306 research outputs found
Extensive alternative polyadenylation during zebrafish development
The post-transcriptional fate of messenger RNAs (mRNAs) is largely dictated by their 3′ untranslated regions (3′ UTRs), which are defined by cleavage and polyadenylation (CPA) of pre-mRNAs. We used poly(A)-position profiling by sequencing (3P-seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-seq reads substantially increased and improved existing 3′ UTR annotations, resulting in confidently identified 3′ UTRs for >79% of the annotated protein-coding genes in zebrafish. mRNAs from most zebrafish genes undergo alternative CPA, with those from more than a thousand genes using different dominant 3′ UTRs at different stages. These included one of the poly(A) polymerase genes, for which alternative CPA reinforces its repression in the ovary. 3′ UTRs tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3′ UTRs are highly expressed in the ovary, yet absent in the maternally contributed RNAs of the embryo, perhaps because their 3′ UTRs are too short to accommodate a uridine-rich motif required for stability of the maternal mRNA. At 2 h post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3′ UTRs provide a resource for studying gene regulation during vertebrate development.National Institutes of Health (U.S.) (Grant GM067031)
Seeing the Soils of Meridiani Planum Through the Eyes of Pancam and Microscopic Imager
We are using data from the Pancam and Microscopic Imager (MI) on the Opportunity rover to characterize the soil grains at Meridiani Planum. We have traced individual grains in all MI images of the soils using the software application ImageJ distributed by NIH, and subsequently derived size and shape properties about the grains. The resolution of the MI is 31 microns per pixel [1] so we limit our measurements to those grains larger than about 0.3 mm in size. In cases where the grain is partially or substantially buried by other grains or finer soil particles, we do not make a measurement. False-color composites from Pancam images that cover the same location imaged by MI are made from the Left 2,5,6 (753, 535, 482 nm) filters or Right 2,7,1 (753, 1009, 430 nm) filters [2] in the Red, Green, and Blue channels, respectively. These color images are then merged with the MI images to illustrate color properties of particular grains. Pancam spectra are also extracted from grains when there is sufficient spatial coverage. in diameter. Figure 2 illustrates the dominance of these small grains at this particular location, which happens to be on the southern wall of Eagle crater. The Pancam color merge with this MI image suggests that the small spherules are more consistent with the basalt grains than the blueberries (spherulitic concretions derived from outcrop rocks [7]). The resolution of Pancam images of this location is on the order of 0.5 mm so the grains are only barely resolved. A Mossbauer measurement taken on an adjacent soil (Sol 53 Vanilla) that is composed solely of these smaller spherules (Fig 1) is consistent with a basaltic composition for the grains. Their concentration at this particular location in a brighter, elongate patch along the southeastern wall compared to elsewhere inside Eagle crater suggests wind activity favored their transport and subsequent deposition here. Their spherical shape is also possibly the result of wind action rounding them during transport, though water action cannot be ruled out
Mars Exploration Rover Pancam Multispectral Imaging of Rocks, Soils, and Dust at Gusev Crater and Meridiani Planum
Multispectral imaging from the Panoramic Camera (Pancam) instruments on the Mars Exploration Rovers Spirit and Opportunity has provided important new insights about the geology and geologic history of the rover landing sites and traverse locations in Gusev crater and Meridiani Planum. Pancam observations from near-UV to near-IR wavelengths provide limited compositional and mineralogic constraints on the presence abundance, and physical properties of ferric- and ferrous-iron bearing minerals in rocks, soils, and dust at both sites. High resolution and stereo morphologic observations have also helped to infer some aspects of the composition of these materials at both sites. Perhaps most importantly, Pancam observations were often efficiently and effectively used to discover and select the relatively small number of places where in situ measurements were performed by the rover instruments, thus supporting and enabling the much more quantitative mineralogic discoveries made using elemental chemistry and mineralogy data. This chapter summarizes the major compositionally- and mineralogically-relevant results at Gusev and Meridiani derived from Pancam observations. Classes of materials encountered in Gusev crater include outcrop rocks, float rocks, cobbles, clasts, soils, dust, rock grindings, rock coatings, windblown drift deposits, and exhumed whitish/yellowish salty soils. Materials studied in Meridiani Planum include sedimentary outcrop rocks, rock rinds, fracture fills, hematite spherules, cobbles, rock fragments, meteorites, soils, and windblown drift deposits. This chapter also previews the results of a number of coordinated observations between Pancam and other rover-based and Mars-orbital instruments that were designed to provide complementary new information and constraints on the mineralogy and physical properties of martian surface materials
A panchromatic study of BLAST counterparts: total star-formation rate, morphology, AGN fraction and stellar mass
We carry out a multi-wavelength study of individual galaxies detected by the
Balloon-borne Large Aperture Submillimeter Telescope (BLAST) and identified at
other wavelengths, using data spanning the radio to the ultraviolet (UV). We
develop a Monte Carlo method to account for flux boosting, source blending, and
correlations among bands, which we use to derive deboosted far-infrared (FIR)
luminosities for our sample. We estimate total star-formation rates for BLAST
counterparts with z < 0.9 by combining their FIR and UV luminosities. Star
formation is heavily obscured at L_FIR > 10^11 L_sun, z > 0.5, but the
contribution from unobscured starlight cannot be neglected at L_FIR < 10^11
L_sun, z < 0.25. We assess that about 20% of the galaxies in our sample show
indication of a type-1 active galactic nucleus (AGN), but their submillimeter
emission is mainly due to star formation in the host galaxy. We compute stellar
masses for a subset of 92 BLAST counterparts; these are relatively massive
objects, with a median mass of ~10^11 M_sun, which seem to link the 24um and
SCUBA populations, in terms of both stellar mass and star-formation activity.
