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• Redox differences between neurons and astrocytes in vivo in ischemic brain tissues of rodents May 21

  Combinations of novel in vivo approaches allow to detail redox events with high spatiotemporal resolution in the brain tissues of laboratory animals. We demonstrated redox differences between neurons and astrocytes in damaged brain areas of rodents in vivo during ischemic stroke in model of middle cerebral artery occlusion in rats and photothrombosis model in mice. Using highly sensitive genetically encoded biosensor HyPer7 and a fiber-optic neurointerface technology, we demonstrated that astrocytes differ from neurons in elevated hydrogen peroxide levels in the ischemic brain area of rats. Raman microspectroscopy also revealed the overloading of the mitochondrial electron transport chain precisely in astrocytes in the brain tissues of awake mice during acute ischemia. The results are published in Antioxidants & Redox Signaling.

• Autophagy activator with AMPK-mediated mechanism of action May 19

  Age-related imbalance between synthesis and degradation of biomolecules in cells leads to the development of, among other, neurodegenerative diseases and diabetes. A decrease in autophagy, a process that is involved in degradation of damaged or dysfunctional cellular components, may contribute to this imbalance. Autophagy is regulated within cells through multiple signaling pathways, including the AMPK (AMP-activated protein kinase)-dependent pathway, which functions as a key sensor of changes in the cell's energy status. Researchers from the IBCh RAS, the A.N. Belozersky Institute of Physicochemical Biology of Moscow State University, the Patrice Lumumba Peoples' Friendship University of Russia, and other institutes assessed the ability of phenoxazine derivatives to activate this process. The lead compound demonstrated specific activation via the AMPK-dependent pathway and low cytotoxicity in three non-cancer cell lines. The work was published in Bioorganic Chemistry.

• Plasma protein corona of liposomes loaded with a phospholipid–allocolchicinoid conjugate enhances their anti-inflammatory potential May 12

  The staff of the Laboratory of Lipid Chemistry IBCh RAS, together with colleagues from Nizhny Novgorod State University and the Human Proteome Center of the Institute of Biomedical Chemistry, studied the effects of protein coronas formed in human blood plasma ex vivo on different liposomes carrying a colchicine analog. Today colchicine is considered as a possible treatment for cardiovascular complications. On a model of monocytes from human peripheral blood, the protein coronas have been shown to enhance the anti-inflammatory potential of liposomes. A particularly sharp effect was observed for liposomes bearing specific proteins, including minor ones in normal plasma.

• TLR2 and Zinc: A Surprising Partnership in Immune Signaling March 31

  A team of scientists from the Laboratory of Biomolecular NMR Spectroscopy at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, in collaboration with researchers from China, has made a breakthrough in understanding the function of Toll-like receptor 2 (TLR2), a key component of the innate immune system. Their study, published in FEBS Letters, reveals that TLR2 exhibits a previously unknown ability to bind zinc ions with high affinity and specificity. Toll-like receptors (TLRs) serve as the first line of defense in the immune system by recognizing pathogens and initiating immune responses. Despite extensive research, the precise molecular mechanisms governing TLR activation remain elusive. The newly identified zinc-binding capability of TLR2 provides fresh insights into its regulatory mechanisms. The researchers also identified specific amino acids essential for zinc coordination and TLR2 function, highlighting a potential link between zinc homeostasis and immune activation. These findings suggest that zinc plays a critical role in modulating TLR-mediated immune signaling, opening new avenues for research into immune system regulation and potential therapeutic applications.

• Potent painkiller from spider venom March 6

  A whole family of peptides with completely unexpected activity has been discovered in spider venom. These peptides inhibit mammalian purinergic receptors with high affinity and selectivity. A peptide called purotoxin-6 (PT6) from the venom of the crab spider Thomisus onustus inhibits P2X3 receptors, an important pharmacological target in a number of pain syndromes and chronic cough. PT6 has a compact fold and exhibits a potent analgesic effect in animal models of osteoarthritis and trigeminal neuralgia. At the same time, unlike small-molecule P2X3 ligands that are being developed as drugs, purotoxin does not cause dysgeusia, i.e., distortion of the sense of taste. Research on purotoxins began at the Institute of Bioorganic Chemistry some 20 years ago under the supervision of Academician Eugene Grishin and was successfully continued by Alexander Vassilevski. The results, unique on a global scale, were published in Molecular Therapy.

• On Selectivity of K+-channels: How Do Proteins Know About the Square Antiprism? February 24

  Potassium channels are one of the major players in the transduction of the nerve impulse, and mutations in their genes lead to neurological and cardiovascular diseases. The most important feature of K+-channels is their highest selectivity for K+ over Na+ and other cations. In the new work, members of the Group of in silico Analysis of Membrane Proteins Structure and the Laboratory of Molecular Instruments for Neurobiology analyzed all known 3D-structures of membrane proteins. As a result, the key principle of K+-channel selectivity filter architecture was confirmed: within it, oxygen atoms of the protein backbone are arranged in a chain of square antiprisms, replicating exactly the solvation geometry of the potassium ion. Distortion of the filter, for example during inactivation, is detected by the algorithm developed by the authors, which can be used for structural classification.

