dendrite outgrowth assay in primary hippocampal neurons. We also show that FGFR1, FLRT1 and activated Src are co-localized and this complex is trafficked toward the soma of the cell. The presence of Y3F-FLRT1 rather than FLRT1 resulted in prolonged localization of this complex within the neuritic arbour. Conclusions This study shows that the phosphorylation state of FLRT1, which is itself FGFR1 dependent, may play a critical role in the potentiation of FGFR1 signalling and may also depend on a SFK-dependent phosphorylation mechanism acting via the FGFR. This is consistent with an ‘in vivo’ role for FLRT1 regulation of FGF signalling via SFKs. Furthermore, the phosphorylation-dependent futile cycle mechanism controlling FGFR1 signalling is concurrently crucial for regulation of FLRT1-mediated neurite outgrowth

The Population of Weak Mg II Absorbers I. A Survey of 26 QSO HIRES/Keck Spectra

We present a search for "weak" MgII absorbers [those with W_r(2796) < 0.3 A in the HIRES/Keck spectra of 26 QSOs. We found 30, of which 23 are newly discovered. The spectra are 80% complete to W_r(2796) = 0.02 A and have a cumulative redshift path of ~17.2 for the redshift range 0.4 < z < 1.4. The number of absorbers per unit redshift, dN/dz, is seen to increase as the equivalent width threshold is decreased; we obtained dN/dz = 1.74+/-0.10 for our 0.02 <= W_r(2796) < 0.3 A sample. The equivalent width distribution follows a power law with slope -1.0; there is no turnover down to W_r(2796) = 0.02 A at = 0.9. Weak absorbers comprise at least 65% of the total MgII absorption population, which outnumbers Lyman limit systems (LLS) by a factor of 3.8+/-1.1; the majority of weak MgII absorbers must arise in sub-LLS environments. Tentatively, we predict that ~5% of the Lyman-alpha forest clouds with W_r(1215) > 0.1 A will have detectable MgII absorption to W_r,min(2796) = 0.02 A and that this is primarily a high-metallicity selection effect (Z/Z_sun] > -1). This implies that MgII absorbing structures figure prominently as tracers of sub-LLS environments where gas has been processed by stars. We compare the number density of W_r(2796) > 0.02 A absorbers with that of both high and low surface brightness galaxies and find a fiducial absorber size of 35h^-1 to 63h^-1 kpc, depending upon the assumed galaxy population and their absorption properties. The individual absorbing "clouds" have W_r(2796) <= 0.15 A and their narrow (often unresolved) line widths imply temperatures of ~25,000 K. We measured W_r(1548) from CIV in FOS/HST archival spectra and, based upon comparisons with FeII, found a range of ionization conditions (low, high, and multi-phase) in absorbers selected by weak MgII.Comment: Accepted Version: 43 pages, PostScript figures embedded; accepted to ApJ; updated version includes analysis of CIV absorptio

Observations from Preliminary Experiments on Spatial and Temporal Pressure Measurements from Near-Field Free Air Explosions

It is self-evident that a crucial step in analysing the performance of protective structures is to be able to accurately quantify the blast load arising from a high explosive detonation. For structures located near to the source of a high explosive detonation, the resulting pressure is extremely high in magnitude and highly non-uniform over the face of the target. There exists very little direct measurement of blast parameters in the nearfield, mainly attributed to the lack of instrumentation sufficiently robust to survive extreme loading events yet sensitive enough to capture salient features of the blast. Instead literature guidance is informed largely by early numerical analyses and parametric studies. Furthermore, the lack of an accurate, reliable data set has prevented subsequent numerical analyses from being validated against experimental trials. This paper presents an experimental methodology that has been developed in part to enable such experimental data to be gathered. The experimental apparatus comprises an array of Hopkinson pressure bars, fitted through holes in a target, with the loaded faces of the bars flush with the target face. Thus, the bars are exposed to the normally or obliquely reflected shocks from the impingement of the blast wave with the target. Pressure-time recordings are presented along with associated Arbitary-Langrangian-Eulerian modelling using the LS-DYNA explicit numerical code. Experimental results are corrected for the effects of dispersion of the propagating waves in the pressure bars, enabling accurate characterisation of the peak pressures and impulses from these loadings. The combined results are used to make comments on the mechanism of the pressure load for very near-field blast events

Global and regional emissions estimates for N2O

We present a comprehensive estimate of nitrous oxide (N2O) emissions using observations and models from 1995 to 2008. High-frequency records of tropospheric N2O are available from measurements at Cape Grim, Tasmania; Cape Matatula, American Samoa; Ragged Point, Barbados; Mace Head, Ireland; and at Trinidad Head, California using the Advanced Global Atmospheric Gases Experiment (AGAGE) instrumentation and calibrations. The Global Monitoring Division of the National Oceanic and Atmospheric Administration/Earth System Research Laboratory (NOAA/ESRL) has also collected discrete air samples in flasks and in situ measurements from remote sites across the globe and analyzed them for a suite of species including N2O. In addition to these major networks, we include in situ and aircraft measurements from the National Institute of Environmental Studies (NIES) and flask measurements from the Tohoku University and Commonwealth Scientific and Industrial Research Organization (CSIRO) networks. All measurements show increasing atmospheric mole fractions of N2O, with a varying growth rate of 0.1-0.7% per year, resulting in a 7.4% increase in the background atmospheric mole fraction between 1979 and 2011. Using existing emission inventories as well as bottom-up process modeling results, we first create globally gridded a priori N2O emissions over the 37 years since 1975. We then use the three-dimensional chemical transport model, Model for Ozone and Related Chemical Tracers version 4 (MOZART v4), and a Bayesian inverse method to estimate global as well as regional annual emissions for five source sectors from 13 regions in the world. This is the first time that all of these measurements from multiple networks have been combined to determine emissions. Our inversion indicates that global and regional N2O emissions have an increasing trend between 1995 and 2008. Despite large uncertainties, a significant increase is seen from the Asian agricultural sector in recent years, most likely due to an increase in the use of nitrogenous fertilizers, as has been suggested by previous studies.</p

