Structural Complex Research Articles

Synthesis, spectral studies, DFT, biological evaluation, molecular docking and dyeing performance of 1-(4-((2-amino-5-methoxy)diazenyl)phenyl) ethanone complexes with some metallic ions

Four Co(II), (C1); Ni(II), (C2); Cu(II), (C3) and Zn(II), (C4) chelates have been synthesized with 1-(4-((2-amino-5‑methoxy)diazenyl)phenyl)ethanone ligand (L). The produced compounds have been identified by using spectral studies, elemental analysis (C.H.N.O), conductivity and magnetic properties. The produced metal chelates were studied using molar ratio as well as sequences contrast types. Rate of concentration (1 ×10−4 - 3 ×10−4 Mol/L) sequence Beer's law. Compound solutions have been noticed height molar absorptivity. The free of ligand and metal chelates had been applied as disperse dyes on cotton fabrics. Furthermore, the antibacterial activity of the produced compounds against various bacteria had been investigated. For the gained datum, a tetrahedral geometrical structure has been suggested for each primed complex. Molecular docking investigation was carried out to ascertain the inhibitory action of the studied compounds against 1HNJ protein, the target enzyme for the antimicrobial agents. The findings showed that, when compared to other compounds, (C1) has the highest binding affinity. Therefore, these molecules might make good candidates for antimicrobials. The quantum chemical parameters are calculated, and the molecular structure complexes were theoretically optimized.

Allosteric regulation and crystallographic fragment screening of SARS-CoV-2 NSP15 endoribonuclease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The NSP15 endoribonuclease enzyme, known as NendoU, is highly conserved and plays a critical role in the ability of the virus to evade the immune system. NendoU is a promising target for the development of new antiviral drugs. However, the complexity of the enzyme's structure and kinetics, along with the broad range of recognition sequences and lack of structural complexes, hampers the development of inhibitors. Here, we performed enzymatic characterization of NendoU in its monomeric and hexameric form, showing that hexamers are allosteric enzymes with a positive cooperative index, and with no influence of manganese on enzymatic activity. Through combining cryo-electron microscopy at different pHs, X-ray crystallography and biochemical and structural analysis, we showed that NendoU can shift between open and closed forms, which probably correspond to active and inactive states, respectively. We also explored the possibility of NendoU assembling into larger supramolecular structures and proposed a mechanism for allosteric regulation. In addition, we conducted a large fragment screening campaign against NendoU and identified several new allosteric sites that could be targeted for the development of new inhibitors. Overall, our findings provide insights into the complex structure and function of NendoU and offer new opportunities for the development of inhibitors.

CLINICAL AND PATHOGENETIC FEATURES OF DAMAGE TO THE NERVOUS SYSTEM AT THE INITIAL CLINICAL STAGES OF HIV-INFECTION

The aim of the study – investigating the features of clinical symptoms in HIV-positive people in the early stages of the disease and their pathogenetic justification.
 The study used theoretical methods based on the analysis and synthesis of studying the information of the modern world from the PubMed and Scopus databases, clinical observations, as well as deductive-inductive methods.
 Conclusions. As a result of the war in Ukraine, the epidemiological control of infectious diseases on the territory of the country was violated. HIV-infection and the absence or atypicality of its clinical symptoms in infected patients deserve special attention, which is based on a detailed understanding of the pathological processes of neuroAIDS. Damage to astrocyte cells disrupts the connection of cells of the structural and functional complex of the brain with other cells and forms the fundamental basis for understanding clinical symptoms. Most often in the form of: neuropsychic, cognitive somatic and neurological disorders. The pathogenic effect of the virus contributes to spasm of cerebral microvessels, is the cause of local hypoxic lesions, microstrokes, and in late cases – lacunar cerebral infarcts. The active involvement of brain cells in the pathogenesis of HIV-infection has been confirmed by many studies. Along with standard diagnostic methods, it is advisable to use psychoneurological and cognitive tests and scales. 
 A number of shortcomings have been identified that can reduce the reliability of diagnostic studies when establishing a diagnosis. 
 Understanding the pathogenetic picture will allow choosing «indicators» for the general diagnostic scheme and increasing the probability of establishing the correct diagnosis, adjusting ART and predicting the further development of the disease.

The importance of theory at the Information Systems Journal

The importance of theory at the <i>Information Systems Journal</i>

A helper antibody based competitive fluorescence immunochromatographic assay for quantitative detection of florfenicol in poultry eggs.

