Component Of Defense Research Articles

Physiological and Transcriptome Analysis Reveals the Differences in Genes of Antioxidative Defense Components and Cold-Related Proteins in Winter and Spring Wheat during Cold Acclimation

Recent findings suggest that cold acclimation can enhance cold resistance in wheat. Dongnongdongmai 1 (DM1) is a winter wheat variety that can overwinter at −30 °C; however, its cold acclimation mechanism is yet to be fully elucidated. Here, we elucidated the potential mechanisms of cold acclimation in DM1 and the China Spring (CS) variety, especially the role of the antioxidant system, using transcriptome and physiological analyses. Cold stress increased H2O2 and O2− production in both varieties; however, CS had higher contents of H2O2 and O2− than DM1. Moreover, cold significantly increased ROS-scavenging activities in DM1, especially at 30 days after exposure. Gene ontology (GO) analysis showed that differentially expressed peroxidase (POD) genes were enriched in antioxidant activity, with most POD genes being significantly upregulated in DM1 under cold acclimation. Additionally, cold acclimation increased the expression of cold acclimation protein (CAP), late embryogenesis abundant protein (LEA), and cold-responsive genes in both varieties, with higher expression levels in DM1. Overall, the results showed that DM1 exhibited a higher cold tolerance than CS during cold acclimation by increasing the expression of POD genes, LEA, CAP, and cold-responsive proteins, improving the understanding of the mechanism of cold resistance in DM1.

TNI MARITIME DIPLOMACY TO MAINTAIN REGIONAL SECURITY STABILITY IN THE FRAMEWORK OF MAINTAINING STATE SOVEREIGNTY

Indonesian maritime diplomacy is the implementation of foreign policy that is not only related to various maritime aspects at the bilateral, regional and global levels but also uses maritime assets, both civil and military to fulfill Indonesia's national interests in accordance with the provisions of national law and international law. The use of military assets in Indonesian maritime diplomacy is carried out by the Indonesian Navy as one of the main components of national defense which besides having duties in the field of defense and security at sea, also carries out naval diplomacy duties in order to support foreign policy policies set by the government. The objectives of this study are (1) to analyze the cooperative maritime diplomacy of the TNI in order to maintain regional security stability in order to maintain state sovereignty; (2) Analyzing the TNI's persuasive maritime diplomacy in order to maintain regional security stability in order to maintain state sovereignty; (3) Analyze the TNI's coercive maritime diplomacy in order to maintain regional security stability in order to maintain state sovereignty. This study used descriptive qualitative method. The results of this study are (1) The facilities and infrastructure that are owned are still limited, Pusinfomar TNI as the TNI's Balakpus Puspa which is still young is facing a long challenge to become a maritime security data center at the national and international level in supporting the TNI's cooperative maritime diplomacy tasks. Awareness of the importance of maritime information data has not grown nationally so that maritime data has not been properly managed between agencies and Ministries/Agencies and there has not been an exchange of information with regional countries in supporting the TNI's maritime diplomacy tasks through information exchange cooperation with domestic maritime data centers and regional countries Indo-Pacific; (2) The implementation of TNI's persuasive maritime diplomacy in the form of sea security training courses has not been carried out with all regional countries, especially with Vietnam and China, it is necessary to carry out training sessions with the two countries as a form of cooperative maritime diplomacy by using sea power assets in peacetime and building CBM in accordance with their respective national interests as well as to show Indonesia's role as the largest country and founder of ASEAN; (3) The bilateral and multilateral Patkor has not yet been fully implemented as a form of coercive maritime diplomacy between the TNI and neighboring countries in the face of the vastness of Indonesia's sea boundaries and the strategic bangling situation in the Indo-Pacific region, especially in the SCS region where ZEEI LNU borders with ZEE Vietnam and Malaysia

Protective Behaviors of Bio-Inspired Honeycomb Column Thin-Walled Structure against RC Slab under Impact Loading.