The bulk of the BLAST counterparts at z<1 appear to be run-of-the-mill
star-forming galaxies, typically spiral in shape, with intermediate stellar
masses and practically constant specific star-formation rates. On the other
hand, the high-z tail of the BLAST counterparts significantly overlaps with the
SCUBA population, in terms of both star-formation rates and stellar masses,
with observed trends of specific star-formation rate that support strong
evolution and downsizing.Comment: Accepted for publication in the Astrophysical Journal. 44 pages, 11
figures. The SED template for the derivation of L_FIR has changed (added new
figure) and the discussion on the stellar masses has been improved. The
complete set of full-color postage-stamps can be found at
http://blastexperiment.info/results_images/moncelsi
Visible and near-infrared multispectral analysis of geochemically measured rock fragments at the Opportunity landing site in Meridiani Planum
We have used visible and near‐infrared Panoramic Camera (Pancam) spectral data acquired by the Opportunity rover to analyze 15 rock fragments at the Meridiani Planum landing site. These spectral results were then compared to geochemistry measurements made by the in situ instruments Mössbauer (MB) and Alpha Particle X‐ray Spectrometer (APXS) to determine the feasibility of mineralogic characterization from Pancam data. Our results suggest that dust and alteration rinds coat many rock fragments, which limits our ability to adequately measure the mineralogy of some rocks from Pancam spectra relative to the different field of view and penetration depths of MB and APXS. Viewing and lighting geometry, along with sampling size, also complicate the spectral characterization of the rocks. Rock fragments with the same geochemistry of sulfate‐rich outcrops have similar spectra, although the sulfate‐rich composition cannot be ascertained based upon Pancam spectra alone. FeNi meteorites have spectral characteristics, particularly ferric oxide coatings, that generally differentiate them from other rocks at the landing site. Stony meteorites and impact fragments with unknown compositions have a diverse range of spectral properties and are not well constrained nor diagnostic in Pancam data. Bounce Rock, with its unique basalt composition, is easily differentiated in the Pancam data from all other rock types at Meridiani Planum. Our Pancam analyses of small pebbles adjacent to these 15 rock fragments suggests that other rock types may exist at the landing site but have not yet been geochemically measured
Visible and near-infrared multispectral analysis of rocks at Meridiani Planum, Mars, by the Mars Exploration Rover Opportunity
Multispectral measurements in the visible and near infrared of rocks at Meridiani Planum by the Mars Exploration Rover Opportunity's Pancam are described. The Pancam multispectral data show that the outcrops of the Burns formation consist of two main spectral units which in stretched 673, 535, 432 nm color composites appear buff- and purple-colored. These units are referred to as the HFS and LFS spectral units based on higher and lower values of 482 to 535 nm slope. Spectral characteristics are consistent with the LFS outcrop consisting of less oxidized, and the HFS outcrop consisting of more oxidized, iron-bearing minerals. The LFS surfaces are not as common and appear, primarily, at the distal ends of outcrop layers and on steep, more massive surfaces, locations that are subject to greater eolian erosion. Consequently, the HFS surfaces are interpreted as a weathering rind. Further inherent spectral differences between layers and between different outcrop map units, both untouched and patches abraded by the rover's Rock Abrasion Tool, are also described. Comparisons of the spectral parameters of the Meridiani outcrop with a set of laboratory reflectance measurements of Fe^(3+)–bearing minerals show that the field of outcrop measurements plots near the fields of hematite, ferrihydrite, poorly crystalline goethite, and schwertmannite. Rind and fracture fill materials, observed intermittently at outcrop exposures, are intermediate in their spectral character between both the HFS and LFS spectral classes and other, less oxidized, surface materials (basaltic sands, spherules, and cobbles)
Metastatic Tumor Evolution and Organoid Modeling Implicate TGFBR2 as a Cancer Driver in Diffuse Gastric Cancer
Background: Gastric cancer is the second-leading cause of global cancer deaths, with metastatic disease representing the primary cause of mortality. To identify candidate drivers involved in oncogenesis and tumor evolution, we conduct an extensive genome sequencing analysis of metastatic progression in a diffuse gastric cancer. This involves a comparison between a primary tumor from a hereditary diffuse gastric cancer syndrome proband and its recurrence as an ovarian metastasis.