Florfenicol (FF) is a chloramphenicol analogue used in animals, and florfenicol amine (FFA) is the main metabolite of FF. However, their residues in agricultural products are harmful to human health. A highly specific and sensitive assay for FF/FFA detection needs to be developed since the traditional detection methods are low sensitive. In this study, a new method for rapid quantification of FF/FFA in poultry eggs by fluorescent immunochromatographic assay (HAFIA) was established. The triple antibodies including a primary monoclonal antibody (mAb) specific to the targets FF and FFA, a secondary polyclonal antibody (pAb) labeled with Europium nanoparticles (EuNPs) and a helper monoclonal antibody (hAb) reacting with pAb but not react with mAb or target antigen are designed, which can form structural aggregation complexes in microwells with a single step of reactions. By loading the reaction sample solution, the triple-antibodies (mAb-pAb-hAb)-EuNPs complexes migrate to the test (T) line on nitrocellulose membrane of testing strip, which are competitively captured by the immobilized FF-BSA conjugates on the membrane and the FF/FFA targets in sample solution. Fluorescence on T line is read by a portable fluorescent strip reader in 10 min, and the result is given by the ratio of fluorescent intensity on T line than control (C) line. This new fluorescent testing strip with triple-antibody complexes' amplification signal has 50-fold higher sensitivity than conventional CG-LFIAs, and can detect as low as 0.01 ng/mL florfenicol and 0.1 ng/mL florfenicol amine targets from egg samples. The developed competitive fluorescent immunochromatography method based on auxiliary antibodies has the advantages of high sensitivity and specificity for the rapid and quantitative detection of FF/FFA in poultry eggs.

Effects of structural complexity on epifaunal assemblages associated with two intertidal Mediterranean seaweeds

Brown foundation seaweeds are key elements increasing substrate heterogeneity and shaping the biodiversity in rocky coastal ecosystems. They are, however, vulnerable species that are declining due to multiple anthropogenic and climate change stressors, leading to a shift to less structural complex habitats. We investigate the role of structural attributes of two intertidal macroalgae, Ericaria amentacea and Laurencia obtusa, in shaping the abundance and diversity of their associated epifaunal assemblages. For this aim, we measured seaweeds’ biomass, thallus volume and length (used here as proxy of substrate complexity), and explored which seaweeds’ substrate attribute explained better variation of epifaunal assemblages. Results showed that E. amentacea was more complex than L. obtusa and hosted a higher number of epifaunal individuals. However, unlike that expected, the epifaunal assemblage of L. obtusa was more structured with higher Shannon–Wiener diversity and Pielous’ evenness. Our findings indicate that, besides seaweed’s substrate attributes, other mechanisms such as wave action and chemical defense might play a role in structuring epifaunal assemblages. We suggest that a shift from E. amentacea to L. obtusa population could have effect on structure and abundance of associated epifaunal assemblages. Certainly, further investigations are needed to clear up the consequences of these changes.

Spectra and characteristics of somatic mutations induced by ionizing radiation in hematopoietic stem cells

Spectra and frequencies of spontaneous and X-ray-induced somatic mutations were revealed with mouse long-term hematopoietic stem cells (LT-HSCs) by whole-genome sequencing of clonal cell populations propagated invitro from single isolated LT-HSCs. SNVs and small indels were the most common types of somatic mutations, and increased up to twofold to threefold by whole-body X-irradiation. Base substitution patterns in the SNVs suggested a role of reactive oxygen species in radiation mutagenesis, and signature analysis of single base substitutions (SBS) revealed a dose-dependent increase of SBS40. Most of spontaneous small deletions were shrinkage of tandem repeats, and X-irradiation specifically induced small deletions out of tandem repeats (non-repeat deletions). Presence of microhomology sequences in non-repeat deletions suggested involvement of microhomology mediated end-joining repair mechanisms as well as nonhomologous end-joining in radiation-induced DNA damages. We also identified multisite mutations and structural variants (SV), i.e., large indels, inversions, reciprocal translocations, and complex variants. The radiation-specificity of each mutation type was evaluated from the spontaneous mutation rate and the per-Gy mutation rate estimated by linear regression, and was highest with non-repeat deletions without microhomology, followed by those with microhomology, SV except retroelement insertions, and multisite mutations; these types were thus revealed as mutational signatures of ionizing radiation. Further analysis of somatic mutations in multiple LT-HSCs indicated that large fractions of postirradiation LT-HSCs originated from single LT-HSCs that survived the irradiation and then expanded invivo to confer marked clonality to the entire hematopoietic system, with varying clonal expansion and dynamics depending on radiation dose and fractionation.

