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OFDM in radar systems gives as an opportunity to generate all desired signals. It can overcome the problem of ambiguity function for distance and velocity of target, has an ability to detect multiple targets simultaneously and insert identification (IFF) bits for distinguish enemy targets. [ABSTRACT FROM AUTHOR]

Digital beamforming allows to analyze the all beams simultaneously. The implementation of digital signal processing for this challenge we used the FPGA, because the FPGAs can proceed parallel processing. We have created the 8 beams and 3 modes for 3D OFDM Radar. The mode names are Normal, Offset and Mono, which are used for different Radar applications. For DBF (Digital Beam Formation) we have used 4 antennas and each of that has 5 rectangular patch elements. The type of feeding for these antennas is serial. To achieve better side lobe level the rectangular patch sizes are modified by Dolph-Chebishev function. The receiver antenna array beamwidth in azimuth plane is 25° and in elevation plane is 60°. [ABSTRACT FROM AUTHOR]

Immune complexes are important mediators of the inflammation that play a decisive role inpathogenesis of stroke and familial Mediterranean fever. Our previous studies have demonstrated elevated levels of immune complexes in the conditions of acute inflammation including ischemic stroke, hemorrhagic stroke and familial Mediterranean fever. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (in both reduced and non-reduced conditions) of the IC isolated from the blood of the affected subjects demonstrated the presence of protein with apparent molecular weight of 19kDa, which was not detected in the IC isolated from the blood of healthy subjects. In the present study we isolated this protein from the IC of patients with IS, HS and FMF, determined its N-terminal amino acid sequence for the first 12 residues, identified its nature using protein database, and finally provided evidence that it each diseased condition it represents a subunit of C-reactive protein. We propose that increased level CRP in circulation in the conditions of acute inflammation may lead to a generation of anti-CRP autoantibodies result in further immobilization of C-reactive protein in the immune complexes. [ABSTRACT FROM AUTHOR]

Familial Mediterranean Fever (FMF) is a genetic disorder with complex inheritance patterns and genotype-phenotype associations, and it is highly prevalent in Armenia. FMF typically follows an autosomal recessive inheritance pattern (OMIM: 249100), though it can occasionally display a rare dominant inheritance pattern with variable penetrance (OMIM։134610). The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein. While the 26 most prevalent mutations account for nearly 99% of all FMF cases, more than 60 pathogenic mutations have been identified. In this study, we aimed to develop an affordable nanopore sequencing method for full-length MEFV gene mutation detection to aid in the diagnosis and screening of FMF. We employed a multiplex amplicon sequencing approach, allowing for the processing of up to 12 samples on both Flow cells and Flongle flow cells. The results demonstrated near-complete concordance between nanopore variant calling and qPCR genotypes. Moreover, nanopore sequencing identified additional variants, which were confirmed by whole exome sequencing. Additionally, intronic and UTR variants were detected. Our findings demonstrate the feasibility of full-gene nanopore sequencing for detecting FMF-associated pathogenic variants. The method is cost-effective, with costs comparable to those of the qPCR test, making it particularly suitable for settings with limited laboratory infrastructure. Further clinical validation using larger sample cohorts will be necessary., Competing Interests: Author AD was employed by “Gisane” LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ghukasyan, Khachatryan, Sirunyan, Minasyan, Hakobyan, Chavushyan, Hayrapetyan, Ghazaryan, Martirosyan, Mkrtchyan, Vardanyan, Mukuchyan, Davidyants, Zakharyan and Arakelyan.)

The molecular events underlying the development, manifestation, and course of schizophrenia, bipolar disorder, and major depressive disorder span from embryonic life to advanced age. However, little is known about the early dynamics of gene expression in these disorders due to their relatively late manifestation. To address this, we conducted a secondary analysis of post-mortem prefrontal cortex datasets using bioinformatics and machine learning techniques to identify differentially expressed gene modules associated with aging and the diseases, determine their time-perturbation points, and assess enrichment with expression quantitative trait loci (eQTL) genes. Our findings revealed early, mid, and late deregulation of expression of functional gene modules involved in neurodevelopment, plasticity, homeostasis, and immune response. This supports the hypothesis that multiple hits throughout life contribute to disease manifestation rather than a single early-life event. Moreover, the time-perturbed functional gene modules were associated with genetic loci affecting gene expression, highlighting the role of genetic factors in gene expression dynamics and the development of disease phenotypes. Our findings emphasize the importance of investigating time-dependent perturbations in gene expression before the age of onset in elucidating the molecular mechanisms of psychiatric disorders., (© 2024. The Author(s).)

