The function of endocytosis in Wnt signaling

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Wnt growth factors regulate one of the most important signaling networks during development, tissue homeostasis and disease. Despite the biological importance of Wnt signaling, the mechanism of endocytosis during this process is ill described. Wnt molecules can act as paracrine signals, which are secreted from the producing cells and transported through neighboring tissue to activate signaling in target cells. Endocytosis of the ligand is important at several stages of action: One central function of endocytic trafficking in the Wnt pathway occurs in the source cell. Furthermore, the β-catenin-dependent Wnt ligands require endocytosis for signal activation and to regulate gene transcription in the responding cells. Alternatively, Wnt/β-catenin-independent signaling regulates endocytosis of cell adherence plaques to control cell migration. In this comparative review, we elucidate these three fundamental interconnected functions, which together regulate cellular fate and cellular behavior. Based on established hypotheses and recent findings, we develop a revised picture for the complex function of endocytosis in the Wnt signaling network.Funding was provided by Deutsche Forschungsgemeinschaft (Grant no. SCHO847-5) and the University of Exeter (GB) (LSI Start-up Grant)

Warm HCN, C2H2, and CO in the disk of GV Tau

We present the first high-resolution, ground-based observations of HCN and C2H2 toward the T Tauri binary star system GV Tau. We detected strong absorption due to HCN nu_3 and weak C2H2 (nu_3 and nu_2 + (nu_4 + nu_5)^0_+) absorption toward the primary (GV Tau S) but not the infrared companion. We also report CO column densities and rotational temperatures, and present abundances relative to CO of HCN/CO ~0.6% and C2H2/CO ~1.2% and an upper limit for CH4/CO < 0.37% toward GV Tau S. Neither HCN nor C2H2 were detected toward the infrared companion and results suggest that abundances may differ between the two sources.Comment: 23 pages, 6 figures, accepted by Ap

CO Abundance Variations in the Orion Molecular Cloud

Infrared stellar photometry from 2MASS and spectral line imaging observations of 12CO and 13CO J = 1-0 line emission from the FCRAO 14m telescope are analysed to assess the variation of the CO abundance with physical conditions throughout the Orion A and Orion B molecular clouds. Three distinct Av regimes are identified in which the ratio between the 13CO column density and visual extinction changes corresponding to the photon dominated envelope, the strongly self-shielded interior, and the cold, dense volumes of the clouds. Within the strongly self-shielded interior of the Orion A cloud, the 13CO abundance varies by 100% with a peak value located near regions of enhanced star formation activity. The effect of CO depletion onto the ice mantles of dust grains is limited to regions with AV > 10 mag and gas temperatures less than 20 K as predicted by chemical models that consider thermal-evaporation to desorb molecules from grain surfaces. Values of the molecular mass of each cloud are independently derived from the distributions of Av and 13CO column densities with a constant 13CO-to-H2 abundance over various extinction ranges. Within the strongly self-shielded interior of the cloud (Av > 3 mag), 13CO provides a reliable tracer of H2 mass with the exception of the cold, dense volumes where depletion is important. However, owing to its reduced abundance, 13CO does not trace the H2 mass that resides in the extended cloud envelope, which comprises 40-50% of the molecular mass of each cloud. The implied CO luminosity to mass ratios, M/L_{CO}, are 3.2 and 2.9 for Orion A and Orion B respectively, which are comparable to the value (2.9), derived from gamma-ray observations of the Orion region. Our results emphasize the need to consider local conditions when applying CO observations to derive H2 column densities.Comment: Accepted for publication in MNRAS. 21 pages, 14 figure

