Press-room / Digest
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The role of natural mutations of the human protein SLURP-1 in the pathogenesis of Mal de Meleda skin disease has been determined
Researchers from the Department of Bioengineering and the Department of Structural Biology of the IBCh RAS received new functional and structural information on the role of mutations in the SLURP-1 protein in the pathogenesis of Mal de Meleda (MDM), a recessively inherited keratoderma. SLURP-1 is a paracrine regulator of keratinocyte homeostasis interacting with the α7 type nicotinic acetylcholine receptor (α7-nAChR) and it participates in control of growth, terminal differentiation, apoptosis and cornification of keratinocytes. The study showed that effect of SLURP-1 mutants on keratinocyte homeostasis depends on a location in the molecule, where the mutation is appeared. Effects can lead to mild or severe forms of Mal de Meleda, and can include changes in the antiproliferative and apoptotic properties of SLURP-1. Using the obtained functional data, model of the SLURP-1/α7-nAChR complex was built. The work was published in the Journal of Investigative Dermatology under support of the Russian Science Foundation. Learn more
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In vivo blockade of mononuclear phagocyte system with solid nanoparticles: Efficiency and affecting factors
The mononuclear phagocyte system (MPS) blockade improves the pharmacokinetics of diagnostic and therapeutic nanoparticles and reduces side toxicity. Scientists from MIPT, MEPhI, GPI and the Laboratory of molecular immunology of IBCh RAS studied the key factors that determine the effectiveness of the blockade: blocker particle dose, size, zeta potential and type of coating, as well as mouse strain, inflammation and the presence of a tumor. It was found that the type of blocker coating had the strongest effect on MPS blockade efficiency, which allowed to prolong circulation of functional nanoparticles in the bloodstream 18 times. The results obtained demonstrate the practical significance of the MPS blockade and possible mechanisms for its regulation to improve the delivery of diagnostic and therapeutic nanoagents. The work was published in the Journal of Controlled Release.
Genomic DNA i-motifs as fast sensors responsive to near-physiological pH microchanges
Researchers from Federal Research and Clinical Center of Physical-Chemical medicine and IBCh RAS, in collaboration with Russian colleagues developed simple and robust sensors for detecting microchanges in intracellular pH. The sensors are based on unusual DNA structures - i-motifs, that are found in cancer- and neudegeneration-related genes. Given their intrinsic sensitivity to minor pH changes within the physiological range, such DNA structures can be used as core elements of biocompatible sensors. Using stopped-flow techniques and FRET-melting assays, i-motifs with fast responses to pH alterations were selected. For the leading fast sensor, the labeling scheme was optimized and intracellular calibration was performed. Due to its favorable kinetic characteristics, the sensor is potentially applicable for monitoring proton dynamics in the nucleus or pH-jumps observed upon neuron activation. The research was published in the journal Biosensors and Bioelectronics. Learn more
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Pulsed laser reshaping and fragmentation of upconversion nanoparticles – from hexagonal prisms to 1D nanorods through “Medusa”-like structures
Researchers from the Federal Research Center "Crystallography and Photonics" and the Institute of Bioorganic Chemistry RAS, together with colleagues from Austria, Germany and France, have developed a technology for 1D-nanostructure fabrication. One-dimensional upconversion nanocrystals (UCNPs) with unique optical properties and morphology have been prepared by the laser-induced recrystallization of nanostate. Exposure to picosecond laser irradiation of UCNPs with a core/shell structure (β-Na1.5Y1.5F6:Yb3+, Tm3+/β-Na1.5Y1.5F6) led to a controlled dynamic nanotransformation of luminescent 3D-structure into 1D with inherent optical properties through the formation of particles with unusual “medusa”-like architecture. The proposed technology based on picosecond laser treatment enables UCNP surface hydrophilization and performs the transformation from "nano" to "nano", which ensures the preparation of nanoagents for biovisualization and therapy. The research was published in the journal Nano Research.
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From cytoskeleton to pluripotency: a new mechanism for regulating stem status of the embryonic cells
Researchers from the Laboratory of Molecular Bases of Embryogenesis (Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS), in technical cooperation with colleagues from the Department of Metabolism and Redox Biology (Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS), the Laboratory of Genomics and Epigenomics of Vertebrates in the Federal Center "Fundamentals of Biotechnology" RAS, as well as with colleagues from the Cell Motility Group of the Institute of Protein Research RAS, discovered a previously unknown mechanism of the regulation of the activity of genes that determine the pluripotent status of the embryonic stem cells. The article was published in Cell Reports. Learn more