A COMPARATIVE STUDY: LISFRANC JOINT INJURIES TREATED WITH PRIMARY ARTHRODESIS VERSUS OPEN REDUCTION INTERNAL FIXATION

Background: Tarsometatarsal joint is a structural complex which allows for effective force transfer and propulsion during gait. Lisfranc joint injuries sometimes can be missed, or delayed treatment may lead to disability with chronic pain and deformity of tarsometatarsal joint. There is a controversy between primary arthrodesis versus open reduction with internal xation as to which is superior treatment with better outcome for these injuries. To compare primary arthrodesis versus open reduction with internal Aim Materials and Method xation for Lisfranc joint injuries. A comparative observational study was conducted from August 2020- October 2022 at AVMC &amp; H, Pondicherry. 21 patients were included in the study. All were followed up for a minimum of 6months. In our study, According AOFAS s Results core we had excellent to good outcome in 90% patients treated with Primary arthrodesis than open reduction internal xation Conclusion In our study, we conclude that in south Indian population, shows that primary arthrodesis has better functional outcome than Open reduction and internal xation for Lisfranc joint injury. Since the sample size is limited and the duration of study is short, further study is need with larger population.

Evolution of the Keivy domain in the Precambrian

Detailed geological and petrogeochemical studies carried out using the techniques developed by the authors have made it possible to complete the picture of the formation of supracrustal complexes of the Keivy structure. The studies have shown that the metasedimentary complexes of the Chervurt and Vykhchurt suites were formed mainly due to the material of the underlying strata. In the development of the Vykhchurt Formation, starting from its upper part, the material of the domains surrounding the Keivy takes an active part. The authors have come to the conclusion that at least the middle part of the Keivy section was formed as a result of washing and redeposition of the material of the structure itself, it confirms the conclusions about the presence of redeposited weathering crusts within the Keivy. The results obtained testify to the correctness of the earlier conclusion about the formation of the Keivy structure under conditions most similar to the middle massifs, and to a certain extent explain the formation of a giant deposit of aluminum raw materials within the Keivy.

Structural basis for enzymatic terminal C–H bond functionalization of alkanes

Alkane monooxygenase (AlkB) is a widely occurring integral membrane metalloenzyme that catalyzes the initial step in the functionalization of recalcitrant alkanes with high terminal selectivity. AlkB enables diverse microorganisms to use alkanes as their sole carbon and energy source. Here we present the 48.6-kDa cryo‐electron microscopy structure of a natural fusion from Fontimonas thermophila between AlkB and its electron donor AlkG at 2.76 Å resolution. The AlkB portion contains six transmembrane helices with an alkane entry tunnel within its transmembrane domain. A dodecane substrate is oriented by hydrophobic tunnel-lining residues to present a terminal C–H bond toward a diiron active site. AlkG, an [Fe–4S] rubredoxin, docks via electrostatic interactions and sequentially transfers electrons to the diiron center. The archetypal structural complex presented reveals the basis for terminal C–H selectivity and functionalization within this broadly distributed evolutionary class of enzymes.

Combinatorial approach to fabricate silica doped polyvinyl alcohol/hydroxyapatite/carrageenan nanocomposite for bone regeneration applications

AbstractBone tissue engineering is a dominating approach for the fabrication of nanocomposite bone implants with superior biocompatibility and low toxicity to the surrounding tissues. Here, in this report ternary nanocomposites integrating nanohydroxyapatite/κ‐carrageenan/silica doped polyvinyl alcohol in three different ratios, that is, 60/30/10 (HCP1), 60/20/20 (HCP2), and 60/10/30 (HCP3) was constructed and a binary system comprised of nanohydroxyapatite and κ‐carrageenan was also prepared for analyzing and comparing their bone regeneration potential. The samples were characterized by various physico‐chemical techniques such as infra‐red spectroscopy, which furnished details about structural functionalities and complex formation. Rough surface morphology and dispersed particle size distribution of developed nanocomposites were revealed by scanning electron microscopy and electron transmission microscopy, respectively. Thermogravimetric analysis and differential temperature analysis revealed higher thermal stability of HCP3 nanocomposite with total weight loss of 10% and X‐ray diffraction analysis revealed average crystallite size of 15 nm for HCP3 nanocomposite. Bioactivity and biocompatibility of fabricated nanocomposites were deduced with the help of biological techniques. HCP3 manifested cell viability above 100% at 2 μg/mL concentration and exhibited hemolysis below 3% at all tested concentration favoring cell growth with minimum cytotoxicity. HCP3 also exhibited efficient apatite layer deposition, optimum swelling ability and improved biodegradability (~30%) and anti‐bacterial activity predicting it as a promising nanocomposite implant for future orthopedic applications.