A multiwavelength study of embedded clusters in W5-east, NGC 7538, S235, S252 and S254-S258

articleWe present Spitzer, near-IR (NIR) and millimetre observations of the massive star-forming regions W5-east, S235, S252, S254-S258 and NGC 7538. Spitzer data is combined with NIR observations to identify and classify the young population while 12CO and 13CO observations are used to examine the parental molecular cloud. We detect in total 3021 young stellar objects (YSOs). Of those, 539 are classified as Class I, and 1186 as Class II sources. YSOs are distributed in groups surrounded by a more scattered population. Class I sources are more hierarchically organized than Class II and associated with the most dense molecular material. We identify in total 41 embedded clusters containing between 52 and 73 per cent of the YSOs. Clusters are in general non-virialized, turbulent and have star formation efficiencies between 5 and 50 per cent. We compare the physical properties of embedded clusters harbouring massive stars (MEC) and low-mass embedded clusters (LEC) and find that both groups follow similar correlations where the MEC are an extrapolation of the LEC. The mean separation between MEC members is smaller compared to the cluster Jeans length than for LEC members. These results are in agreement with a scenario where stars are formed in hierarchically distributed dusty filaments where fragmentation is mainly driven by turbulence for the more massive clusters. We find several young OB-type stars having IR-excess emission which may be due to the presence of an accretion disc.This work is based in part on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, Caltech, under a contract with NASA. Support for this work was provided by NASA through a contract issued by JPL/Caltech. We also thank NOAO for their student thesis support. The Five College Radio Astronomy Observatory was supported by NSF grant AST 0540852. CB is supported by an RCUK Fellowship at the University of Exeter, UK. This work is based in part on the IRAC postBCD processing software ‘IRACPROC’ developed by Mike Schuster, Massimo Marengo and Brian Patten at the Smithsonian Astrophysical Observatory. This research used the facilities of the Canadian Astronomy Data Centre operated by the National Research Council of Canada with the support of the Canadian Space Agency. This research has made use of the NASA/ IPAC Infrared Science Archive, which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration. We thank the Spanish MINECO for funding support from grants CSD2009-00038, AYA2009-07304 and AYA2012-32032

Development of a multimedia tutorial to educate how to assess the critical view of safety in laparoscopic cholecystectomy using expert review and crowd-sourcing

We sought to determine the feasibility of developing a multimedia educational tutorial to teach learners to assess the critical view of safety using input from expert surgeons, non-surgeons and crowd-sourcing. We intended to develop a tutorial that would teach learners how to identify the basic anatomy and physiology of the gallbladder, identify the components of the critical view of safety criteria, and understand its significance for performing a safe gallbladder removal. Using rounds of assessment with experts, laypersons and crowd-workers we developed an educational video with improving comprehension after each round of revision. We demonstrate that the development of a multimedia educational tool to educate learners of various backgrounds is feasible using an iterative review process that incorporates the input of experts and crowd sourcing. When planning the development of an educational tutorial, a step-wise approach as described herein should be considered

From top to bottom: Cell polarity in Hedgehog and Wnt trafficking.

This is the final version of the article. Available from the publisher via the DOI in this record.Spatial organization of membrane domains within cells and cells within tissues is key to the development of organisms and the maintenance of adult tissue. Cell polarization is crucial for correct cell-cell signalling, which, in turn, promotes cell differentiation and tissue patterning. However, the mechanisms linking internal cell polarity to intercellular signalling are just beginning to be unravelled. The Hedgehog (Hh) and Wnt pathways are major directors of development and their malfunction can cause severe disorders like cancer. Here we discuss parallel advances into understanding the mechanism of Hedgehog and Wnt signal dissemination and reception. We hypothesize that cell polarization of the signal-sending and signal-receiving cells is crucial for proper signal spreading and activation of the pathway and, thus, fundamental for development of multicellular organisms.SS and LB funding was provided by the University of Exeter, UK (LSI Start-up Grant awarded to SS). ACG and DSH are funded on a Young Investigator Grant (BFU2015-73609-JIN) to ACG from MINECO (Spain). DSH was also funded by a collaboration short-term EMBO fellowship. The authors would like to thank Isabel Guerrero (University of Madrid) for her respective valuable comments that helped improve the quality of the manuscript