In order to protect the reinforced concrete (RC) slab structure from damage under some accidental conditions, such as impacting and explosion, we used bio-inspired honeycomb column thin-walled structure (BHTS) to serve as a buffer interlayer for the concrete structure inspired by the biological structure of beetle's elytra. The mechanical properties of AlSi10Mg used to fabricate the BHTS buffer interlayer were determined by low- and medium-speed uniaxial compression tests and numerical simulations. Subsequently, based on the drop weight impact test models, the effect of the buffer interlayer on the response of the RC slab under the drop weight tests with different energy input was compared by the impact force and duration, maximum displacement and residual displacement, energy absorption (EA), energy proportion, and other indicators. The results show that the proposed BHTS buffer interlayer has a very significant protection effect on the RC slab under the impact of the drop hammer. Due to its superior performance, the proposed BHTS buffer interlayer provides a promising solution for EA of augmented cellular structures widely used in defensive structural components, such as floor slabs, building walls, etc.

Arbuscular mycorrhizal fungus changes alfalfa response to pathogen infection activated by pea aphid infestation.

Arbuscular mycorrhizal (AM) fungi are important for the resistance of plants to insect infestation and diseases. However, the effect of AM fungal colonization of plants response to pathogen infection activated by pea aphid infestation is unknown. Pea aphid (Acyrthosiphon pisum) and the fungal pathogen Phoma medicaginis severely limit alfalfa production worldwide. This study established an alfalfa (Medicago sativa)-AM fungus (Rhizophagus intraradices)-pea aphid-P. medicaginis experimental system to clarify the effects of an AM fungus on the host plant response to insect infestation and subsequent fungal pathogen infection. Pea aphid increased the disease incidence of P. medicaginis by 24.94%. The AM fungus decreased the disease index by 22.37% and enhanced alfalfa growth by increasing the uptake of total nitrogen and total phosphorus. The aphid induced polyphenol oxidase activity of alfalfa, and the AM fungus enhanced plant-defense enzyme activity against aphid infestation and subsequent P. medicaginis infection. In addition, the AM fungus increased the contents of jasmonic acid and abscisic acid in plants exposed to aphid infestation or pathogen infection. Abscisic acid and genes associated with the gene ontology term "hormone binding" were upregulated in aphid-infested or pathogen-infected alfalfa. The results demonstrate that an AM fungus enhances plant defense and signaling components induced by aphid infestation, which may contribute to improved defense against subsequent pathogen infection.

Temperature modifies trait-mediated infection outcomes in a Daphnia-fungal parasite system.

One major concern related to climate change is that elevated temperatures will drive increases in parasite outbreaks. Increasing temperature is known to alter host traits and host-parasite interactions, but we know relatively little about how these are connected mechanistically-that is, about how warmer temperatures impact the relationship between epidemiologically relevant host traits and infection outcomes. Here, we used a zooplankton-fungus (Daphnia dentifera-Metschnikowia bicuspidata) disease system to experimentally investigate how temperature impacted physical barriers toinfection and cellular immune responses. We found that Daphnia reared at warmer temperatures had more robust physical barriers to infection but decreased cellular immune responses during the initial infection process. Infected hosts at warmer temperatures also suffered greater reductions infecundity andlifespan. Furthermore, the relationship between a key trait-gut epithelium thickness, a physical barrier-and the likelihood of terminal infection reversed at warmer temperatures. Together, our results highlight the complex waysthat temperatures can modulate host-parasite interactions and show that different defense components can have qualitatively different responses to warmer temperatures, highlighting the importance of considering key host traits when predicting disease dynamics in a warmer world. This article is part of the theme issue 'Infectious disease ecology and evolution in a changing world'.

Function and regulation of cGAS-STING signaling in infectious diseases.

The efficacious detection of pathogens and prompt induction of innate immune signaling serve as a crucial component of immune defense against infectious pathogens. Over the past decade, DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) and its downstream signaling adaptor stimulator of interferon genes (STING) have emerged as key mediators of type I interferon (IFN) and nuclear factor-κB (NF-κB) responses in health and infection diseases. Moreover, both cGAS-STING pathway and pathogens have developed delicate strategies to resist each other for their survival. The mechanistic and functional comprehension of the interplay between cGAS-STING pathway and pathogens is opening the way for the development and application of pharmacological agonists and antagonists in the treatment of infectious diseases. Here, we briefly review the current knowledge of DNA sensing through the cGAS-STING pathway, and emphatically highlight the potent undertaking of cGAS-STING signaling pathway in the host against infectious pathogenic organisms.

