The expression of RNA-binding proteins and their interaction with the spliced pre-mRNA are the key factors in determining the final isoform profile. Transmembrane protein CD44 is involved in ...differentiation, invasion, motility, growth and survival of tumor cells, and is also a commonly accepted marker of cancer stem cells and epithelial-mesenchymal transition. However, the functions of the isoforms of this protein differ significantly. In this paper, we developed a method based on the boosted beta regression algorithm for identification of the significant RNA-binding proteins in the splicing process by modeling the isoform ratio. The application of this method to the analysis of CD44 splicing in colorectal cancer cells revealed 20 significant RNA-binding proteins. Many of them were previously shown as EMT regulators, but for the first time presented as potential CD44 splicing factors.
Regulation of alternative splicing is carried out by RNA-binding proteins. Each alternative splicing event is controlled by several RNA-binding proteins, which in combination create the distribution ...of alternative splicing products in a given cell type. Transmembrane protein CD44 plays an important role at various stages of the metastatic cascade and is considered as a promising molecule for the therapy of tumor diseases and the construction of prognostic classifiers. However, the functions of specific isoforms of this protein may differ significantly. In this work, we performed a bioinformatic search of RNA-binding proteins that can determine the expression of clinically significant isoforms 3 and 4 of CD44 protein. The analysis revealed five RNA-binding proteins, three of which (OAS1, ZFP36L2, and DHX58) are shown for the first time as potential regulators of the studied process.
We explored the dynamic response of a vortex core in a circular nanomagnet by manipulating its dipole-dipole interaction with another vortex core confined locally on top of the nanomagnet. A clear ...frequency splitting is observed corresponding to the gyrofrequencies of the two vortex cores. The peak positions of the two resonance frequencies can be engineered by controlling the magnitude and direction of the external magnetic field. Both experimental and micromagnetic simulations show that the frequency spectra for the combined system is significantly dependent on the chirality of the circular nanomagnet and is asymmetric with respect to the external bias field. We attribute this result to the strong dynamic dipole-dipole interaction between the two vortex cores, which varies with the distance between them. The possibility of having multiple states in a single nanomagnet with vertical coupling could be of interest for magnetoresistive memories.
Detection of colorectal cancer biomarkers (CRC) remains an urgent task for the diagnosis and prediction of the disease course. A promising approach is the study of cancer stem cell markers. The cell ...surface glycoprotein CD44 is very important for CRC and its stem cells. Alternative splicing of 9 variable exons of
CD44
mRNA leads to the formation of various isoforms of the protein with different roles in the progression of cancer. Studies of the functions of CD44 isoforms require adequate models considering the distribution of CD44 isoforms in real tumor samples. In the present study, the expression profile of CD44 isoforms in CRC was assessed based on the publicly available mRNA sequencing data of patient tumors from the TCGA-COAD database. It was shown that normal tissues predominantly expressed isoforms 3 and 4 at nearly equal levels, whereas tumors mainly expressed isoforms 2, 3, and 4; isoform 3 was expressed at the highest level. Further, the most relevant cell lines for studying the role of CD44 in CRC were identified based on the analysis of mRNA sequencing data of 55 CRC cell lines form CCLE database.
In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a ...uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.
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