Characterizing precursors to stellar clusters with Herschel

Context. Despite their profound effect on the universe, the formation of massive stars and stellar clusters remains elusive. Recent advances in observing facilities and computing power have brought us closer to understanding this formation process. In the past decade, compelling evidence has emerged that suggests infrared dark clouds (IRDCs) may be precursors to stellar clusters. However, the usual method for identifying IRDCs is biased by the requirement that they are seen in absorption against background mid-IR emission, whereas dust continuum observations allow cold, dense pre-stellar-clusters to be identified anywhere. Aims: We aim to understand what dust temperatures and column densities characterize and distinguish IRDCs, to explore the population of dust continuum sources that are not IRDCs, and to roughly characterize the level of star formation activity in these dust continuum sources. Methods: We use Hi-GAL 70 to 500 $m data to identify dust continuum sources in the ell = 30deg and ell = 59deg Hi-GAL science demonstration phase (SDP) fields, to characterize and subtract the Galactic cirrus emission, and perform pixel-by-pixel modified blackbody fits on cirrus-subtracted Hi-GAL sources. We utilize archival Spitzer data to indicate the level of star-forming activity in each pixel, from mid-IR-dark to mid-IR-bright. Results: We present temperature and column density maps in the Hi-GAL ell = 30deg and ell = 59deg SDP fields, as well as a robust algorithm for cirrus subtraction and source identification using Hi-GAL data. We report on the fraction of Hi-GAL source pixels which are mid-IR-dark, mid-IR-neutral, or mid-IR-bright in both fields. We find significant trends in column density and temperature between mid-IR-dark and mid-IR-bright pixels; mid-IR-dark pixels are about 10 K colder and have a factor of 2 higher column density on average than mid-IR-bright pixels. We find that Hi-GAL dust continuum sources span a range of evolutionary states from pre- to star-forming, and that warmer sources are associated with more star formation tracers. Additionally, there is a trend of increasing temperature with tracer type from mid-IR-dark at the coldest, to outflow/maser sources in the middle, and finally to 8 and 24$m bright sources at the warmest. Finally, we identify five candidate IRDC-like sources on the far-side of the Galaxy. These are cold (20 K), high column density (N(H$_2$) gt 10$^22$ cm$^-2$) clouds identified with Hi-GAL which, despite bright surrounding mid-IR emission, show little to no absorption at 8 $m. These are the first inner Galaxy far-side candidate IRDCs of which the authors are aware. Herschel in an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation by NASA.The FITS files discussed in the paper would be released publicly WITH the Hi-GAL data (on the Hi-GAL website) when the Hi-GAL data is released publicly.Peer reviewe

Assessment of NASA Airborne Laser Altimetry Data Using Ground-Based GPS Data Near Summit Station, Greenland

A series of NASA airborne lidars have been used in support of satellite laser altimetry missions. These airborne laser altimeters have been deployed for satellite instrument development, for spaceborne data validation, and to bridge the data gap between satellite missions. We used data from ground-based Global Positioning System (GPS) surveys of an 11 km long track near Summit Station, Greenland, to assess the surface–elevation bias and measurement precision of three airborne laser altimeters including the Airborne Topographic Mapper (ATM), the Land, Vegetation, and Ice Sensor (LVIS), and the Multiple Altimeter Beam Experimental Lidar (MABEL). Ground-based GPS data from the monthly ground-based traverses, which commenced in 2006, allowed for the assessment of nine airborne lidar surveys associated with ATM and LVIS between 2007 and 2016. Surface–elevation biases for these altimeters – over the flat, ice-sheet interior – are less than 0.12 m, while assessments of measurement precision are 0.09 m or better. Ground-based GPS positions determined both with and without differential post-processing techniques provided internally consistent solutions. Results from the analyses of ground-based and airborne data provide validation strategy guidance for the Ice, Cloud, and land Elevation Satellite 2 (ICESat-2) elevation and elevation-change data products