Results: Both the primary tumor and ovarian metastasis have common biallelic loss-of-function of both the CDH1 and TP53 tumor suppressors, indicating a common genetic origin. While the primary tumor exhibits amplification of the Fibroblast growth factor receptor 2 (FGFR2) gene, the metastasis notably lacks FGFR2 amplification but rather possesses unique biallelic alterations of Transforming growth factor-beta receptor 2 (TGFBR2), indicating the divergent in vivo evolution of a TGFBR2-mutant metastatic clonal population in this patient. As TGFBR2 mutations have not previously been functionally validated in gastric cancer, we modeled the metastatic potential of TGFBR2 loss in a murine three-dimensional primary gastric organoid culture. The Tgfbr2 shRNA knockdown within Cdh1-/-; Tp53-/- organoids generates invasion in vitro and robust metastatic tumorigenicity in vivo, confirming Tgfbr2 metastasis suppressor activity.
Conclusions: We document the metastatic differentiation and genetic heterogeneity of diffuse gastric cancer and reveal the potential metastatic role of TGFBR2 loss-of-function. In support of this study, we apply a murine primary organoid culture method capable of recapitulating in vivo metastatic gastric cancer. Overall, we describe an integrated approach to identify and functionally validate putative cancer drivers involved in metastasi
Overview of the Opportunity Mars Exploration Rover mission to Meridiani Planum: Eagle crater to Purgatory ripple
The Mars Exploration Rover Opportunity touched down at Meridiani Planum in January 2004 and since then has been conducting observations with the Athena science payload. The rover has traversed more than 5 km, carrying out the first outcrop-scale investigation of sedimentary rocks on Mars. The rocks of Meridiani Planum are sandstones formed by eolian and aqueous reworking of sand grains that are composed of mixed fine-grained siliciclastics and sulfates. The siliciclastic fraction was produced by chemical alteration of a precursor basalt. The sulfates are dominantly Mg-sulfates and also include Ca-sulfates and jarosite. The stratigraphic section observed to date is dominated by eolian bedforms, with subaqueous current ripples exposed near the top of the section. After deposition, interaction with groundwater produced a range of diagenetic features, notably the hematite-rich concretions known as ‘‘blueberries.’’ The bedrock at Meridiani is highly friable and has undergone substantial erosion by wind-transported basaltic sand. This sand, along with concretions and concretion fragments eroded from the rock, makes up a soil cover that thinly and discontinuously buries the bedrock. The soil surface exhibits both ancient and active wind ripples that record past and present wind directions. Loose rocks on the soil surface are rare and include both impact ejecta and meteorites. While Opportunity’s results show that liquid water was once present at Meridiani Planum below and occasionally at the surface, the environmental conditions recorded were dominantly arid, acidic, and oxidizing and would have posed some significant challenges to the origin of life.Additional co-authors: J Farmer, WH Farrand, W Folkner, R Gellert, TD Glotch, M Golombek, S Gorevan, JA Grant, R Greeley, J Grotzinger, KE Herkenhoff, S Hviid, JR Johnson, G Klingelhöfer, AH Knoll, G Landis, M Lemmon, R Li, MB Madsen, MC Malin, SM McLennan, HY McSween, DW Ming, J Moersch, RV Morris, T Parker, JW Rice Jr, L Richter, R Rieder, M Sims, M Smith, P Smith, LA Soderblom, R Sullivan, NJ Tosca, H Wnke, T Wdowiak, M Wolff, A Ye
Overview of the Spirit Mars Exploration Rover Mission to Gusev Crater: Landing Site to Backstay Rock in the Columbia Hills
Spirit landed on the floor of Gusev Crater and conducted initial operations on soil covered, rock-strewn cratered plains underlain by olivine-bearing basalts. Plains surface rocks are covered by wind-blown dust and show evidence for surface enrichment of soluble species as vein and void-filling materials and coatings. The surface enrichment is the result of a minor amount of transport and deposition by aqueous processes. Layered granular deposits were discovered in the Columbia Hills, with outcrops that tend to dip conformably with the topography. The granular rocks are interpreted to be volcanic ash and/or impact ejecta deposits that have been modified by aqueous fluids during and/or after emplacement. Soils consist of basaltic deposits that are weakly cohesive, relatively poorly sorted, and covered by a veneer of wind blown dust. The soils have been homogenized by wind transport over at least the several kilometer length scale traversed by the rover. Mobilization of soluble species has occurred within at least two soil deposits examined. The presence of mono-layers of coarse sand on wind-blown bedforms, together with even spacing of granule-sized surface clasts, suggest that some of the soil surfaces encountered by Spirit have not been modified by wind for some time. On the other hand, dust deposits on the surface and rover deck have changed during the course of the mission. Detection of dust devils, monitoring of the dust opacity and lower boundary layer, and coordinated experiments with orbiters provided new insights into atmosphere-surface dynamics
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