Prediction of maximum tensile stress in plain-weave composite laminates with interacting holes via stacked machine learning algorithms: A comparative study

Plain weave composite is a long-lasting type of fabric composite that is stable enough when being handled. Open-hole composites have been widely used in industry, though they have weak structural performance and complex design processes. An extensive number of material/geometry parameters have been utilized for designing these composites, thereby an efficient computational tool is essential for that purpose. Different Machine Learning (ML) tools were integrated to obtain the model with the highest accuracy considering the maximum tensile stress of composite plates with two interacting notches while comparing the effectiveness of each technique. Finite Element (FE) simulations were carried out inside the ABAQUS software by employing python macro code to provide a data-rich framework (8960 data). The predictions given by ML methods were compared with the data given by the numerical simulations. An evolutionary algorithm (TPOT) and automatic neural network search (AuoKeras) were utilized for that purpose. An automatic grid search technique was employed to select the best method which could predict the material attribute target values (maximum stress) for different tests. 1% of the data was given as training while 99% was for testing to ensure the robustness of the model. It was concluded that the model containing the Gradient Boosting Regression (GBR), PolyFeatures, and LassoLarsCV algorithms outperformed other ML combinations and Artificial Neural Networks (ANN) for predicting the target value. The coefficient of determination (R2) and root mean square error (RMSE) of the proposed model were 0.97 and 253 respectively. Hence, this model could be utilized for prospective predictions in this type of materials and geometry by providing further reduction of the computational time and labor cost with high accuracy.

КОНЦЕПТУАЛЬНА МОДЕЛЬ ПЛАТЕЖІВ ЗА ЕКОСИСТЕМНІ БЛАГА: НАУКОВИЙ ПОШУК НОВИХ ІНСТРУМЕНТІВ ЕКОЛОГІЧНОЇ КОМПЕНСАЦІЇ У ПОВОЄННИЙ ПЕРІОД

Уперше репрезентовано концепт платежів за екосистемні блага як загальнонаукову модель, що відображає процес економічного форматування в грошові еквіваленти цінності продуктів (товарів, ресурсів) і послуг, які генеруються екосистемними активами, утворюючи їх дохідний внесок у людський добробут. Зокрема, послідовно висвітлено теоретико-методологічні засади формування концепту платежів за екосистемні блага; розкрито змістовне наповнення цих платежів як цілісного структурно-функціонального комплексу новітніх монетарних інструментів механізму екологічної компенсації, нині сформованого в зарубіжних практиках фінансування природовідтворювальних заходів. Показано, що основними інструментами (елементами) платежів за екосистемні блага є: прямі платежі (виплати) за надання, споживання, користування екосистемними функціями, продуктами (товарами, ресурсами) і послугами, що генеруються екосистемами; виплати за пріоритетне надання (заміщення) певних видів екосистемних благ; субсидії для підтримання продуктивного стану екосистем їх власниками («продавцями»), у тому числі через спеціально створені накопичувальні фінансові фонди; пільгове оподаткування природоохоронних і природовідновлювальних заходів власників («продавців») благ, що генеруються належними їм територіальними екосистемами; компенсаційні виплати за відшкодування збитків від детеріорації стану, якості екосистем і продукування ними екосистемних благ. Наведено приклад реалізації платежів за надання екосистемних послуг з регулювання клімату типу PES/REDD у рамках пілотного проєкту в Сполучених Штатах Мексики, який переконливо демонструє, що саме в такий спосіб –– через запровадження цих інструментів механізму екологічної компенсації –– досягається узгодження конфліктів інтересів між різними групами стейкхолдерів щодо постачання, споживання і користування екосистемними благами, що сприяє подальшому спрямуванню їх інтересів на попередження втрати послуг екосистем, якісного стану довкілля. Показано еколого-економічну значущість розроблення концептуальної моделі платежів за екосистемні блага; доведено нагальність опрацювання й започаткування організаційних заходів вищого управлінського рівня щодо запровадження цього інструментарію механізму екологічної компенсації в українську інституціонально-регуляторну базу природокористування в повоєнному періоді.

