102 research outputs found
UIT Astro-2 Observations of NGC 4449
The bright Magellanic irregular galaxy NGC 4449 was observed by the
Ultraviolet Imaging Telescope (UIT) during the Astro-2 Spacelab mission in
March, 1995. Far ultraviolet (FUV) images at a spatial resolution of ~3 arcsec
show bright star-forming knots that are consistent with the general optical
morphology of the galaxy and are often coincident with bright H II regions.
Comparison of FUV with H-alpha shows that in a few regions, sequential star
formation may have occurred over the last few Myr. The bright star forming
complexes in NGC 4449 are superposed on a smooth, diffuse FUV background that
may be associated with the H-alpha "froth."Comment: 4 pages, Latex with AIP proceedings macros, 2 EPS figures. To appear
in proceedings of U. Maryland October Astrophysics Conf., 1996, AIP pu
Ultraviolet Signposts of Resonant Dynamics in the Starburst-Ringed Sab Galaxy, M94 (NGC 4736)
M94 (NGC 4736) is investigated using images from the Ultraviolet Imaging
Telescope (FUV-band), Hubble Space Telescope (NUV-band), Kitt Peak 0.9-m
telescope (H-alpha, R, and I bands), and Palomar 5-m telescope (B-band), along
with spectra from the International Ultraviolet Explorer and Lick 1-m
telescopes. The wide-field UIT image shows FUV emission from (a) an elongated
nucleus, (b) a diffuse inner disk, where H-alpha is observed in absorption, (c)
a bright inner ring of H II regions at the perimeter of the inner disk (R = 48
arcsec. = 1.1 kpc), and (d) two 500-pc size knots of hot stars exterior to the
ring on diametrically opposite sides of the nucleus (R= 130 arcsec. = 2.9 kpc).
The HST/FOC image resolves the NUV emission from the nuclear region into a
bright core and a faint 20 arcsec. long ``mini-bar'' at a position angle of 30
deg. Optical and IUE spectroscopy of the nucleus and diffuse inner disk
indicates an approximately 10^7 or 10^8 yr-old stellar population from
low-level starbirth activity blended with some LINER activity. Analysis of the
H-alpha, FUV, NUV, B, R, and I-band emission along with other observed tracers
of stars and gas in M94 indicates that most of the star formation is being
orchestrated via ring-bar dynamics involving the nuclear mini-bar, inner ring,
oval disk, and outer ring. The inner starburst ring and bi-symmetric knots at
intermediate radius, in particular, argue for bar-mediated resonances as the
primary drivers of evolution in M94 at the present epoch. Similar processes may
be governing the evolution of the ``core-dominated'' galaxies that have been
observed at high redshift. The gravitationally-lensed ``Pretzel Galaxy''
(0024+1654) at a redshift of approximately 1.5 provides an important precedent
in this regard.Comment: revised figure 1 (corrected coordinate labels on declination axis);
19 pages of text + 19 figures (jpg files); accepted for publication in A
Far Ultraviolet Imagery of the Edge-On Spiral Galaxy NGC 4631
Far ultraviolet FUV imagery of the edge-on, Sc/SBd galaxy, NGC 4631 reveals
very strong FUV emission, resulting from active star formation, uniformly
distributed along the galactic mid- plane. Multi-band imagery, HI and HII
position-velocity curves and extinction considerations all imply that the
emission is from the outer edges of the visible galaxy. The overall FUV
morphology of this edge-on disk system is remarkably similar to those of the
so-called "chain galaxies" evident at high redshift, thus suggesting a similar
interpretation for at least some of those distant objects. FUV, U, B and V
magnitudes, measured for 48 star forming regions, along with corresponding
H-alpha and H-beta measurements are used to construct diagnostic color-color
diagrams. Although there are significant exceptions, most of the star forming
regions are less massive and older than 30 Doradus. Comparison with the
expectations from two star formation models yields ages of 2.7 to 10 Myr for
the instantaneous burst (IB) model and star formation cut-off ages of 0 to 9
Myr for the continuous star formation (CSF) model. Interpreted in terms of the
IB model the photometry implies a total created mass in the 48 star forming
regions of 25 million solar-masses. When viewed as resulting from constant star
formation the photometry implies a star formation rate of 0.33 solar-masses/yr.
These results are compared to those derived from FIR and radio observations.
Corrections for FUV emission reprocessed by interstellar grains are estimated.Comment: 29 pages including 6 encapsulated Postscript figures; accepted for
publication in ApJ; changed table forma
Increased peri-ductal collagen micro-organization may contribute to raised mammographic density
BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users
Timing is everything: the regulation of type III secretion
Type Three Secretion Systems (T3SSs) are essential virulence determinants of many Gram-negative bacteria. The T3SS is an injection device that can transfer bacterial virulence proteins directly into host cells. The apparatus is made up of a basal body that spans both bacterial membranes and an extracellular needle that possesses a channel that is thought to act as a conduit for protein secretion. Contact with a host-cell membrane triggers the insertion of a pore into the target membrane, and effectors are translocated through this pore into the host cell. To assemble a functional T3SS, specific substrates must be targeted to the apparatus in the correct order. Recently, there have been many developments in our structural and functional understanding of the proteins involved in the regulation of secretion. Here we review the current understanding of protein components of the system thought to be involved in switching between different stages of secretion
Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWAS for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally-diverse individuals (European, African, Asian and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n=109,122 individuals. We identified 59 sentinel variants (p-value OBFC1indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated our TL polygenic trait scores (PTS) were associated with increased risk of cancer-related phenotypes
COSORE: A community database for continuous soil respiration and other soil‐atmosphere greenhouse gas flux data
Globally, soils store two to three times as much carbon as currently resides in the atmosphere, and it is critical to understand how soil greenhouse gas (GHG) emissions and uptake will respond to ongoing climate change. In particular, the soil‐to‐atmosphere CO2 flux, commonly though imprecisely termed soil respiration (RS), is one of the largest carbon fluxes in the Earth system. An increasing number of high‐frequency RS measurements (typically, from an automated system with hourly sampling) have been made over the last two decades; an increasing number of methane measurements are being made with such systems as well. Such high frequency data are an invaluable resource for understanding GHG fluxes, but lack a central database or repository. Here we describe the lightweight, open‐source COSORE (COntinuous SOil REspiration) database and software, that focuses on automated, continuous and long‐term GHG flux datasets, and is intended to serve as a community resource for earth sciences, climate change syntheses and model evaluation. Contributed datasets are mapped to a single, consistent standard, with metadata on contributors, geographic location, measurement conditions and ancillary data. The design emphasizes the importance of reproducibility, scientific transparency and open access to data. While being oriented towards continuously measured RS, the database design accommodates other soil‐atmosphere measurements (e.g. ecosystem respiration, chamber‐measured net ecosystem exchange, methane fluxes) as well as experimental treatments (heterotrophic only, etc.). We give brief examples of the types of analyses possible using this new community resource and describe its accompanying R software package
Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.
Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels
Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors
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