Macromolecular mimicry in protein biosynthesis

Elongation factor Tu (EF-Tu) is a G-protein which, in its active GTP conformation, protects and carries aminoacylated tRNAs (aa-tRNAs) to the ribosome during protein biosynthesis. EF-Tu consists of three structural domains of which the N-terminal domain consists of two special regions (switch I and switch II) which are structurally dependent on the type of the bound nucleotide. Structural studies of the complete functional cycle of EF-Tu reveal that it undergoes rather spectacular conformational changes when activated from the EF-Tu·GDP form to the EF-Tu·GTP form. In its active form, EF-Tu·GTP without much further structural change interacts with aa-tRNAs in the so-called ternary complex. The conformational changes of EF-Tu involve rearrangements of the secondary structures of both the switch I and switch II regions. As the switch II region forms part of the interface between domains 1 and 3, its structural rearrangement results in a very large change of the position of domain 1 relative to domains 2 and 3. The overall shape of the ternary complex is surprisingly similar to the overall shape of elongation factor G (EF-G). Thus, three domains of the protein EF-G seem to mimic the tRNA part of the ternary complex. This macromolecular mimicry has profound implications for the function of the elongation factors on the ribosome

The possibility of using Ig Y-antibodies in immunotherapy

The importance of yolk antibodies (IgY) for their use in the diagnosis and treatment of human diseases is shown. The structural features of IgY compared to human immunoglobulins were studied. The disadvantages of obtaining hyperimmune sera from mammalian animals were revealed. A feature of IgY is its resistance to trypsin and chymotrypsin, which can contribute to more effective treatment of diseases. Data on optimization of the technology for obtaining yolk antibodies (IgY) from various bird species are presented. It is shown that 25-50 mg of highly purified immunoglobulin can be obtained from one bird egg. Obtaining immunoglobulins from eggs is more humane than using mammals for this purpose. Compared to ion exchange chromatography, gel chromatography, and ultrafiltration, the methods of precipitation with various chemicals (ammonium sulfate) were found to be simpler in terms of methodology. The results of electrophoresis revealed two types of proteins with a molecular weight of about 65 kDa and 30 kDa, which corresponds to the mass of the «heavy» and «light» IgY chains. Quail species Coturnix coturnix japonica as a producer of biological raw materials for the production of diagnostic immunoglobulins have great advantages over chickens (Gallus domesticus)

Inflammasome Activation Induces Pyroptosis in the Retina Exposed to Ocular Hypertension Injury

Mechanical stress and hypoxia during episodes of ocular hypertension (OHT) trigger glial activation and neuroinflammation in the retina. Glial activation and release of pro-inflammatory cytokines TNFα and IL-1β, complement, and other danger factors was shown to facilitate injury and loss of retinal ganglion cells (RGCs) that send visual information to the brain. However, cellular events linking neuroinflammation and neurotoxicity remain poorly characterized. Several pro-inflammatory and danger signaling pathways, including P2X7 receptors and Pannexin1 (Panx1) channels, are known to activate inflammasome caspases that proteolytically activate gasdermin D channel-formation to export IL-1 cytokines and/or induce pyroptosis. In this work, we used molecular and genetic approaches to map and characterize inflammasome complexes and detect pyroptosis in the OHT-injured retina. Acute activation of distinct inflammasome complexes containing NLRP1, NLRP3 and Aim2 sensor proteins was detected in RGCs, retinal astrocytes and Muller glia of the OHT-challenged retina. Inflammasome-mediated activation of caspases-1 and release of mature IL-1β were detected within 6 h and peaked at 12–24 h after OHT injury. These coincided with the induction of pyroptotic pore protein gasdermin D in neurons and glia in the ganglion cell layer (GCL) and inner nuclear layer (INL). The OHT-induced release of cytokines and RGC death were significantly decreased in the retinas of Casp1−/−Casp4(11)del, Panx1−/− and in Wild-type (WT) mice treated with the Panx1 inhibitor probenecid. Our results showed a complex spatio-temporal pattern of innate immune responses in the retina. Furthermore, they indicate an active contribution of neuronal NLRP1/NLRP3 inflammasomes and the pro-pyroptotic gasdermin D pathway to pathophysiology of the OHT injury. These results support the feasibility of inflammasome modulation for neuroprotection in OHT-injured retinas