The CONSTANS ( CO ) gene in Arabidopsis thaliana has a central role in photoperiodic regulation of flowering. However, the roles of CO genes in mediating flowering in soybeans ( Glycine max ) remain uncertain. We previously inferred regulatory interactions of a soybean CO homolog, GmCOL1b , using in-house RNA-seq data and the network inference algorithm package CausNet. Here, we identify potential GmCOL1b downstream genes and experimentally verify them by expressing GmCOL1b in soybean protoplast cells. Temporal expression patterns of these genes indicate the regulatory effects of GmCOL1b on the expression of the circadian clock genes GmLCL1 and GmLCL4 and the flowering regulator GmTEM1a ., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

With progressing climate fluctuations, an understanding of the molecular mechanisms of crop plants that regulate their flowering responses to environments is crucial. To achieve this goal, we aimed at clarifying the gene regulatory networks among the circadian clock and flowering genes in soybean ( Glycine max ). Based on our network inference approach , we hypothesize that GmELF3-1 , one of the Evening Complex (EC) gene homologs in soybean's circadian clock, may have an integrative role in transcriptional regulation of the circadian clock and flowering gene network. In this study, we verify GmELF3-1 ' s regulatory roles in its potential downstream genes by modulating the activity of GmELF3-1 using overexpression and CRISPR-Cas9 in soybean protoplasts. Our results indicate that GmELF3-1 may control the expression of the PRR genes in the circadian clock and the flowering gene GmCOL1a ., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

Objectives: The objective of this study was to perform a comparative analysis of allelic diversity to reveal population-genetic characteristics of animal breeds, namely Shami (SH), Holstein (HLS), and Aberdeen-Angus (A-A)., Materials and Methods: The genetic materials of SH breed animals represented by wool with hair follicles were collected from 39 SH heads in Syria. Also, genetic materials of HLS breed of American selection ( n = 55, HLS) and bulls and cows of A-A breed bred at breeding enterprises in Russia ( n = 30, A-A) were collected. Genetic differences between the cattle groups were studied using 11 microsatellite markers., Results: The cattle breed in Syria was characterized by high genetic diversity, 107 alleles, while the average number of alleles per microsatellite locus was 9.23, which is significantly higher than that in the animals of HLS (6.18) and A-A (5.00). When analyzing the genetic equilibrium for individual locus in SH breed, a deviation from equilibrium at four loci was revealed: TGLA227, SPS115, TGLA122, and ETH225; at one locus in HLS breed: SPS115, for A-A breed: at two loci, i.e., TGLA122 and ETH225. When assessing the level of genetic consolidation, a deficiency of heterozygotes was observed in two of the three studied breeds: 4.8% for SH and 8.0% for A-A. A slight excess of heterozygotes was found in the HLS breed at the level of 0.2%. The average comparative measurement of genetic variation in different populations value for 11 loci for all breeds was 0.069, which indicates that 93.1% of the total variability is due to the intra-breed diversity, and only 6.9% is due to the differences between breeds., Conclusion: The analysis of the animals belonging to their breed has shown a 100% genetic consolidation and the compliance of individual animals with the respective breeds. The study of genetic distances, adjusted for small samples, revealed the smallest genetic distance between the SH breed and HLS breed, equaling 0.107. The A-A breed, which has its separate origin and has never been imported into the Syrian Arab Republic, adjoins this cluster as an independent branch. Microsatellites can be used as an essential criterion for assessing the population-genetic characteristics of groups of cattle of various breeds (degree of polymorphism, level of heterozygosity, fixation indices, genetic group membership)., Competing Interests: None of the authors have any conflict of interest to declare., (Copyright: © Journal of Advanced Veterinary and Animal Research.)

Our study aims at developing knowledge-based strategies minimizing chronic changes in the brain after severe spinal cord injury (SCI). The SCI-induced long-term metabolic alterations and their reactivity to treatments shortly after the injury are characterized in rats. Eight weeks after severe SCI, significant mitochondrial lesions outside the injured area are demonstrated in the spinal cord and cerebral cortex. Among the six tested enzymes essential for the TCA cycle and amino acid metabolism, mitochondrial 2-oxoglutarate dehydrogenase complex (OGDHC) is the most affected one. SCI downregulates this complex by 90% in the spinal cord and 30% in the cerebral cortex. This is associated with the tissue-specific changes in other enzymes of the OGDHC network. Single administrations of a pro-activator (thiamine, or vitamin B1, 1.2 mmol/kg) or a synthetic pro-inhibitor (triethyl glutaryl phosphonate, TEGP, 0.02 mmol/kg) of OGDHC within 15-20 h after SCI are tested as protective strategies. The biochemical and physiological assessments 8 weeks after SCI reveal that thiamine, but not TEGP, alleviates the SCI-induced perturbations in the rat brain metabolism, accompanied by the decreased expression of (acetyl)p53, increased expression of sirtuin 5 and an 18% improvement in the locomotor recovery. Treatment of the non-operated rats with the OGDHC pro-inhibitor TEGP increases the p53 acetylation in the brain, approaching the brain metabolic profiles to those after SCI. Our data testify to an important contribution of the OGDHC regulation to the chronic consequences of SCI and their control by p53 and sirtuin 5., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boyko, Tsepkova, Aleshin, Artiukhov, Mkrtchyan, Ksenofontov, Baratova, Ryabov, Graf and Bunik.)

