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IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) is member of the IQGAP family of scaffold proteins, which are essential for assembling multiprotein complexes that coordinate various intracellular signaling pathways. Previous research has shown that IQGAP3 is overexpressed in psoriatic skin lesions. Given its involvement in processes like cell proliferation and chemokine signaling, we sought to explore its molecular role in driving the psoriatic phenotype of keratinocytes. By conducting transcriptome profiling of HaCaT keratinocytes, we identified numerous psoriasis-associated pathways that were affected when IQGAP3 was knocked down. These included alterations in NFkB signaling, EGFR signaling, activation of p38/MAPK and ERK1/ERK2, lipid metabolism, cytokine production, and the response to inflammatory cytokine stimulation. Real-time analysis further revealed changes in cell growth dynamics, including proliferation and wound healing. The balance between cell proliferation and apoptosis was altered, as were skin barrier functions and the production of IL-6 and IFNγ. Despite these significant findings, the diversity of the alterations observed in the knockdown cells led us to conclude that IQGAP3 may not be the best target for the therapeutic inhibition to normalize the phenotype of keratinocytes in psoriasis.

The main quality attributes of radiopharmaceuticals that ensure their effectiveness and safety and are unique to their specifications are activity, radionuclide identity, radionuclide purity, and radiochemical purity. The aim of this study was to analyse the possibility of formation and methods for determination of various impurities in radiopharmaceuticals based on radionuclides of several groups: technetium-99m and rhenium-188; iodine and fluorine-18 isotopes; and gallium-68 and some other metallic radionuclides used in theranostic schemes combining radionuclide diagnostics and radionuclide therapy. The article analyses the sources for the formation of radionuclide, radiochemical, and chemical impurities; the influence of these impurities on visualisation quality and dosimetric characteristics of radiopharmaceuticals; various approaches to the methods of impurity detection and quantification; compendial requirements to the quality of radiopharmaceuticals; and research results reported in publications. The article demonstrates the need for the development and certification of Russian reference standards for testing quality attributes of radiopharmaceuticals as part of harmonisation of the State Pharmacopoeia of the Russian Federation with the Pharmacopoeia of the Eurasian Economic Union and the European Pharmacopoeia.

In previous work, we experimentally demonstrated the possibility of using RNA aptamers to inhibit endogenous protein expression and their function within plant cells In the current work, we show that our proposed method is suitable for inhibiting the functions of exogenous, foreign proteins delivered into the plant via various mechanisms, including pathogen proteins. Stringent experimentation produced robust RNA aptamers that are able to bind to the recombinant HopU1 effector protein of P. syringae bacteria. This research uses genetic engineering methods to constitutively express/transcribe HopU1 RNA aptamers in transgenic A. thaliana. Our findings support the hypothesis that HopU1 aptamers can actively interfere with the function of the HopU1 protein and thereby increase resistance to phytopathogens of the genus P. syringae pv. tomato DC 3000.

Background and aim Human evolution resulted from changes in our biology, behaviour, and culture. One source of these changes has been hypothesised to be our self-domestication (that is, the development in humans of features commonly found in domesticated strains of mammals, seemingly as a result of selection for reduced aggression). Signals of domestication, notably brain size reduction, have increased in recent times. Methods In this paper, we compare whole-genome data between the Late Neolithic/Bronze Age individuals and modern Europeans. Results We show that genes associated with mammal domestication and with neural crest development and function are significantly differently enriched in nonsynonymous single nucleotide polymorphisms between these two groups. Conclusion We hypothesise that these changes might account for the increased features of self-domestication in modern humans and, ultimately, for subtle recent changes in human cognition and behaviour, including language.