Selenium fortification stimulates antioxidant- and enzyme gene expression-related defense mechanisms in response to saline stress in Cucurbita pepo

Salinity dramatically decreases the yield of most agricultural plants by causing osmotic and ionic stress that negatively impacts plant growth and development. As previously documented, selenium (Se), as a serviceable trace element, alleviates abiotic stress impacts, particularly salinity, on several plant species. This work was done perfectly to evaluate the impact of leaf feeding with Se on indicators of salt tolerance in Cucurbita pepo. Salt stress (9.45 dS m−1) noticeably raised electrolyte leakage (EL) and malondialdehyde (MDA) owing to the rise in the examined markers of oxidative stress like hydrogen peroxide (H2O2) and superoxide (O2•‒), and Na+ content. As a result, the contents of osmo-regulators and non-enzymatic antioxidants, activities of enzymatic antioxidants, and enzyme gene expressions were markedly increased. The salinity-induced oxidative stress noticeably diminished growth features, membrane stability index (MSI), relative water content (RWC), K+/Na+ ratio, pigment, nutrient, and Se contents. Fruit yield and fruit content of Se and vitamin C also diminished. However, the application of Se noticeably decreased LI and MDA owing to the minimization in the levels of O2•‒, H2O2, and Na+. This positive outcome was connected with a further rise in the levels and activities of osmo-regulators, the defensive system components, and enzymatic gene expressions, which were positively reflected in the growth features, RWC, MSI, K+/Na+ ratio, pigment, nutrient, and Se contents, as well as fruit yield and fruit quality. Our results indicate that 15 g Se applied per hectare attenuated the negative impacts of salt stress in C. pepo via various mechanisms such as minimization of reactive oxygen species (ROS; O2•‒ and H2O2) and Na+ contents, and improvement of leaf integrity, nutrient homeostasis, photosynthetic capacity, osmoregulators and antioxidant enzyme activities, enzymatic gene expressions, and the regulation of Na+ homeostasis.

Apocrine secretion in the salivary glands of Drosophilidae and other dipterans is evolutionarily conserved.

Apocrine secretion is a transport and secretory mechanism that remains only partially characterized, even though it is evolutionarily conserved among all metazoans, including humans. The excellent genetic model organism Drosophila melanogaster holds promise for elucidating the molecular mechanisms regulating this fundamental metazoan process. Two prerequisites for such investigations are to clearly define an experimental system to investigate apocrine secretion and to understand the evolutionarily and functional contexts in which apocrine secretion arose in that system. To this end, we recently demonstrated that, in D. melanogaster, the prepupal salivary glands utilize apocrine secretion prior to pupation to deliver innate immune and defense components to the exuvial fluid that lies between the metamorphosing pupae and its chitinous case. This finding provided a unique opportunity to appraise how this novel non-canonical and non-vesicular transport and secretory mechanism is employed in different developmental and evolutionary contexts. Here we demonstrate that this apocrine secretion, which is mechanistically and temporarily separated from the exocytotic mechanism used to produce the massive salivary glue secretion (Sgs), is shared across Drosophilidae and two unrelated dipteran species. Screening more than 30 species of Drosophila from divergent habitats across the globe revealed that apocrine secretion is a widespread and evolutionarily conserved cellular mechanism used to produce exuvial fluid. Species with longer larval and prepupal development than D. melanogaster activate apocrine secretion later, while smaller and more rapidly developing species activate it earlier. In some species, apocrine secretion occurs after the secretory material is first concentrated in cytoplasmic structures of unknown origin that we name "collectors." Strikingly, in contrast to the widespread use of apocrine secretion to provide exuvial fluid, not all species use exocytosis to produce the viscid salivary glue secretion that is seen in D. melanogaster. Thus, apocrine secretion is the conserved mechanism used to realize the major function of the salivary gland in fruitflies and related species: it produces the pupal exuvial fluid that provides an active defense against microbial invasion during pupal metamorphosis.

