- science news The rational design of an efficient biocatalyst for the phosphoribosylation of antiviral pyrazine-2- carboxamide derivatives
The antiviral T-1105 and T-705 (Favipiravir) compounds are inactive prodrugs that undergo metabolic transformation into the active form through phosphoribosylation in vivo. The efficiency of this process in human cells is very low, making the production of the phosphoribosylated pyrazine-2-carboxamide derivatives in vitro is a worthy challenge.
- science news The molecular mechanism of body axis induction in jawless vertebrates may differ from that described in gnathostomes
A significant proportion of modern ideas about the molecular mechanisms of body axis induction and differentiation of vertebrate embryos are based on studies of classical laboratory model objects - fishes, amphibians and mammals - that belong to only one of the two major clades of extant vertebrates - gnathostomes. In these animals, genes of Noggin family have been described as key embryonic inducers of the main body axis.
- science news The loss of the classical embryonic inducer noggin1 in cartilaginous fish may be associated with the formation of their unique skeleton
The discovery of the neural inducer Noggin1 in 1992 was one of the most important events in the history of molecular developmental biology. Subsequently, several genes of the Noggin family were discovered and described in vertebrates, which appeared as a result of genomic duplications in ancestral vertebrates and differed in their expression patterns and functional properties. A series of studies carried out at the Laboratory of Molecular Bases of Embryogenesis of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, in 2006-2020, was devoted to the study of Noggins in vertebrates. The key roles of Noggins in the regulation of intracellular signaling cascades and a wide range of developmental processes, including the development of the telencephalon unique to vertebrates, have been demonstrated.
- science news CRISPR/Cas9-mediated мultiplexed multi-allelic mutagenesis of genes located on A, B and R subgenomes of hexaploid triticale
This research, performed by the members of the Laboratory of Expression Systems and Plant Genome Modification (BIOTRON), Department of Plant Molecular Biology and Biotechnology, together with colleagues from the All-Russia Research Institute of Agricultural Biotechnology, reports the first time production of edited hexaploid triticale (× Triticosecale) through CRISPR/Cas9-mediated multiplexed induction of multilocular mutations in genes associated with starch biosynthesis.
- science news Obtaining Gene-Modified HLA-E-Expressing Feeder Cells for Stimulation of Natural Killer Cells
In response to cytomegalovirus (HCMV) infection, a pool of specialized “adaptive” NK cells with immunological memory traits develops in humans. This process is based on the recognition of HCMV peptides presented in the context of the HLA-E molecule by the activating receptor NKG2C. Using retroviral transduction, members of the Laboratory of Cell Interactions of the Immunology Department, IBCH RAS, together with colleagues from the European Medical Center, obtained K562-21E feeder cells expressing HLA-E and identified a subpopulation, whose size is associated with the magnitude of NK cell proliferative response to the presentation of the HCMV peptide. The K562-21E cells can be applied both for the accumulation of HCMV-specific NK cells and for studying the adaptive cells maturation.
- science news Multiple paralogs of foxg1, the regulator of forebrain development, in lampreys and sturgeons: the legacy of genomic duplications in the early evolution of vertebrates
The forebrain of vertebrates, including its unique rostral section, the telencephalon, provides the highest forms of nervous activity in animals and humans. The foxg1 gene has been described as one of the leading regulators of early forebrain development. It has been shown that disturbances in the expression of foxg1 lead to developmental abnormalities and a decrease in the size of the forebrain, called FOXG1 syndrome in humans.
- science news Hydrogen peroxide is not generated intracellularly in human neural spheroids during ischemia-reperfusion
Reactive oxygen species (ROS) are considered a primary source of damage during an ischemic stroke. Studies on this subject are usually performed on either cell culture or animal models, which can make it difficult to translate the results to humans. Currently, 3D neurospheroids derived from induced pluripotent stem cells (iPSCs) are proposed as an optimal alternative for modeling disease conditions.
- science news Age-dependent astrocytic atrophy and mitochondrial malfunction in human neocortex
December 25, 2023
In this groundbreaking study researchers have delved into the intricate cellular changes occurring in the brains of aging adults. The study, conducted on neocortical tissue from individuals aged 22 to 72 years, provides unprecedented insights into the impact of aging on astrocytes and neurons.