Smart cities in China: growth driver in the post pandemic world

Research background: In recent decades, a global trend towards the introduction of IoT technologies, artificial intelligence, blockchain, and many others into the field of urban management to create a single digital ecosystem has become increasingly noticeable. The urgency of this problem also manifested itself during the COVID-19 pandemic, and many components of the smart city made it possible to control and contain the spread of the infection. All these factors testify that in current conditions, the digitalization of cities is simply inevitable. In this regard, the number of smart cities continues to increase worldwide, and their development models are constantly improving under the influence of a considerable number of innovative solutions Purpose of the article: Of particular interest are the Chinese successes in the rapid digitalization of the economy and society and the increase in the number of smart cities. The study aims to analyze and identify trends in the development of smart cities in China. Methods: Since the concept of "smart city" is relatively modern and is in constant development, the authors have studied various articles and reports on this topic to identify different opinions about this topical problem. As part of the study, the authors carried out a visual clustering analysis of smart cities distribution in China. Findings & Value added: The authors were able to identify that the Chinese smart cities market has its own characteristic features, which allowed it to achieve such success. In more detail in this article, the authors focused on cluster development and highlighted the geographical pattern of smart cities distribution in China and their strengths and weaknesses in each area

The possibility of using Ig Y-antibodies in immunotherapy

The importance of yolk antibodies (IgY) for their use in the diagnosis and treatment of human diseases is shown. The structural features of IgY compared to human immunoglobulins were studied. The disadvantages of obtaining hyperimmune sera from mammalian animals were revealed. A feature of IgY is its resistance to trypsin and chymotrypsin, which can contribute to more effective treatment of diseases. Data on optimization of the technology for obtaining yolk antibodies (IgY) from various bird species are presented. It is shown that 25-50 mg of highly purified immunoglobulin can be obtained from one bird egg. Obtaining immunoglobulins from eggs is more humane than using mammals for this purpose. Compared to ion exchange chromatography, gel chromatography, and ultrafiltration, the methods of precipitation with various chemicals (ammonium sulfate) were found to be simpler in terms of methodology. The results of electrophoresis revealed two types of proteins with a molecular weight of about 65 kDa and 30 kDa, which corresponds to the mass of the «heavy» and «light» IgY chains. Quail species Coturnix coturnix japonica as a producer of biological raw materials for the production of diagnostic immunoglobulins have great advantages over chickens (Gallus domesticus)

The Inflammasome-Dependent Dysfunction and Death of Retinal Ganglion Cells after Repetitive Intraocular Pressure Spikes

The dysfunction and selective loss of retinal ganglion cells (RGCs) is a known cause of vision loss in glaucoma and other neuropathies, where ocular hypertension (OHT) is the major risk factor. We investigated the impact of transient non-ischemic OHT spikes (spOHT) on RGC function and viability in vivo to identify cellular pathways linking low-grade repetitive mechanical stress to RGC pathology. We found that repetitive spOHT had an unexpectedly high impact on intraocular homeostasis and RGC viability, while exposure to steady OHT (stOHT) of a similar intensity and duration failed to induce pathology. The repetitive spOHT induced the rapid activation of the inflammasome, marked by the upregulation of NLRP1, NLRP3, AIM2, caspases -1, -3/7, -8, and Gasdermin D (GSDMD), and the release of interleukin-1β (IL-1β) and other cytokines into the vitreous. Similar effects were also detected after 5 weeks of exposure to chronic OHT in an induced glaucoma model. The onset of these immune responses in both spOHT and glaucoma models preceded a 50% deficit in pattern electroretinogram (PERG) amplitude and a significant loss of RGCs 7 days post-injury. The inactivation of inflammasome complexes in Nlrp1−/−, Casp1−/−, and GsdmD−/− knockout animals significantly suppressed the spOHT-induced inflammatory response and protected RGCs. Our results demonstrate that mechanical stress produced by acute repetitive spOHT or chronic OHT is mechanistically linked to inflammasome activation, which leads to RGC dysfunction and death