Defense responses in cowpea elicited by entomopathogenic fungi against <i>Aphis craccivora</i> Koch

Use of entomopathogenic fungi for controlling the aphids is well attempted and further substantiation of interaction of entomopathogenic fungus in cowpea plants against aphid were studied in detail. Bioassays were performed with five fungal isolates against cowpea aphid Aphis craccivora Koch. The results revealed that the isolate Beauveria bassiana (NBAIR) recorded the highest mortality of 94.67% at 120 hr (at 5 days after treatment- DAT). The foliar application of its crude formulation @ 108 spores ml-1 had significant influence on the induction of defense related enzymes and components against A. craccivora infestation in cowpea. Resistant mechanism mediated by entomopathogenic fungi in cowpea against A. craccivora showed sustained and timely induction/ accumulation of defense enzymes. On 4 DAT the enzymes viz., peroxidases, polyphenol oxidases, phenylalanine ammonia lyase, chitinase, catalase and phenolics revealed maximum activity.

Defense Components and Systems

Defense Components and Systems

U.S. missile defense policy in the context of great power competition

American missile defense in the late 1990s began to develop as a protection against the DPRK and Iran. Washington's official approach has evolved over twenty years. Currently, certain segments of the U.S. missile defense policy are officially linked with the confrontation against Russia and China. Even if the Russian or Chinese strategic nuclear forces, due to their size, will never be the main target for U.S. missile defense, the air components of the Chinese and Russian nuclear triads are already in the ‘crosshairs’ of U.S. missile defense. The overall strategy for the use of integrated air and missile defense is evolving. There are a number of features of the qualitative and quantitative development of regional missile defense systems to protect U.S. troops and their allies. The space component of missile defense, even without the creation of orbital missile defenses, is developing in a direction that can threaten strategic stability. The confrontation with North Korea and Iran because of the size of their missile arsenals makes it necessary to integrate offensive and defensive systems with each other. But it is precisely the confrontation with the Russia and China that makes the U.S. to unite offensive missiles, missile defense, air defense, and, in the long term, measures to protect their space assets through architecture of sensors of various types and battle management systems.

EDUCATION AS A TOOL FOR ENSURING NATIONAL SECURITY

The issue of improving the provision of national security of Ukraine by improving the sphere of education has been updated. It has been established that today's conceptual transformational changes taking place in Ukraine and the world require consideration of the field of education as an integral part of the formation of the general field of national security of Ukraine. It is proved that pAmong the various factors of national security, an important role is played by the educational sphere and educational potential, which is a system-forming factor in the life of society and actively affects the state of political, economic, social, defense and other components of security. The reverse statement is also justified: political, economic, defense and other spheres, being system-forming factors of society, determine the conditions for the formation and development of educational potential. National security cannot be ensured only by the means of educational policy, but it cannot be guaranteed in isolation from it.

Expression and role of defense components in Bacillus subtilis treated rice plants against Xanthomonas oryzae pv. oryzae

Expression and role of defense components in Bacillus subtilis treated rice plants against Xanthomonas oryzae pv. oryzae

Peripheral and regional blood bloodstreams lipid peroxidation comparative analysis in women with pelvic venous disorder.

Pelvic venous disorder (PVD) in women is a polyetiological multifactorial disease characterized by a high prevalence (up to 80%), a high risk of infertility, and a progressive recurrent course. Morphological changes of the venous bed occur in PVD, contributing to retrograde blood flow and pelvic phlebohypertension. It is occur due to dynamic hypervolemia and hypertension long-term exposure on the venous wall. However, PVD pathogenesis analysis only from venous hemodynamic disorders position does not explain all mechanisms of the disease development and does not contribute to the treatment measures effectiveness. Currently oxidative stress reactions are considered as the most important markers of the pathological process. The aim of our work was a comparative analysis of lipid peroxidation-antioxidant defense component changes in the peripheral and regional blood flow in women with primary pelvic venous disorder depending on the disease stage. The study involved 137 women of reproductive age (mean age 37.4±9.1 years old) with diagnosed primary PVD divided into 3 groups according to the pathological process stages (stages I, II, III). Data from 30 practically healthy women (mean age 33.5±6.3 years old) were used as controls. Spectrophotometric, fluorometric, immunoassay and statistical methods were used. In patients with PVD stage I in peripheral bloodstream were higher values of SOD and GPO activity; in the regional bloodstream were higher levels of TBARs, SOD, catalase, GPO and lower GSH. In PVD stage II the peripheral bloodstream showed elevated levels of DC, GSH and SOD reduced levels; the regional bloodstream showed higher levels of DC, TBARs, GPO and GSH reduced levels relative to controls. PVD stage III was characterized by: higher levels of DC and TBARs and lower levels of SOD and GSH in the peripheral bloodstream; higher levels of DC, TBARs and lower levels of GSH and catalase in the regional bloodstream compared with control. Thus, the results of our study showed no significant differences in the LPO-AOD system between peripheral and regional bloodstreams in patients with PVD depending on the disease stage. However, negative changes in the redox balance in the regional bloodstream were earlier and were already registered at the first stage of the disease. It is likely that control of antioxidant insufficiency in patients with PVD should be an important component of preventive measures in the early stages and pathogenetic treatment in the pathological process progression, particularly in stage III of the disease.