- science news A non-canonical RNAi pathway induced by externally applied virus-specific dsRNA in plants
December 7, 2023
The external application of dsRNAh has recently been developed as a new approach for crop protection. It is assumed that the mechanism of dsRNA-mediated antivirus RNA defence is similar to that of natural RNA interference (RNAi). There is, however, no direct evidence to support this idea. Scientists from the IBCh RAS in collaboration with colleagues from JHI (UK) we carried out the analysis of small RNAs (sRNA) as hallmarks of RNAi induced by potato virus Y (PVY).
- science news Redox differences between neonatal and adult cardiomyocytes under hypoxia
December 4, 2023
It is a known fact that oxidative stress plays a key role in the pathogenesis of coronary heart disease. However, why do neonatal cardiomyocytes exhibit greater resistance to hypoxia compared to adult cell types?
- science news Venom-gland transcriptomics and venom proteomics of the Tibellus oblongus spider
November 28, 2023
The Scientific Data journal published the paper “Transcriptomics of Venom Glands and Proteomics of Venom of the Spider Tibellus Oblongus,” which describes a comprehensive study of the venom of the Central Asian spider. As a result of the analysis of the transcriptome of the venom glands and the venom proteome, more than 200 new peptide molecules were discovered, including both toxins with a classical organization and with unique structural motifs.
- science news Open AccessArticle Galectin-9 as a Potential Modulator of Lymphocyte Adhesion to Endothelium via Binding to Blood Group H Glycan
September 25, 2023
Adhesion of leukocytes is a key stage in their trafficking into sites of inflammation. This process is mediated through the interaction of integrins, selectins or CD44, while the role of galectins is not completely clear. It is known that galectins are capable of interacting with oligolactosamines of endothelial cells, and also that in vitro tandem-type galectins (Gal-4, -8 and -9) bind with high affinity to glycans of the ABH blood group system. This work shows that in a cell lines system gal-9 mediates lymphocyte adhesion to endothelial cells through binding to their H-glycan, suggesting that lymphocyte adhesion to endothelium in the circulation occurs similarly and is regulated by the level of galectin-9 expression.
- science news Fractal droplets
September 11, 2023
Biological polymers (proteins, nucleic acids and their mixtures) are able to form macromolecular complexes in solution, which at a certain saturating concertation of a polymer grow in size and when crossing the diffraction limit (0.25 µm) become visible under the microscope. Such microscopically observed spherical liquid-like formations have various naming depending on a context such as: «coacervate droplets», biomolecular condensates, etc. Although these polymer droplets (especially proteinaceous) gained numerous attentions of scientist during the last century, e. g. as potential «protocells» in «the primordial soup» according to the life-origin hypothesis by Alexander Oparin, active studies of their functional roles in the living cells flourished in the recent decades.
- science news WINEGRET: а method for Wide-scale Identification of Novel and Eliminated Genes Responsible for Evolutionary Transformations
August 17, 2023
Scientists from the Laboratory of Molecular Bases of Embryogenesis at the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, in collaboration with researchers from the Kharkevich Institute for Problems of Information Transmission, Russian Academy of Sciences, have pioneered a method for wide-scale identification of genes whose loss or emergence during evolution correlates with the disappearance or emergence of distinct phenotypic or physiological traits.
- science news Hyperglycemia exacerbates ischemic stroke not through increased generation of hydrogen peroxide
August 9, 2023
Diabetes is one of the significant risk factors for ischemic stroke. Hyperglycemia exacerbates the pathogenesis of stroke, leading to more extensive cerebral damage. It is logical to assume that more extensive tissue damage during ischemia should somehow correlate with the severity of oxidative stress.
- science news New chaotropic mixtures simplify the genomic DNA preparation from fungi for PCR use
July 26, 2023
Researchers from the Laboratory of neuroreceptors and neuroregulators of IBCh RAS have improved the method of genomic DNA preparation from fungi for PCR diagnostics.
- science news Role of energy transfer in a nanoinitiator complex for upconversion-driven polymerization
July 21, 2023
The researchers from the Laboratory of Polymers for Biology, Institute of Bioorganic Chemistry RAS, together with colleagues from the Federal Scientific Research Center «Crystallography and Photonics» RAS and other institutes, have demonstrated an effective strategy for the polymerization of photocurable compositions (PCC) using a nanoinitiator based on upconversion nanoparticles (UCNPs), activated by near infrared (NIR) light.
