26 research outputs found
In-depth mechanistic analysis including high-throughput RNA sequencing in the prediction of functional and structural cardiotoxicants using hiPSC cardiomyocytes
No full textEvotec International Gmb
Identification of a small molecule inhibitor that stalls splicing at an early step of spliceosome activation
No full textSmall molecule inhibitors of pre-mRNA splicing are important tools for identifying new spliceosome assembly intermediates, allowing a finer dissection of spliceosome dynamics and function. Here, we identified a small molecule that inhibits human pre-mRNA splicing at an intermediate stage during conversion of pre-catalytic spliceosomal B complexes into activated Bact complexes. Characterization of the stalled complexes (designated B028) revealed that U4/U6 snRNP proteins are released during activation before the U6 Lsm and B-specific proteins, and before recruitment and/or stable incorporation of Prp19/CDC5L complex and other Bact complex proteins. The U2/U6 RNA network in B028 complexes differs from that of the Bact complex, consistent with the idea that the catalytic RNA core forms stepwise during the B to Bact transition and is likely stabilized by the Prp19/CDC5L complex and related proteins. Taken together, our data provide new insights into the RNP rearrangements and extensive exchange of proteins that occurs during spliceosome activation.</jats:p
Functional magnetic ferrogels: From biosensors to regenerative medicine
No full textPolyelectrolyte gels and ferrogels (FG) are attracting special interest in biomedicine. Here we describe our experience developing functional magnetic ferrogels for regenerative medicine and magnetoimpedance biosensing for measuring stray fields of nanoparticles in FG with a multilayered sensitive element. We discuss the possibility of developing a new generation of drug delivery systems for magnetic field assisted delivery, positioning and biosensing. © 2020 Author(s).This work was supported by the RSF project 18-19-00090. We thank O.M. Samatov, B. Stadler, V.N. Lepalovskij, M.A. Korch, A.V. Svalov, D.G. Blisnets, A. Larrañaga, I. Orue, and M.N. Volochaev for support. Selected measurements were made at SGIKER UPV/EHU
L1CAM: Cell adhesion and more
No full textL1CAM is a cell adhesion molecule of the immunoglobulin superfamily which was originally discovered as a major player in the development of the nervous system. L1CAM was demonstrated to have prognostic value in different cancers and to be a promising target for anti-cancer therapy. Here we overview the present data on L1CAM structure and function, regulation of its expression, role in cancer and therapeutic potential
Mystical and Philosophical Foundations of Human Interaction
No full textThe article considers the religious and mystical views of Abu Hamid al-Gazali as one of the mystical and philosophical foundations of human interaction. The author analyses the life of the thinker, his spiritual heritage, his role in the development of religious and mystical sciences. In particular, it was established that the teachings of Gazali are one of the ideological foundations of the Nakshbandi sect, through the analysis and synthesis of mystical categories such as holat, hilvat, anjuman, din, tasavwuf, ahlak, kalb, overcoming religious and ideological contradictions. This article also addresses the teachings of al-Gazali, the period in which hid world view has taken shape and his way of life. In the first period comes the youth of Gazali, his profound study of the Koran, Hadiths, jurisprudence, logic, philosophy and other sciences, and when religious and ideological conflicts in the Islamic world have escalated, as he has participated in scientific discussions with scholars and imams. In the second period, it was analysed that Gazali live alone, far from people and in the path of Sufism. Gazali’s writings during these periods are based on the fact that communication with people is the main source from a religious, mystical, philosophical and methodological point of view
Epithelial-mesenchymal transition: focus on metastatic cascade, alternative splicing, non-coding RNAs and modulating compounds
No full textCirculating miRNAs: cell-cell communication function?
No full textNuclease resistant extracellular miRNAs have been found in all known biological fluids. The biological function of extracellular miRNAs remains questionable; however, strong evidence suggests that these miRNAs can be more than just byproducts of cellular activity. Some extracellular miRNA species might carry cell-cell signaling function during various physiological and pathological processes. In this review, we discuss the state-of-the-art in the field of intercellular miRNA transport and highlight current theories regarding the origin and the biological function of extracellular miRNAs
EVASION PROBLEM IN LINEAR DIFFERENTIAL GAME WITH GRONWALL TYPE CONSTRAINT
No full textThe main aim of this work is to present some natural applications of Gronwall type inequalities in the Differential Games. In the present, the evasion problem is studied in linear differential games when Gronwall type constraints imposed on control functions of players. The Gronwall type constraint generalizes geometrical constraint. To solve the evasion problem, we propose a particular strategy for evader and study its structure depending on the parameters. This work develops and extends the ideas of works of Isaacs, Petrosyan, Pshenichnii and other researchers, including the author. Here the new sufficient solvability conditions for evader will be proposed
Author response: Identification of a small molecule inhibitor that stalls splicing at an early step of spliceosome activation
No full text