A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen Tannerella forsythia.

Periodontopathogenic Tannerella forsythia uniquely secretes six peptidases of disparate catalytic classes and families that operate as virulence factors during infection of the gums, the KLIKK-peptidases. Their coding genes are immediately downstream of novel ORFs encoding the 98-132 residue potempins (Pot) A, B1, B2, C, D and E. These are outer-membrane-anchored lipoproteins that specifically and potently inhibit the respective downstream peptidase through stable complexes that protect the outer membrane of T. forsythia, as shown in vivo. Remarkably, PotA also contributes to bacterial fitness in vivo and specifically inhibits matrix metallopeptidase (MMP) 12, a major defence component of oral macrophages, thus featuring a novel and highly-specific physiological MMP inhibitor. Information from 11 structures and high-confidence homology models showed that the potempins are distinct β-barrels with either a five-stranded OB-fold (PotA, PotC and PotD) or an eight-stranded up-and-down fold (PotE, PotB1 and PotB2), which are novel for peptidase inhibitors. Particular loops insert like wedges into the active-site cleft of the genetically-linked peptidases to specifically block them either via a new "bilobal" or the classic "standard" mechanism of inhibition. These results discover a unique, tightly-regulated proteolytic armamentarium for virulence and competence, the KLIKK-peptidase/potempin system.

Copper Super-Dosing Improves Performance of Heat-Stressed Broiler Chickens through Modulation of Expression of Proinflammatory Cytokine Genes.

Continuous exposure to high ambient temperatures brings about a number of oxidative damages in chickens. Copper (Cu), an active component of a number of antioxidative defence components, should arrest these changes to take place although that may not be possible under the standard dosing regimen followed by the industry. To ascertain the optimum dose response that may be beneficial in sustaining the performance of chickens under heat stress (HS), broiler chickens (n = 400) were exposed to high ambient temperature (between 27.2°C and 35.3°C) during 1-35 d. Copper (Cu) as Cu proteinate (Cu-P) at concentrations of 37.5, 75, 112.5, and 150 mg/kg was supplemented to the diet. The negative control (NC) diet did not contain any supplemental Cu. Increasing dietary Cu improved (P < 0.001) body weight, feed intake, and conversion ratio. Serum concentrations of total cholesterol at 21 d (P = 0.009), HDL cholesterol at 35 d (P = 0.008), LDL cholesterol at 21 d (P = 0.015), and triacylglycerol at both 21 d (P = 0.033) and 35 d (P = 0.001) decreased as Cu in the diet increased. As Cu in the diet increased, hemoglobin increased (P = 0.003) at 21 d, and the heterophil to lymphocyte ratio decreased both at 21 d (P = 0.047) and 35 d (P = 0.001). Superoxide dismutase and glutathione peroxidase activities increased when dietary Cu increased to 150 mg/kg (P < 0.01). Liver Cu at 35 d increased linearly with the dose of Cu in the diet (P = 0.0001). Selected bacteria were enumerated in the digesta to ascertain if Cu super-dosing affected their population in any way in the absence of any enteric challenge. Escherichia coli and total Salmonella numbers decreased (P = 0.0001), and total Lactobacillus increased (P = 0.0001) proportionately with dietary Cu. Interleukin-6 and tumour necrosis factor-α gene expression increased linearly (P = 0.0001) as Cu in the diet increased though the response plateaued at 112.5 mg/kg. It was concluded from the present experiment that during conditions of impending HS, dietary supplementation of 112.5 to 150 mg Cu/kg diet as Cu-P may be a novel strategy to alleviate the negative effects of HS without involving any apparent risk of Cu toxicity.