Molecular structure and linear-non linear rheology relation of rice starch during milky, dough, and mature stages

Immature rice has potential to be used as healthy food. The relation between molecular structure and rheological properties was investigated. The lamellar repeating distance (8.42–8.63 nm) and crystalline thickness (4.60–4.72 nm) were not different among stages indicating a complete lamellar structure even at early stage. The relative crystallinity was higher in dough (39.62 %) than milky (36.69 %) and mature starch (35.22 %) caused by molecular structure, amylose, and amylose-lipid complex. The short amylopectin branched chains (A and B1) in dough starch were easily entangled resulted in higher Payne effect and elastic dominant. Dough starch paste exhibited higher G′Max (738 Pa) than milky (685 Pa) and mature (645 Pa) starch. In a non-linear viscoelastic regime, small strain hardening was found in milky and dough starch. Mature starch showed the highest plasticity and shear thinning at high-shear strains as the long-branched chains (B3) microstructure was disrupted, disentangled, followed by chain orientation along shear.

Geochemical features of HC- occurrence in carbonates of the Minyar formation of the Upper Riphean, Bashkir Meganticlinorium, Southern Urals

The results of a geochemical study of organic matter found in carbonate deposits of a typical section of the Minyar formation of the Upper Riphean, exposed within the Karatau structural complex in the western part of the Bashkir meganticlinorium, are presented.&#x0D; Analytical methods of gas chromatography and chromato-mass spectrometry in extracted hydrocarbons have been used to diagnose diamantanes, alkanes and specific biomarkers – tricyclic terpanes, gopanes and steranes. The thermal maturity corresponding to the upper part of the oil window is determined by the diamantanes. The quantitative ratios of other hydrocarbons strongly depend on the facies nature of carbonates – in thin-layered lagoon carbonates, where there are significantly more of them, they are recognized as autochthonous, in the stromatolite bioherm located next to them, light alkanes were lost, organic matter was probably subject to consedimentary biodegradation due to periodic subaeral exposure. Dibenzothiophene, an organosulfur biomarker, was also found in organic matter, which can be used to assess the content of sulfates in the sedimentation basin. The concentration of dibenzothiophene is significantly higher than the concentrations in the occurrence of hydrocarbons in Neoproterozoic sediments of other regions of the world, which indicates the existence of strong regional differences in the content of sulfate in Late Precambrian seawater.

Design, synthesis, and mechanism of action of novel μ-conotoxin KIIIA analogues for inhibition of the voltage-gated sodium channel Nav1.7

μ-Conotoxin KIIIA, a selective blocker of sodium channels, has strong inhibitory activity against several Nav isoforms, including Nav1.7, and has potent analgesic effects, but it contains three pairs of disulfide bonds, making structural modification difficult and synthesis complex. To circumvent these difficulties, we designed and synthesized three KIIIA analogues with one disulfide bond deleted. The most active analogue, KIIIA-1, was further analyzed, and its binding pattern to hNav1.7 was determined by molecular dynamics simulations. Guided by the molecular dynamics computational model, we designed and tested 32 second-generation and 6 third-generation analogues of KIIIA-1 on hNav1.7 expressed in HEK293cells. Several analogues showed significantly improved inhibitory activity on hNav1.7, and the most potent peptide, 37, was approximately 4-fold more potent than the KIIIA Isomer I and 8-fold more potent than the wildtype (WT) KIIIA in inhibiting hNav1.7 current. Intraperitoneally injected 37 exhibited potent invivo analgesic activity in a formalin-induced inflammatory pain model, with activity reaching ∼350-fold of the positive control drug morphine. Overall, peptide 37 has a simplified disulfide-bond framework and exhibits potent invivo analgesic effects and has promising potential for development as a pain therapy in the future.

Heterometallic uranyl (hydroxyethyl)iminodiacetic acid (heidi) complexes: Molecular models for U(VI) uptake in complex media.