• Breakthrough in Preeclampsia Modeling: From 2D Cultures to Placenta-on-a-Chip February 5

  Preeclampsia is a serious pregnancy complication characterized by hypertension and multi-organ involvement in pregnant women. This condition occurs in 2–8% of all pregnancies and remains one of the leading causes of maternal and perinatal mortality. Despite decades of research, the exact mechanisms of its development are not fully understood, and existing therapeutic strategies remain only partially effective. A new study published by a team of Russian scientists led by Evgeny Knyazev, Polina Vishnyakova, Olga Lazareva, and Alexander Tonevitsky provides an overview of modern cellular models of preeclampsia and their potential in the search for new diagnostic and therapeutic approaches.

• Alexander Vassilevski is elected as the Chair of the European Section of the International Society on Toxinology December 4, 2024

  The International Society on Toxinology (IST) unites scientists and clinicians studying venoms, poisons, and toxins from all over the world. The society was founded in 1962. It organizes world and regional congresses, publishes the journal Toxicon, and sponsors the prestigious Redi Award.

• Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline November 18, 2024

  A duplication of the chromosomal region 2q23.q23.2, carrying LYPD6 and LYPD6B genes, leads to intellectual disability and autistic features. Researchers from the Neurotransmitter and Neuroreceptor Bioengineering Laboratory, Shemyakin-Ovchnnikov Institute of Bioorganic Chemistry of RAS together with colleagues from Lomonosov State University and Institute for Biomedical Problems of RAS, used a mouse model to study the consequences of overexpression of the Lypd6 and Lypd6b proteins in the brain, which is typical for patients with autism and other neuropsychiatric disorders.

• Origin, Evolution and Diversity of φ29-like Phages October 11, 2024

  The application of the definition of taxonomic species to the description of evolutionary history of biological objects with chimeric genomes is a difficult task. The limited period of the existence of species and the lability of viral genomes can also make attempts to reconstruct the evolutionary history almost pointless. The processes of genetic exchange seem to be especially pronounced in temperate phages, but genetic rearrangements between evolutionarily close groups of phages can also affect φ29-like phages. However, we can try to plot the evolutionary traits of genes encoding separate essential proteins and their stable complexes.

• Two-dimensional high-throughput on-cell screening of immunoglobulins against broad antigen repertoires July 12, 2024

  Identifying high-affinity antibodies in human blood serum is a non-trivial task due to the extremely small number of circulating B-cells with the specified specificity. A team of scientists from the IBCh RAS proposed an effective approach that allows for the identification of high-affinity antibodies against pathogen proteins while simultaneously mapping epitopes, even in the absence of information about the structure of the pathogen's immunogens. To screen therapeutic antibodies in the blood of recovered donors, only the pathogen's transcriptome is needed to create a polypeptide library of antigens displayed on the surface of a bacteriophage. The work was published in the journal Communications Biology.

• Synthesis of Substituted 1,2,4-Triazole-3-Thione Nucleosides Using E. coli Purine Nucleoside Phosphorylase July 4, 2024

  Scientists from the departments of biotechnology and structural biology (IBCH RAS) and Institute of the Chemistry of Plant Substances (Uzbekistan), and D. I. Ivanovsky Institute of Virology synthesized a series of substituted 1,2,4-triazole-3-thione nucleoside analogs and tested their antiviral activity against herpes simplex virus.

• “Molecular portraits” characterized functional states of TRPV ion channels June 28, 2024

  TRPV ion channels realize a huge variety of functions in the human body participating in the temperature and pain sensation, cell division, calcium uptake. Researchers from IBCh RAS and Columbia University analyzed the structure of the key TRPV domain – the ion conducting pore. Using the original “dynamic molecular portrait” approach, they identified three major states of the pore that are common for all TRPVs, called α-closed, π-closed, and π-open. It was shown that the α-closed state is the most hydrophobic and always nonconducting. While the π-closed one is less stable and can easily transit to the open state, which has favorable hydrophobic properties for the ion conduction. The results were published in Communications Chemistry.

• Immune system regulation for nanoparticle drug delivery. Breaking the endless cycle in nanomedicine June 14, 2024

  The journey of discovery in scientific research sometimes follows a familiar path: discover, admire, investigate, disappoint, and forget. Nevertheless, in some disciplines, it seems repeating many times. One of such cycles in the field of immune system blockade by nanoparticles is analysed in a recent article published in Nature Communications journal. Scientists from the Institute of Bioorganic Chemistry, Uppsala University and Boston University propose that advancements in nanomaterial development may finally disrupt this cycle, potentially introducing the method of macrophage blockade into clinical practice to improve cancer therapy.

• Loss of Ability to regenerate Limbs in Higher Vertebrates: From Side Effects of Evolutionary Innovations to Gene Loss June 5, 2024

  Researchers from the Laboratory of Molecular Foundations of Embryogenesis at the GNC IBCh RAS have identified the main factors that rendered limb regeneration impossible in modern amniotes (reptiles, birds, and mammals). The authors suggested that after the ancestors of amniotes transitioned to land, their ability to regenerate limbs was suppressed by the side effects of various innovations that emerged at that time, which were necessary for successful colonization of land. This, in turn, stimulated the disappearance of many genes that ceased to participate in regeneration from that moment on. As a result, in modern amniotes, including humans, the inability to regenerate limbs became firmly fixed at the genomic level.