Strategic Role of the Defense Industry in Answering the Needs of KRI Capability C4ISR to Achieve Maritime Security in Indonesian National Jurisdictions

The currently growing and complex maritime security threat is marked by the Coronavirus outbreak, which is thought to spread quickly. This virus threat can mean Hybrid Warfare but can also mean proxy where this type of threat can be exploited or used by parties who intend to invest their interests in Indonesia. This threat must be a concern of all countries, and cooperation at sea between countries is needed to overcome it. The Indonesian Navy sees the importance of increasing capabilities in the field of utilizing C4ISR technology (Command, Control, Computer, Communication, Intelligence, Surveillance, And Recognition) and how to integrate it into a single unit that can operate optimally within the framework of maritime defense and security of the unitary state of the Republic of Indonesia. Furthermore, cooperation with the Navy and all naval stakeholders is also needed to build collaboration in realizing maritime domain awareness (MDA) in the national region. The importance of Indonesia as a barometer of regional maritime security, namely; as a measure of the independence of Indonesia's ability to face naval security threats, measuring patterns, methods, and technology of Indonesia's marine security apparatus in dealing with threats, as well as predicting trends in maritime security threats that occur. As the main component of national defense, the Navy is required to carry out capacity building in marine protection and security, So that the defense i

Molecular Cloning and Characterization of a Novel Antimicrobial Peptide from the Skin of Kaloula pulchra.

Bacterial resistance to all currently available conventional antibiotics has caused a global public health crisis and led to an imperative search for new agents. Antimicrobial peptides (AMPs) are essential components of host innate immune defense against microbial invasions. The objective of this study was to report a novel AMP, brevinin-2KP, from the skin of the black Kaloula pulchra frog and describe its structural and biological characterization. The physical and chemical parameters of brevinin-2KP were predicted with the ExPASy Bioinformatics Resource Portal. The assembled sequences were aligned with ClustalW, and the phylogenetic tree was constructed using Mega. Circular dichroism (CD) experiments were carried out to identify the secondary structure and the stability of peptide in different solvent environments. The cytotoxicity of brevinin-2KP was evaluated by the MTT test. To determine antibacterial activity of brevinin- 2KP, a standard two-fold broth dilution method was used. SEM was carried out to observe the morphological change in the bacterial treated by brevinin-2KP. The live/dead bacterial viability was measured with a LIVE/DEAD® BacLight kit. Histamine release and mast cell degranulation assays were performed. The precursor of brevinin-2KP contains 72 amino acid residues, including a conserved signal peptide, acidic propeptide with KR residues, and mature peptide with a sequence of GVITDALKGAAKTVAAELLKKAHCKLTNSC. Phylogenetic analysis based on the amino acid sequences of 34 brevinin-2 peptides from 30 anuran species demonstrates that K. pulchra is genetically closely related to the genus Hylarana. The CD spectra analysis indicates that brevinin-2KP adopts random coil in the water and an organized α-helical conformation in SDS solution. Further, this secondary structure is stable under high salt and high-temperature conditions. Brevinin-2KP is weakly active towards the tested Gram-positive and Gram-negative bacteria as well as fungi due to its membranolytic action. Moreover, brevinin-2KP inhibits the proliferation of several mammal cells with IC50 values ranging from 3.27 to 59.75 μM. In addition, brevinin-2KP promotes degranulation and histamine release of mast cells, indicating that it is involved in the inflammatory response. This is the first report on AMP identified from the skin of K. pulchra. Brevinin-2KP adopts a typical amphipathic α-helix conformation in membrane mimic environment and shows antimicrobial and antitumor activities by potential membranolytic mechanism. In addition, brevinin-2KP can promote degranulation and histamine release of mast cells. Brevinin-2KP is expected to become a good drug temple molecule.