Amidoximated absorbents (AO-PAN) effectively remove U(VI) from aqueous solution, but previous studies reported more variability for complex natural waters that contain additional confounding ions and molecules. Ternary phases containing U(VI), M(III) (M = Fe(III), Al(III), Ga(III)), and organic molecules exist under these conditions and cause heterogeneous U(VI) uptake on AO-PAN. The goal of the current study is to provide additional insights into the structural features ternary complexes using N-(2-hydroxyethyl)-iminodiacetic acid (HEIDI) as the model organic chelator and explore the relevance of these species on U(VI) capture. Three model compounds ([(UO2)(Fe)2(μ3-O)(C6NO5H8)2(H2O)4] (UFe2), ([(UO2)(Al)2(μ2-OH)(C6NO5H8)2(H2O)3] (UAl2) and [(UO2)(Ga)2(μ2-OH)(C6NO5H8)2(H2O)3] (UGa2)) were characterized by single-crystal X-ray diffraction. Raman spectra of the model compounds were compared with solution data and the ternary phases were noted in the case of Al(III) and Ga(III), but not in the Fe(III) system. U(VI) adsorption onto AO-PAN was not impacted by the presence of HEIDI or the trivalent metal species.

A new method for classifying and segmenting material microstructure based on machine learning

The microstructural characteristics of materials determine their service performance. Therefore, the rapid identification of material microstructure and the accurate extraction of feature parameters are significant for the research and application of materials. However, most materials have diverse structure types and complex microstructures. With the gradual maturity of computer vision technology, it is increasingly being applied to studying material images. In this paper, a neural network-based material microstructure recognition and semantic segmentation model is designed to automatically identify and classify titanium alloy structures and then adaptively process images and extract features to overcome the challenges of efficient recognition and extraction of multiple structures of materials. The study completed the recognition of 2275 images of 15 types of titanium alloys through data set preparation, image preprocessing, model building, and parameter tuning, followed by image segmentation of morphologically processed images and labels based on U-net. Finally, connected domain computation successfully extracted the feature covariates in multiple structures of titanium alloys. This work demonstrates the application of data mining technology in metal microstructure image research and the implementation process. It completes the identification and characterization of the complex microstructure of the material.

Aggregation of nucleobases and metabolites: Adenine-theobromine trimers.

The selection of cytosine, guanine, thymine, and adenine as components of the information biopolymers was a complex process influenced by several factors. Among them, the intermolecular interactions may have played a determinant role. Thus, a deep understanding of the intermolecular interactions between nucleobases and other prebiotic molecules may help understand the first instants of chemical evolution. Following this hypothesis, we present here a combined spectroscopic and computational study of theobromine2-adenine and thebromine-adenine2 trimers. While adenine is a nucleobase, theobromine was probably part of the prebiotic chemistry. The trimers were formed in jets and probed by a combination of UV and IR spectroscopic techniques. The spectra were interpreted in light of the predictions obtained using density-functional methods. The results suggest the existence of a subtle balance between formation of hydrogen bonds and π-π interactions. Thus, while theobromine2-adenine tends to form complex in stacked structures, theobromine-adenine2 prefers formation of planar structures, maximizing the interaction by hydrogen bonds. The small energy difference between planar and stacked structures highlights the importance of accurately modeling the dispersion forces in the functionals to produce reliable predictions.

In Candida glabrata, ERMES Component GEM1 Controls Mitochondrial Morphology, mtROS, and Drug Efflux Pump Expression, Resulting in Azole Susceptibility

Mitochondrial dysfunction or morphological abnormalities in human pathogenic fungi are known to contribute to azole resistance; however, the underlying molecular mechanisms are unknown. In this study, we investigated the link between mitochondrial morphology and azole resistance in Candida glabrata, which is the second most common cause of human candidiasis worldwide. The ER-mitochondrial encounter structure (ERMES) complex is thought to play an important role in the mitochondrial dynamics necessary for mitochondria to maintain their function. Of the five components of the ERMES complex, deletion of GEM1 increased azole resistance. Gem1 is a GTPase that regulates the ERMES complex activity. Point mutations in GEM1 GTPase domains were sufficient to confer azole resistance. The cells lacking GEM1 displayed abnormalities in mitochondrial morphology, increased mtROS levels, and increased expression of azole drug efflux pumps encoded by CDR1 and CDR2. Interestingly, treatment with N-acetylcysteine (NAC), an antioxidant, reduced ROS production and the expression of CDR1 in Δgem1 cells. Altogether, the absence of Gem1 activity caused an increase in mitochondrial ROS concentration, leading to Pdr1-dependent upregulation of the drug efflux pump Cdr1, resulting in azole resistance.