Thiamine (vitamin B1) is a precursor of the well-known coenzyme of central metabolic pathways thiamine diphosphate (ThDP). Highly intense glucose oxidation in the brain requires ThDP-dependent enzymes, which determines the critical significance of thiamine for neuronal functions. However, thiamine can also act through the non-coenzyme mechanisms. The well-known facilitation of acetylcholinergic neurotransmission upon the thiamine and acetylcholine co-release into the synaptic cleft has been supported by the discovery of thiamine triphosphate (ThTP)-dependent phosphorylation of the acetylcholine receptor-associated protein rapsyn, and thiamine interaction with the TAS2R1 receptor, resulting in the activation of synaptic ion currents. The non-coenzyme regulatory binding of thiamine compounds has been demonstrated for the transcriptional regulator p53, poly(ADP-ribose) polymerase, prion protein PRNP, and a number of key metabolic enzymes that do not use ThDP as a coenzyme. The accumulated data indicate that the molecular mechanisms of the neurotropic action of thiamine are far broader than it has been originally believed, and closely linked to the metabolism of thiamine and its derivatives in animals. The significance of this topic has been illustrated by the recently established competition between thiamine and the antidiabetic drug metformin for common transporters, which can be the reason for the thiamine deficiency underlying metformin side effects. Here, we also discuss the medical implications of the research on thiamine, including the role of thiaminases in thiamine reutilization and biosynthesis of thiamine antagonists; molecular mechanisms of action of natural and synthetic thiamine antagonists, and biotransformation of pharmacological forms of thiamine. Given the wide medical application of thiamine and its synthetic forms, these aspects are of high importance for medicine and pharmacology, including the therapy of neurodegenerative diseases.

There is significant evidence that pathology of the microcirculation occurs in African swine fever (ASF); however, the mechanisms by which it develops are largely unknown. In the present experimental infection study, we show that an increase in vascular permeability in the initial stages of acute ASF is dependent on viraemia and elevation of the concentration of serum nitric oxide (NO). Macrophages activated by ASF virus (ASFV) are stimulated to produce NO and simultaneously to sensitize the endothelial cells through the action of vascular endothelial growth factor Β (VEGFΒ), which is followed by an increase in VEGF-mediated endothelial permeability. In the later stages of disease, the endothelial cells undergo DNA proliferation, which may additionally provoke capillary leakage, point haemorrhages and migration of blood cells into tissues. The possible mechanism of a shift in the cell cycle from the G1 to S and G2 stages could be a direct effect of ASFV. The terminal stages of disease are characterized by triggering of compensatory mechanisms such as stimulation of the synthesis of stromal cell-derived factor-1., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Human exonuclease 1 (EXO1), a 5'→3' exonuclease, contributes to the regulation of the cell cycle checkpoints, replication fork maintenance, and post replicative DNA repair pathways. These processes are required for the resolution of stalled or blocked DNA replication that can lead to replication stress and potential collapse of the replication fork. Failure to restart the DNA replication process can result in double-strand breaks, cell-cycle arrest, cell death, or cellular transformation. In this review, we summarize the involvement of EXO1 in the replication, DNA repair pathways, cell cycle checkpoints, and the link between EXO1 and cancer.

An optimized method for analysis of free amino acids using a modified lithium-citrate buffer system with a Hitachi L-8800 amino acid analyzer is described. It demonstrates clear advantages over the sodium-citrate buffer system commonly used for the analysis of protein hydrolysates. A sample pretreatment technique for amino acid analysis of brain extracts is also discussed. The focus has been placed on the possibility of quantitative determination of the reduced form of glutathione (GSH) with simultaneous analysis of all other amino acids in brain extracts. The method was validated and calibration coefficient (K GSH ) was determined. Examples of chromatographic separation of free amino acids in extracts derived from different parts of the brain are presented.