Amyotrophic lateral sclerosis disease-related mutations disrupt the dimerization of superoxide dismutase 1 - A comparative molecular dynamics simulation study

More than 150 genes are involved in amyotrophic lateral sclerosis (ALS), with superoxide dismutase 1 (SOD1) being one of the most studied. Mutations in SOD1 gene, which encodes the enzyme SOD1 is the second most prevalent and studied cause of familial ALS. SOD1 is a ubiquitous, homodimeric metalloenzyme that forms a critical component of the cellular defense against reactive oxygen species. Several mutations in the SOD1 enzyme cause misfolding, dimerization instability, and increased aggregate formation in ALS. However, there is a lack of information on the dimerization of SOD1 monomers and the mechanistic underpinnings on how the pathogenic mutations disrupt the dimerization mechanism. Here, we presented microsecond-scale molecular dynamics (MD) simulations to unravel how interface-based mutations compromise SOD1 dimerization and provide mechanistic understanding into the corresponding process using WT and three interface-based mutant systems (A4V, T54R, and I113T). Structural stability analysis showed that the mutant systems displayed disparate variations in the catalytic sites which may directly alter the stability and activity of the SOD1 enzyme. Based on the dynamic network analysis and principal component analysis, it has been identified that the mutations weakened the correlated motions along the dimer interface and altered the protein conformational behavior, thus weakening the stability of dimer formation. Moreover, the simulation results identified crucial residues such as G51, D52, G114, I151, and Q153 in establishing the dimerization interaction network, which were weakened or absent in the presence of interfacial mutants. Surface potential analysis on mutant systems also displayed changes in the dimerization potential, thus showing the unfavorable dimer formation. Furthermore, network analysis identified the hotspot residues necessary for SOD1 signal transduction which were surprisingly found in the catalytic sites rather than the anticipated dimerization interface.

Показники прооксидантно-антиоксидантної системи і білкового обміну у щурів, після впливу слабких електромагнітних полів

The purpose of the work was to study the state of the components of the prooxidant-antioxidant system and indicators of protein metabolism in animals after a long period after exposure to weak electromagnetic fields. Materials and methods. The experiment was carried out on three-month-old white outbred rats. The animals were exposed to low-intensity electromagnetic radiation in the centimeter range for 2 months, 4 hours daily. The study of biochemical parameters of blood serum was carried out 3 months after the end of the experimental exposure. When conducting the research, an emitter in the form of a rectangular horn with a base area of 875 cm was used. Energy radiation was expressed in the power flow density in the area where the experimental animals were located. In the comparison group (n=10), animals were placed in a similar chamber every day, but were not exposed to electromagnetic radiation. Research was conducted in the first half of the day, taking into account circadian rhythms. The analysis of biochemical parameters of blood serum was carried out 3 months after the end of exposure, that is, for rats aged 8 months. Results and discussion. It was revealed that in animals exposed to weak electromagnetic radiation, after a long period after the cancellation of the action, there is an imbalance in the prooxidant-antioxidant system; activation of the non-enzymatic link of antioxidant protection is observed – an increase in the level of s-nitrosothiols against the background of a decrease in the level of lipid peroxidation, which, in addition to a destructive effect on the cell membrane, is a necessary element in maintaining the system of renewal of functionally important component of the lipid layer of cell membranes. The experimentally established dysproteinemia (decrease in the α1 fraction and increase in the α2 fraction of globulins) in animals of the main group may indicate a specific change in the enzymatic spectrum of the synthesis of these proteins in the liver. The activation of antioxidant defense components that we discovered is probably a protective measure aimed at maintaining homeostasis after prolonged exposure to electromagnetic radiation. Conclusion. A decrease in the level of final products of protein metabolism was revealed: creatinine and urea, which suggests a decrease in the rate of protein catabolism. It is concluded that in animals, after a long period after exposure to weak electromagnetic fields of the centimeter range, the level of lipid peroxidation is reduced, specific changes in the indicators of protein metabolism are noted, indicating a decrease in the level of their catabolism. It is suggested that this may be related to a decrease in total muscle mass