A Strategy for a Global Observing System for Verification of National Greenhouse Gas Emissions

Abstract and PDF report are also available on the MIT Joint Program on the Science and Policy of Global Change website (http://globalchange.mit.edu/).With the risks of climate change becoming increasingly evident, there is growing discussion regarding international treaties and national regulations to lower greenhouse gas (GHG) emissions. Enforcement of such agreements is likely to depend formally upon national and sectoral emission reporting procedures (sometimes referred to as “bottom-up” methods). However, for these procedures to be credible and effective, it is essential that these reports or claims be independently verified. In particular, any disagreements between these “bottom-up” emission estimates, and independent emission estimates inferred from global GHG measurements (so-called “top-down” methods) need to be resolved. Because emissions control legislation is national or regional in nature, not global, it is also essential that “top-down” emission estimates be determined at these same geographic scales. This report lays out a strategy for quantifying and reducing uncertainties in greenhouse gas emissions, based on a comprehensive synthesis of global observations of various types with models of the global cycles of carbon dioxide and other greenhouse gases that include both the natural and human influences on these cycles. The overall goal is to establish a global observing and estimation system that incorporates all relevant available knowledge (physical, biogeochemical, technological and economic) in order to verify greenhouse gas emissions, as a key component of any global GHG treaty.Lockheed Martin Corporation and the MIT Joint Program on the Science and Policy of Global Change, which is funded by a consortium of government, industry and foundation sponsors

LBT and Spitzer Spectroscopy of Star-Forming Galaxies at 1 < z < 3: Extinction and Star Formation Rate Indicators

We present spectroscopic observations in the rest-frame optical and near- to mid-infrared wavelengths of four gravitationally lensed infrared (IR) luminous star-forming galaxies at redshift 1 < z < 3 from the LUCIFER instrument on the Large Binocular Telescope and the Infrared Spectrograph on Spitzer. The sample was selected to represent pure, actively star-forming systems, absent of active galactic nuclei. The large lensing magnifications result in high signal-to-noise spectra that can probe faint IR recombination lines, including Pa-alpha and Br-alpha at high redshifts. The sample was augmented by three lensed galaxies with similar suites of unpublished data and observations from the literature, resulting in the final sample of seven galaxies. We use the IR recombination lines in conjunction with H-alpha observations to probe the extinction, Av, of these systems, as well as testing star formation rate (SFR) indicators against the SFR measured by fitting spectral energy distributions to far-IR photometry. Our galaxies occupy a range of Av from ~0 to 5.9 mag, larger than previously known for a similar range of IR luminosities at these redshifts. Thus, estimates of SFR even at z ~ 2 must take careful count of extinction in the most IR luminous galaxies. We also measure extinction by comparing SFR estimates from optical emission lines with those from far-IR measurements. The comparison of results from these two independent methods indicates a large variety of dust distribution scenarios at 1 < z < 3. Without correcting for dust extinction, the H-alpha SFR indicator underestimates the SFR; the size of the necessary correction depends on the IR luminosity and dust distribution scenario. Individual SFR estimates based on the 6.2 micron PAH emission line luminosity do not show a systematic discrepancy with extinction, although a considerable, ~0.2 dex scatter is observed.Comment: Accepted for publication in The Astrophysical Journal; 14 pages, 8 figure

Resource Availability and Entrainment Are Driven by Offsets Between Nutriclines and Winter Mixed‐Layer Depth

While phytoplankton play a key role in ocean biogeochemical cycles, the availability and supply pathways of resources that support their growth remain poorly constrained. Here, we show that the availability of various resources varies over several orders of magnitude throughout the Atlantic Ocean, causing regional contrasts in resource deficiency. Regional variations in the relative availability of nitrogen, phosphorous, silicon, iron, zinc, manganese, cobalt, and cadmium are important and result from the contrasts between winter mixing depths and differences in vertical profiles of the different resources. The winter-time thickening of the mixed layer may replenish or deplete resources via entrainment, depending on the vertical nutrient profile. For nutrients like nitrate, phosphate, and cadmium, entrainment is a consistent source term. While for others, such as manganese and iron, entrainment can reduce ocean resource availability, particularly in subtropical regions. Any future change to the depth of winter-time mixing will cause region-specific changes in relative availability of different resources that may have important ecological consequences

Extremely Red Objects in The Lockman Hole

We investigate Extremely Red Objects (EROs) using near- and mid-infrared observations in five passbands (3.6 to 24 micron) obtained from the Spitzer Space Telescope, and deep ground-based R and K imaging. The great sensitivity of the IRAC camera allows us to detect 64 EROs in only 12 minutes of IRAC exposure time, by means of an R-[3.6] color cut (analogous to the traditional red R-K cut). A pure infrared K-[3.6] red cut detects a somewhat different population and may be more effective at selecting z > 1.3 EROs. We find 17% of all galaxies detected by IRAC at 3.6 or 4.5 micron to be EROs. These percentages rise to about 40% at 5.8 micron, and about 60% at 8.0 micron. We utilize the spectral bump at 1.6 micron to divide the EROs into broad redshift slices using only near-infrared colors (2.2/3.6/4.5 micron). We conclude that two-thirds of all EROs lie at redshift z > 1.3. Detections at 24 micron imply that at least 11% of 0.6 1.3 EROs are dusty star-forming galaxies.Comment: to appear in the special Spitzer issue of the ApJ