- science news Classification of snake venoms using Raman spectroscopy
June 30, 2023
Scientists from the Department of Molecular Neuroimmune Signaling of the Institute of Bioorganic Chemistry RAS, together with colleagues from the Prokhorov General Physics Institute RAS conducted a study of various snake venoms using Raman spectroscopy and demonstrated the applicability of this method to the analysis of such complex biomolecular mixtures as venoms.
- science news Total synthesis of racemic thieno[3,2-f]thiochromene tricarboxylate, a luciferin from marine polychaete Odontosyllis undecimdonta
June 28, 2023
The researchers from the Laboratory of Chemistry of Metabolic Pathways in collaboration with colleagues from other department of IBCh RAS conducted the total synthesis of luciferin from marine polychaete Odontosyllis undecimdonta, a heterocyclic compound with a previously unknown skeleton. The research was published in Organic Letters.
- science news Effects of cobra cardiotoxins on intracellular calcium and the contracture of rat cardiomyocytes depend on their structural types
June 23, 2023
Scientists from the Department of Molecular Neuroimmune Signaling of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, together with colleagues from the Institute of Cell Biophysics and the Institute of Theoretical and Experimental Biophysics, studied the effect of cobra venom cardiotoxins on the intracellular concentration of calcium ions and the shape of rat cardiomyocytes.
- science news Intramolecular Hydrogen Bonding in N6-Substituted 2-Chloroadenosines: Evidence from NMR Spectroscopy
June 14, 2023
Two forms were found in the NMR spectra of N6-substituted 2-chloroadenosines. The proportion of the mini-form was 11–32% of the main form. It was characterized by a separate set of signals in NMR spectra. The team of scientists from IBCh RAS assumed that the mini-form arises due to an intramolecular hydrogen bond between the N6–CH proton of the substituent and the N7 atom of purine. The 15N-HMBC spectrum confirmed the presence of a hydrogen bond in the mini-form of the nucleoside and its absence in the main form. Compounds incapable of forming such a hydrogen bond were synthesized. In these compounds, either the N7 atom of the purine or the N6–CH proton of the substituent was absent. The mini-form was not found in the NMR spectra of these nucleosides, confirming the importance of the intramolecular hydrogen bond in its formation.
- science news Conjugated dienoic acid peroxides as substrates in Chaetopterus bioluminescence system
May 30, 2023
Marine polychaete worm Chaetopterus variopedatus bioluminescence mechanism investigations date back several decades. Researchers from the Laboratory of Chemistry of Metabolic Pathways, the Laboratory of Biomolecular NMR-Spectroscopy and other subdivisions of the Institute of Bioorganic Chemistry RAS, in collaboration with scientists from the Laboratory of Photobiology of the IBP SB RAS, Moscow Institute of Physics and Technology, Pacific State Medical University, and Yeshiva University (USA) have established the structures of three substrates of the Chaetopterus luciferase bioluminescence reaction. The work was published in the International Journal of Molecular Sciences.
- science news New structural data made it possible to decipher the mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein
May 23, 2023
Calcium-selective oncochannel TRPV6 is the major driver of cell proliferation in human body and its overexpression was found in some of the most severe human cancers, including leukemia, breast, prostate, colon, ovarian, thyroid, and endometrial cancers. While significant effort has been invested in the development of synthetic TRPV6 inhibitors, natural channel blockers have been largely neglected despite of their pharmacological value.
- science news Enzymatic synthesis of 2-chloropurine arabinonucleosides with chiral amino acid amides at the c6 position and an evaluation of antiproliferative activity in vitro
April 5, 2023
A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases.
- science news Doxorubicin-Loaded Polyelectrolyte Multilayer Capsules Modified with Antitumor DR5-Specific TRAIL Variant
March 29, 2023
Carriers providing active targeted delivery of anticancer drugs to tumor cells are promising for cancer chemotherapy. A team of scientists from the Laboratory of protein engineering and the Laboratory of Biomedical Materials IBCh RAS in collaboration with collegues from other Russian Institutes have developed biodegradable polyelectrolyte microcapsules which have been modified with the DR5-B ligand.