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- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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- Singh, G., et al.
(författare)
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Revealing asymmetrical dust distribution in the inner regions of HD 141569
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
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Tidskriftsartikel (refereegranskat)abstract
- Context. The combination of high-contrast imaging with spectroscopy and polarimetry offers a pathway to studying the grain distribution and properties of debris disks in exquisite detail. Here, we focus on the case of a gas-rich debris disk around HD 141569A, which features a multiple-ring morphology first identified with SPHERE in the near-infrared.Aims. We obtained polarimetric differential imaging with SPHERE in the H-band to compare the scattering properties of the innermost ring at 44 au with former observations in total intensity with the same instrument. In polarimetric imaging, we observed that the intensity of the ring peaks in the south-east, mostly in the forward direction, whereas in total intensity imaging, the ring is detected only at the south. This noticeable characteristic suggests a non-uniform dust density in the ring. With these two sets of images, we aim to study the distribution of the dust to solve for the actual dust distribution.Methods. We implemented a density function varying azimuthally along the ring and generated synthetic images both in polarimetry and in total intensity, which are then compared to the actual data. The search for the best-fit model was performed both with a grid-based and an MCMC approach. Using the outcome of this modelization, we further measured the polarized scattering phase function for the observed scattering angle between 33 degrees and 147 degrees as well as the spectral reflectance of the southern part of the ring between 0.98 and 2.1 mu m. We tentatively derived the grain properties by comparing these quantities with MCFOST models and assuming Mie scattering.Results. We find that the dust density peaks in the south-west at an azimuthal angle of 220 degrees similar to 238 degrees with a rather broad width of 61 degrees similar to 127 degrees. The difference in the intensity distributions observed in polarimetry and total intensity is the result of this particular morphology. Although there are still uncertainties that remain in the determination of the anisotropic scattering factor, the implementation of an azimuthal density variation to fit the data proved to be robust. Upon elaborating on the origin of this dust density distribution, we conclude that it could be the result of a massive collision when we account for the effect of the high gas mass that is present in the system on the dynamics of grains. In terms of grain composition, our preliminary interpretation indicates a mixture of porous sub-micron sized astro-silicate and carbonaceous grains.Conclusions. The SPHERE observations have allowed, for the first time, for meaningful constraints to be placed on the dust distribution beyond the standard picture of a uniform ring-like debris disk. However, future studies with a multiwavelength approach and additional detailed modeling would be required to better characterize the grain properties in the HD 141569 system.
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- Hinkley, Sasha, et al.
(författare)
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The JWST Early Release Science Program for the Direct Imaging and Spectroscopy of Exoplanetary Systems
- 2022
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1039
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Tidskriftsartikel (refereegranskat)abstract
- The direct characterization of exoplanetary systems with high-contrast imaging is among the highest priorities for the broader exoplanet community. As large space missions will be necessary for detecting and characterizing exo-Earth twins, developing the techniques and technology for direct imaging of exoplanets is a driving focus for the community. For the first time, JWST will directly observe extrasolar planets at mid-infrared wavelengths beyond 5 μm, deliver detailed spectroscopy revealing much more precise chemical abundances and atmospheric conditions, and provide sensitivity to analogs of our solar system ice-giant planets at wide orbital separations, an entirely new class of exoplanet. However, in order to maximize the scientific output over the lifetime of the mission, an exquisite understanding of the instrumental performance of JWST is needed as early in the mission as possible. In this paper, we describe our 55 hr Early Release Science Program that will utilize all four JWST instruments to extend the characterization of planetary-mass companions to ∼15 μm as well as image a circumstellar disk in the mid-infrared with unprecedented sensitivity. Our program will also assess the performance of the observatory in the key modes expected to be commonly used for exoplanet direct imaging and spectroscopy, optimize data calibration and processing, and generate representative data sets that will enable a broad user base to effectively plan for general observing programs in future Cycles.
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