Introduction. Skin cancers came first in Russia in numbers of oncological diseases. Melanoma, making up only a small part of these cases, leads to the most serious consequences. The nuclear medicine methods application is necessary at the stages of clarifying the diagnosis, searching for remote metastases and the treatment monitoring. The work is devoted to one of the stages of the radiopharmaceutical development for the diagnostics of malignant melanoma and its metastases based on the synthetic analog of α-melanocyte stimulating hormone (SAH) and radionuclide Tc-99m.Aim. The selection of optimal conditions for the preparation of the SAH ∙ 99mTc complex and the study of the using possibility it as a diagnostic tool in in vitro experiments.Materials and methods. Experimental work was carried out to optimize the conditions for obtaining the complex compound SAH ∙ 99mTc. The binding and internalization of this compound by B16-F0 melanoma cells has been studied.Results and discussion. The results of labeling SAH with a 99mTc radionuclide under a wide range of conditions were obtained both by the direct method and using the intermediate complex. The target compound rapidly binds to B16-F0 melanoma cells. The degree of internalization is more than 85 %.Conclusion. Based on the results of chemical experiments and data from in vitro experiments, optimal conditions for obtaining a complex compound SAH ∙ 99mTc with a radiochemical yield of more than 90 % were found. The mechanism of binding of this compound to malignant melanoma cells has been established.

Introduction. The early detection of tumor growth remains one of the most important tasks of diagnostic nuclear medicine. The vascular growth being created malignant neoplasms is a good target for the purpose. The molecular participants in the process are gallium-68 labeled vector to the delivery of radionuclides and positron-emission tomography (PET) imaging.Aim. Possibility researching of using the complex gallium-68 labeled peptide sequence RGD for PET imaging of tumor with different grade of neovascularization.Materials and methods. Complex compound of Ga-68 with the peptide NODAGA-cRGD2 (the proposed name used below is «Vascular, 68Ga») was used for studying of the distribution in mice with transplanted heterotopic xenografts of glioblastoma U-87 MG and breast adenocarcinoma Ca-755 after intravenous injection, as well as the possibility of visualization the tumor.Results and discussion. The «Vascular, 68Ga» biodistribution in the mice body is usual of laboratory animals is usual of the behavior of peptides in vivo: rapid clearance from the blood, intense urinary excretion. The accumulation of the drug in the area of glioblastoma in mice is on average 2 times higher than that in adenocarcinoma. The results of in vivo PET imaging of experimental tumor lesions correlate well with ex vivo radiometry data. Conclusion. The «Vascular, 68Ga» actively accumulated in well-vascularized tumor foci after intravenous injection and rapidly excreted from the body through the kidneys without noticeable non-specific accumulation in other organs and tissues. The PET imaging possibility of experimental tumor foci was shown.

Mycelial fungi grow as colonies consisting of polar growing hyphae, developing radially from spore or inoculum. Over time, the colony develops, hyphae are subject to various exogenous or endogenous stimuli, and mycelium becomes heterogeneous in growth, gene expression, biosynthesis, and secretion of proteins and metabolites. Although the biochemical and molecular mechanisms of mycelium heterogeneity have been the subject of many studies, the role of lipids in colony development and zonality is still not understood. This work was undertaken to extend our knowledge of mycelium heterogeneity and to answer the question of how different lipid molecular species are distributed in the surface colony of the basidial fungus Flammulina velutipes and how this distribution correlates with its morphology. The heterogeneity in the lipid metabolism and lipid composition of the fungal mycelium was demonstrated. According to the real-time PCR and LC-MS/MS results, the expression of genes of PC metabolism, accumulation of phospholipid classes, and degree of unsaturation of PC and PE increased in the direction from the center to the periphery of the colony. The peripheral zone of the colony was characterized by a higher value of the PC/PE ratio and a higher level of phospholipids esterified by linolenic acid. Considering that the synthesis of phospholipids in fungi occurs in different ways, we also conducted experiments with deuterium-labeled phospholipid precursors and found out that the Kennedy pathway is the predominant route for PC biosynthesis in F. velutipes. The zonal differences in gene expression and lipid composition can be explained by the participation of membrane lipids in polar growth maintenance and regulation.

IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) is member of the IQGAP family of scaffold proteins, which are essential for assembling multiprotein complexes that coordinate various intracellular signaling pathways. Previous research has shown that IQGAP3 is overexpressed in psoriatic skin lesions. Given its involvement in processes like cell proliferation and chemokine signaling, we sought to explore its molecular role in driving the psoriatic phenotype of keratinocytes. By conducting transcriptome profiling of HaCaT keratinocytes, we identified numerous psoriasis-associated pathways that were affected when IQGAP3 was knocked down. These included alterations in NFkB signaling, EGFR signaling, activation of p38/MAPK and ERK1/ERK2, lipid metabolism, cytokine production, and the response to inflammatory cytokine stimulation. Real-time analysis further revealed changes in cell growth dynamics, including proliferation and wound healing. The balance between cell proliferation and apoptosis was altered, as were skin barrier functions and the production of IL-6 and IFNγ. Despite these significant findings, the diversity of the alterations observed in the knockdown cells led us to conclude that IQGAP3 may not be the best target for the therapeutic inhibition to normalize the phenotype of keratinocytes in psoriasis. [ABSTRACT FROM AUTHOR]

Triosephosphate isomerase (TPI) deficiency (Df) is a rare recessive metabolic disorder that manifests as hemolytic anemia, locomotor impairment, and progressive neurodegeneration. Research suggests that TPI Df mutations, including the “common” TPIE105Dmutation, result in reduced TPI protein stability that appears to underlie disease pathogenesis. Drosophila with the recessive TPIsugarkill allele (a.k.a. sgk or M81T) exhibit progressive locomotor impairment, neuromuscular impairment and reduced longevity, modeling the human disorder. TPIsugarkill produces a functional protein that is degraded by the proteasome. Molecular chaperones, such as Hsp70 and Hsp90, have been shown to contribute to the regulation of TPIsugarkill degradation. In addition, stabilizing the mutant protein through chaperone modulation results in improved TPI deficiency phenotypes. To identify additional regulators of TPIsugarkill degradation, we performed a genome-wide RNAi screen that targeted known and predicted quality control proteins in the cell to identify novel factors that modulate TPIsugarkill turnover. Of the 430 proteins screened, 25 regulators of TPIsugarkill were identified. Interestingly, 10 proteins identified were novel, previously undescribed Drosophila proteins. Proteins involved in co-translational protein quality control and ribosome function were also isolated in the screen, suggesting that TPIsugarkill may undergo co-translational selection for polyubiquitination and proteasomal degradation as a nascent polypeptide. The proteins identified in this study may reveal novel pathways for the degradation of a functional, cytosolic protein by the ubiquitin proteasome system and define therapeutic pathways for TPI Df and other biomedically important diseases.

Transcription factors (TFs) play a central role in the gene regulation associated with a plant's development and its response to the environmental factors. The work of TFs is well regulated at each stage of their activities. TFs usually consist of three protein domains required for DNA binding, dimerization, and transcriptional regulation. Alternative splicing (AS) produces multiple proteins with varying composition of domains. Recent studies have shown that AS of some TF genes form small proteins (small interfering peptide/small interfering protein, siPEP/siPRoT), which lack one or more domains and negatively regulate target TFs by the mechanism of protein interference (peptide interference/protein interference, PEPi/PROTi). The presence of an alternative form for the transcription factor CCA1 of Arabidopsis thaliana, has been shown to be involved in the regulation of the response to cold stress. For the PtFLC protein, one of the isoforms was found, which is formed as a result of alternative splicing and acts as a negative repressor, binding to the full-length TF PtFLC and therefore regulating the development of the Poncirus trifoliata. For A. thaliana, a FLM gene was found forming the FLM-б isoform, which acts as a dominant negative regulator and stimulates the development of the flower formation process due to the formation of a heterodimer with SVP TF. Small interfering peptides and proteins can actively participate in the regulation of gene expression, for example, in situations of stress or at different stages of plant development. Moreover, small interfering peptides and proteins can be used as a tool for fundamental research on the function of genes as well as for applied research for permanent or temporary knockout of genes. In this review, we have demonstrated recent studies related to siPEP/siPROT and their involvement in the response to various stresses, as well as possible ways to obtain small proteins.