Haemoglobin (Hb)-based oxygen carriers are under consideration as oxygen therapeutics. Their effect on apoptosis is critical, because the onset of pro-apoptotic pathways may lead to tissue damage. MP4OX, a polyethylene glycol-conjugated human Hb preserves the baseline level of neuron apoptosis with respect to sham. Here we develop a method for measuring Hb extravasation in brain. We exchange transfused rats by haemorrhaging 50% of their blood with simultaneous, isovolemic replacement with Hextend (negative control), MP4OX, or αα-cross-linked Hb. Animals were sacrificed 2 h after transfusion, brain tissue was harvested and processed for double-staining immunofluorescence, whereby Hb ? chain and NeuN (a neuron protein) were stained and quantitated. Whereas Hextend did not induce Hb extravasation, in both MP4OX and ??Hb brains Hb molecules were detected outside neurons. The level of extravasated Hb chains was > 3-fold higher in Hb compared to MP4OX. Western blot analysis revealed that the expression levels of protein related to redox imbalance (e.g., Nrf2, iNOS and ERK phosphorylation) were higher in ααHb than MP4OX. In conclusions, higher Hb extravasation in ααHb than MP4OX induces redox imbalance, which causes higher anti-oxidant response. Whereas Nrf2 response may be considered protective, iNOS response appears damaging.

Glutamate dehydrogenase (GDH) of animal cells is usually considered to be a mitochondrial enzyme. However, this enzyme has recently been reported to be also present in nucleus, endoplasmic reticulum and lysosomes. These extramitochondrial localizations are associated with moonlighting functions of GDH, which include acting as a serine protease or an ATP-dependent tubulin-binding protein. Here, we review the published data on kinetics and localization of multiple forms of animal GDH taking into account the splice variants, post-translational modifications and GDH isoenzymes, found in humans and apes. The kinetic properties of human GLUD1 and GLUD2 isoenzymes are shown to be similar to those published for GDH1 and GDH2 from bovine brain. Increased functional diversity and specific regulation of GDH isoforms due to alternative splicing and post-translational modifications are also considered. In particular, these structural differences may affect the well-known regulation of GDH by nucleotides which is related to recent identification of thiamine derivatives as novel GDH modulators. The thiamine-dependent regulation of GDH is in good agreement with the fact that the non-coenzyme forms of thiamine, i.e., thiamine triphosphate and its adenylated form are generated in response to amino acid and carbon starvation., Competing Interests: The authors declare no conflict of interest.

2-Oxoglutarate dehydrogenase (OGDH) of the tricarboxylic acid (TCA) cycle is often implied to be inactive in cancer, but this was not experimentally tested. We addressed the question through specific inhibition of OGDH by succinyl phosphonate (SP). SP action on different cancer cells was investigated using indicators of cellular viability and reactive oxygen species (ROS), metabolic profiling and transcriptomics. Relative sensitivity of various cancer cells to SP changed with increasing SP exposure and could differ in the ATP- and NAD(P)H-based assays. Glioblastoma responses to SP revealed metabolic sub-types increasing or decreasing cellular ATP/NAD(P)H ratio under OGDH inhibition. Cancer cell homeostasis was perturbed also when viability indicators were SP-resistant, e.g. in U87 and N2A cells. The transcriptomics database analysis showed that the SP-sensitive cells, such as A549 and T98G, exhibit the lowest expression of OGDH compared to other TCA cycle enzymes, associated with higher expression of affiliated pathways utilizing 2-oxoglutarate. Metabolic profiling confirmed the dependence of cellular SP reactivity on cell-specific expression of the pathways. Thus, oxidative decarboxylation of 2-oxoglutarate is significant for the interdependent homeostasis of NAD(P)H, ATP, ROS and key metabolites in various cancer cells. Assessment of cell-specific responses to OGDH inhibition is of diagnostic value for anticancer strategies., Competing Interests: The authors declare no conflicts of interests.

Thiamin (vitamin B1) is a pharmacological agent boosting central metabolism through the action of the coenzyme thiamin diphosphate (ThDP). However, positive effects, including improved cognition, of high thiamin doses in neurodegeneration may be observed without increased ThDP or ThDP-dependent enzymes in brain. Here, we determine protein partners and metabolic pathways where thiamin acts beyond its coenzyme role. Malate dehydrogenase, glutamate dehydrogenase and pyridoxal kinase were identified as abundant proteins binding to thiamin- or thiazolium-modified sorbents. Kinetic studies, supported by structural analysis, revealed allosteric regulation of these proteins by thiamin and/or its derivatives. Thiamin triphosphate and adenylated thiamin triphosphate activate glutamate dehydrogenase. Thiamin and ThDP regulate malate dehydrogenase isoforms and pyridoxal kinase. Thiamin regulation of enzymes related to malate-aspartate shuttle may impact on malate/citrate exchange, responsible for exporting acetyl residues from mitochondria. Indeed, bioinformatic analyses found an association between thiamin- and thiazolium-binding proteins and the term acetylation. Our interdisciplinary study shows that thiamin is not only a coenzyme for acetyl-CoA production, but also an allosteric regulator of acetyl-CoA metabolism including regulatory acetylation of proteins and acetylcholine biosynthesis. Moreover, thiamin action in neurodegeneration may also involve neurodegeneration-related 14-3-3, DJ-1 and β-amyloid precursor proteins identified among the thiamin- and/or thiazolium-binding proteins.