Genes encoding subunits of SWI/SNF (BAF) chromatin-remodeling complexes are collectively mutated in ∼20% of all human cancers. Although ARID1A is the most frequent target of mutations, the mechanism ...by which its inactivation promotes tumorigenesis is unclear. Here we demonstrate that Arid1a functions as a tumor suppressor in the mouse colon, but not the small intestine, and that invasive ARID1A-deficient adenocarcinomas resemble human colorectal cancer (CRC). These tumors lack deregulation of APC/β-catenin signaling components, which are crucial gatekeepers in common forms of intestinal cancer. We find that ARID1A normally targets SWI/SNF complexes to enhancers, where they function in coordination with transcription factors to facilitate gene activation. ARID1B preserves SWI/SNF function in ARID1A-deficient cells, but defects in SWI/SNF targeting and control of enhancer activity cause extensive dysregulation of gene expression. These findings represent an advance in colon cancer modeling and implicate enhancer-mediated gene regulation as a principal tumor-suppressor function of ARID1A.
The biodiversity of deep-sea hydrothermal vents in the Indian Ocean remains poorly characterised compared with that of their Pacific and Atlantic counterparts. Although the Longqi hydrothermal vent ...field is the most extensively explored vent site on the ultra-slow-spreading Southwest Indian Ridge, it is still a source of new discoveries. Here, we report and formally describe a new peltospirid snail from Longqi - Lirapex felix sp. nov. Known from only two specimens, it differs from other named Lirapex species by a depressed spire and the lack of coil loosening on the body whorl. Examinations of the external anatomy and radular characteristics agree with its placement in Lirapex, which is also supported by a molecular phylogeny reconstructed using the barcoding fragment of the mitochondrial cytochrome c oxidase I (COI) gene. This is the fifth peltospirid snail known to inhabit the Longqi field, three of which (including Lirapex felix sp. nov.) have been found nowhere else. There is growing evidence that the Longqi field represents a biogeographically unique site among Indian Ocean vents. The discovery of Lirapex felix sp. nov. adds to the unique biodiversity of Longqi field, with implications for conservation in the light of potential deep-sea mining.
This work is registered in ZooBank under:
urn:lsid:zoobank.org:pub:3B892762-2110-4A1E-A80D-1779CBEC5EB3
ABSTRACT We present a combined analysis of the observations of the gravitational microlensing event OGLE-2015-BLG-0479 taken both from the ground and by the Spitzer Space Telescope. The light curves ...seen from the ground and from space exhibit a time offset of ∼13 days between the caustic spikes, indicating that the relative lens-source positions seen from the two places are displaced by parallax effects. From modeling the light curves, we measure the space-based microlens parallax. Combined with the angular Einstein radius measured by analyzing the caustic crossings, we determine the mass and distance of the lens. We find that the lens is a binary composed of two G-type stars with masses of ∼1.0 M and ∼0.9 M located at a distance of ∼3 kpc. In addition, we are able to constrain the complete orbital parameters of the lens thanks to the precise measurement of the microlens parallax derived from the joint analysis. In contrast to the binary event OGLE-2014-BLG-1050, which was also observed by Spitzer, we find that the interpretation of OGLE-2015-BLG-0479 does not suffer from the degeneracy between ( , ) and ( , ) solutions, confirming that the four-fold parallax degeneracy in single-lens events collapses into the two-fold degeneracy for the general case of binary-lens events. The location of the blend in the color-magnitude diagram is consistent with the lens properties, suggesting that the blend is the lens itself. The blend is bright enough for spectroscopy and thus this possibility can be checked from future follow-up observations.
In this paper, the full development and analysis of four models for the transversely vibrating uniform beam are presented. The four theories are the Euler–Bernoulli, Rayleigh, shear and Timoshenko. ...First, a brief history of the development of each beam model is presented. Second, the equation of motion for each model, and the expressions for boundary conditions are obtained using Hamilton's variational principle. Third, the frequency equations are obtained for four sets of end conditions: free–free, clamped–clamped, hinged–hinged and clamped–free. The roots of the frequency equations are presented in terms of normalized wave numbers. The normalized wave numbers for the other six sets of end conditions are obtained using the analysis of symmetric and antisymmetric modes. Fourth, the orthogonality conditions of the eigenfunctions or mode shape and the procedure to obtain the forced response using the method of eigenfunction expansion is presented. Finally, a numerical example is shown for a non-slender beam to signify the differences among the four beam models.
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