Matrix metalloproteinases (MMPs) are important for the pathogenesis of psoriasis and other autoimmune disorders. In the extracellular matrix, accumulation of proinflammatory cytokines, such as interleukin 17A (IL-17A), leads to induction of several MMPs, including MMP1. MMPs change the composition and other properties of the extracellular matrix. These changes facilitate tissue remodeling and promote the development of psoriatic plaques. The aim of this study was to explore how MMP1 silencing might influence the biological effects of IL-17A on migration and proliferation of human epidermal keratinocytes and the expression of genes involved in their division and differentiation. The experiments were performed with MMP1-deficient and control epidermal keratinocytes, HaCaT-MMP1 and HaCaT-KTR, respectively. Cell proliferation and migration were assessed by comparative analysis of the growth curves and scratch assay, respectively. To quantify cell migration, representative areas of cell cultures were photographed at the indicated time points and compared to each other. Changes in gene expression were analyzed by real-time PCR. The obtained results demonstrated that MMP1 silencing in the cells treated with IL-17A resulted in downregulation of MMP9 and -12, FOSL1, CCNA2, IVL, KRT14 and -17 as well as upregulation of MMP2, CCND1 and LOR. Moreover, MMP1 silencing led to a decrease in cell proliferation and an impairment of cell migration. Thus, MMP1-deficiency in epidermal keratinocytes can be beneficial for psoriasis patients that experience an accumulation of IL-17 in lesional skin. Knocking MMP1 down could influence migration and proliferation of epidermal keratinocytes in vivo, as well as help to control the expression of MMP1, -2, -9 и -12, CCNA2, CCND1, KRT14 and -17 that are crucial for the pathogenesis of psoriasis.

The article discusses promising approaches to creating a digital corporation by using methods and technologies of predicting analytical research and describes principles of transforming the existing company information systems into digital systems of corporate governance. The author analyzed key technological trends of global digitalization and international research connected with them. The author puts forward a new information model of digital corporation, which in contrast to the present day analogues provides support to operational managerial decision-making in real time. He shows the role and place of forecasting modeling in raising operational efficiency of the trade company and potential results of introducing the digital system of governance.

Fractures in ankylosing spondylitis (AS) are often difficult to treat and surgical treatment may be fraught with complications. We describe the use of a robotic-assisted device in the surgical treatment of an unstable L1 fracture in an elderly patient with chronic lymphocytic leukemia and AS. The postoperative course was uneventful and the patient was discharged after 3 days. The use of a robotic-assisted device in spine surgery is particularly indicated in difficult high risk cases.

The involvement of plant immunophilins in multiple essential processes such as development, various ways of adapting to biotic and abiotic stresses, and photosynthesis has already been established. Previously, research has demonstrated the involvement of three immunophilin genes (AtCYP19-1/ROC3, AtFKBP65/ROF2, and AtCYP57) in the control of plant response to invasion by various pathogens. Current research attempts to identify host target proteins for each of the selected immunophilins. As a result, candidate interactors have been determined and confirmed using a yeast 2-hybrid (Y2H) system for protein–protein interaction assays. The generation of mutant isoforms of ROC3 and AtCYP57 harboring substituted amino acids in the in silico-predicted active sites became essential to achieving significant binding to its target partners. This data shows that ROF2 targets calcium-dependent lipid-binding domain-containing protein (At1g70790; AT1) and putative protein phosphatase (At2g30020; АТ2), whereas ROC3 interacts with GTP-binding protein (At1g30580; ENGD-1) and RmlC-like cupin (At5g39120). The immunophilin AtCYP57 binds to putative pyruvate decarboxylase-1 (Pdc1) and clathrin adaptor complex-related protein (At5g05010). Identified interactors confirm our previous findings that immunophilins ROC3, ROF2, and AtCYP57 are directly involved with stress response control. Further, these findings extend our understanding of the molecular functional pathways of these immunophilins.