Press-room / Digest
New rigid nicotine analogues are potent ligands of nicotinic receptors
Malfunctioning of nicotinic acetylcholine receptors (nAChRs) is observed in various mental and neurodegenerative diseases, therefore, the search and design of nAChR ligands is of particular interest. Researchers from the Department of Molecular Neuroimmune Signalling of IBCH, Russian Academy of Sciences in collaboration with colleagues from the University of Florence (Italy) designed new nicotine analogues and revealed their high affinity for α4β2 and α7 nAChRs using radioligand binding assay. In the electrophysiological and calcium imaging experiments some selected compounds showed α7 and α3β2 agonistic properties, while on the α4β2, compounds 1a and 2a behaved as antagonists. Results of the study are published in Journal of Medicinal Chemistry.
Transcription factor Foxp1 plays important role in Treg
Regulatory T cells (Treg) is subpopulation of T helper lymphocytes which possesses immune suppressive properties. Treg are critical in protection from excessive immune response and autoimmunity. Unique functions of Treg are defined by transcription factor Fop3 that controls Treg-specific expression of genes. Dr. Yury Rubtsov from the Dept. of functioning of living systems in cooperation with colleagues from the Memorial Sloan-Kettering Cancer Center (New York City) studied a role of Foxp3-related protein, Foxp1, specifically in the murine Treg. In the absence of Foxp1, Treg displayed distorted Foxp3 chromatin binding which led to decreased sensitivity of the cells to IL-2 and diminished suppressive capacity. Results of the study are published in Nature Immunology.
Adaptive immune response of identical twins to live vaccine
T-cell receptors (TCRs) play a key role in adaptive immunity. TCR repertoire is very diverse and unique to each individual because it forms in the stochastic DNA recombination process. The group of scientists from the Department of genomics of adaptive immunity in collaboration with ENS (Paris, France) studied TCR repertoires of identical twins after immunization with a live vaccine. In each donor, they identified about a thousand different T-cell clones responding to immunization. Responding clones have almost unique repertoire in each donor with higher overlap in identical twin pairs. The study was supported by RSF and published in Proceedings of the National Academy of Sciences.
Chemogenetic model of cardiac insufficiency
Researchers from Molecular technologies laboratory (IBCh) in collaboration with Harvard medical school scientists developed a novel model of cardiac dysfunction caused by oxidative stress. This model is based on chemogenetics principles — enzymatic production of reactive oxygen species (ROS), stimulated by an external chemical substrate, and visualised by transgenic ROS sensor HyPer. The study is supported by Russian science foundation and published in Nature Communications.
Ras-dva: make regeneration great again
The researchers from Laboratory of molecular bases of embryogenesis recently hypothesised that the decrease of limb regeneration capacity in amniotes (reptiles, birds and mammals) could be caused by elimination in evolution of genes, encoding for important regulators of specific wound epithelium and blastema organization, which are used by excellent regenerating anamniotes (fish and amphibia). Using two anamniotic model organisms Danio rerio adult fishes and Xenopus laevis tadpoles the authors have shown the essential role of Ras-dva small GTPases in regulation of these processes, meanwhile their genes are eliminated in a stepwise manner during evolution till total absence in placental mammals. The obtained results support the hypothesis. The investigation is published in Scientific reports.