Browsing by Author "Bogush, Igor"
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Item Advanced computational method for studying molecular vibrations and spectra for symmetrical systems with many degrees of freedom, and its application to fullerene [Articol](Springer Verlag, 2017) Bogush, Igor; Ciobu, Victor; Paladi, FlorentinA computational method for studying molecular vibrations and spectra for symmetrical systems with many degrees of freedom was developed. The algorithm allows overcoming difficulties on the automation of calculus related to the symmetry determination of such oscillations in complex systems with many degrees of freedom. One can find symmetrized displacements and, consequently, obtain and classify normal oscillations and their frequencies. The problem is therefore reduced to the determination of eigenvectors by common numerical methods, and the algorithm simplifies the procedure of symmetry determination for normal oscillations. The proposed method was applied to studying molecular vibrations and spectra of the fullerene molecule C60, and the comparison of theoretical results with experimental data is drawn. The computational method can be further extended to other problems of group theory in physics with applications in clusters and nanostructured materials.Item Nedd9 restrains renal cystogenesis in Pkd1 - / - mice [Articol](2014) Bogush, Igor; Niconova, Anna S; Plotnicova, Olga V.; Serzhanova, Victoria; Efimov, Andrey; Hensley, Harvey H.; Cai, Kathy Q.; Egleston, Brian L.; Klein-Szanto, Andres; Seeger-Nukpezah, Tamina; Golemis, Erica A.Mutations inactivating the cilia-localized Pkd1 protein result in autosomal dominant polycystic kidney disease (ADPKD), a serious inherited syndrome affecting∼1 in 500 people, in which accumulation of renal cysts eventually destroys kidney function. Severity of ADPKD varies throughout the population, for reasons thought to involve differences both in intragenicPkd1mutations and in modifier alleles. The scaffolding protein NEDD9, commonly dysregulatedduring cancer progression, interacts with Aurora-A (AURKA) kinaseto control ciliary resorption, and with Src and other partners to influence proliferative signaling pathways often activated in ADPKD.We here demonstrate Nedd9 expression is deregulated in human ADPKD and a mouse ADPKD model. Although genetic ablation of Nedd9 does not independently influence cystogenesis, constitutive absence of Nedd9 strongly promotes cyst formation in the tamoxifen-inducible Pkd1fl/fl;Cre/Esr1+mouse model of ADPKD. This cystogenic effect is associated with striking morphological defects in the cilia of Pkd1−/−;Nedd9−/−mice, associated with specific loss of ciliary localization of adenylase cyclase III in the doubly mutant genotype. Ciliary phenotypes imply a failure of Aurora-A activation:Compatible with this idea, Pkd1−/−;Nedd9−/−mice had ciliary resorption defects, and treatment of Pkd1−/−mice with a clinical Aurora-Akinase inhibitor exacerbated cystogenesis. In addition, activation of the ADPKD-associated signaling effectors Src, Erk, and the mTOR effector S6 was enhanced, and Ca2+response to external stimuli was reduced, in Pkd1−/−;Nedd9−/−versus Pkd1−/−mice. Together,these results indicated an important modifier action of Nedd9 on ADPKD pathogenesis involving failure to activate Aurora-A.