Role Of Mg2 Research Articles

Simulations predict preferred Mg2+ coordination in a nonenzymatic primer-extension reaction center

The mechanism by which genetic information was copied prior to the evolution of ribozymes is of great interest because of its importance to the origin of life. The most effective known process for the nonenzymatic copying of an RNA template is primer extension by a two-step pathway in which 2-aminoimidazole-activated nucleotides first react with each other to form an imidazolium-bridged intermediate that subsequently reacts with the primer. Reaction kinetics, structure-activity relationships, and X-ray crystallography have provided insight into the overall reaction mechanism, but many puzzles remain. In particular, high concentrations of Mg2+ are required for efficient primer extension, but the mechanism by which Mg2+ accelerates primer extension remains unknown. By analogy with the mechanism of DNA and RNA polymerases, a role for Mg2+ in facilitating the deprotonation of the primer 3′-hydroxyl is often assumed, but no catalytic metal ion is seen in crystal structures of the primer-extension complex. To explore the potential effects of Mg2+ binding in the reaction center, we performed atomistic molecular dynamics simulations of a series of modeled complexes in which a Mg2+ ion was placed in the reaction center with inner-sphere coordination with different sets of functional groups. Our simulations suggest that coordination of a Mg2+ ion with both O3′ of the terminal primer nucleotide and the pro-Sp nonbridging oxygen of the reactive phosphate of an imidazolium-bridged dinucleotide would help to pre-organize the structure of the primer/template substrate complex to favor the primer-extension reaction. Our results suggest that the catalytic metal ion may play an important role in overcoming electrostatic repulsion between a deprotonated O3′ and the reactive phosphate of the bridged dinucleotide and lead to testable predictions of the mode of Mg2+ binding that is most relevant to catalysis of primer extension.

Sustainable energy recovery from salt-lake brines through a novel selective reverse electrodialysis process

The salinity gradient energy (SGE) in salt-lake brines can be exploited as a sustainable energy source through reverse electrodialysis (RED). However, the composition of brines is notably intricate. In order to avoid the adverse effects of multivalent cations on RED in brines, we introduced a novel selective reverse electrodialysis (SRED) here. The results demonstrate that when increasing the salinity ratio between high and low concentration feeds (HCFs, LCFs) from 20 to 60, the SRED maximal maximum power density (Pd,max) improves from 0.069 to 0.109 W/m2. The feed salinity has less obvious effect on SRED. Moreover, the role of Mg2+ on the adverse effects is regulated. The maximal Pd,max of SRED is 1.13 ∼ 1.23 times higher than that of the conventional RED at the Mg2+ concentrations of 4861.00 ∼ 14583.00 ppm in HCFs and 40.51 ∼ 121.53 ppm in LCFs. This suggests that SRED is a feasible and efficient strategy for capturing SGE in salt-lake brines.

Insights into the role of Mg2+ in nucleosomal unstacking and unwrapping: A single-molecule study

Insights into the role of Mg2+ in nucleosomal unstacking and unwrapping: A single-molecule study

Ratiometric Fluorescent Sensors Illuminate Cellular Magnesium Imbalance in a Model of Acetaminophen-Induced Liver Injury.

Magnesium(II) plays catalytic, structural, regulatory, and signaling roles in living organisms. Abnormal levels of this metal have been associated with numerous pathologies, including cardiovascular disease, diabetes, metabolic syndrome, immunodeficiency, cancer, and, most recently, liver pathologies affecting humans. The role of Mg2+ in the pathophysiology of liver disease, however, has been occluded by concomitant changes in concentration of interfering divalent cations, such as Ca2+, which complicates the interpretation of experiments conducted with existing molecular Mg2+ indicators. Herein, we introduce a new quinoline-based fluorescent sensor, MagZet1, that displays a shift in its excitation and emission wavelengths, affording ratiometric detection of cellular Mg2+ by both fluorescence microscopy and flow cytometry. The new sensor binds the target metal with a submillimolar dissociation constant─well suited for detection of changes in free Mg2+ in cells─and displays a 10-fold selectivity against Ca2+. Furthermore, the fluorescence ratio is insensitive to changes in pH in the physiological range, providing an overall superior performance over existing indicators. We provide insights into the metal selectivity profile of the new sensor based on computational modeling, and we apply it to shed light on a decrease in cytosolic free Mg2+ and altered expression of metal transporters in cellular models of drug-induced liver injury caused by acetaminophen overdose.

Unexpected significance of magnesium ion in the coupling effect of mixed divalent cations on polysaccharide membrane fouling

Divalent cations and organics are two main types of foulants in feed water to the membrane processes and cations often bind to organic foulants which significantly affects fouling. Extensive efforts have been devoted to exploring the influence of single cation on organic fouling while there are diverse cations in the feed. Thus, it is essential to understand the coupling influence of different divalent cations on fouling development. In this study, sodium alginate was chosen as a model foulant to investigate the effect of different Ca2+/Mg2+ ratios on its fouling behavior. Filtration performances, the quantity and morphology of transparent exopolymer particles (TEP) derived from alginate were analyzed along with the morphology and structure of corresponding fouling layers. TEP measurements reveal that the Ca2+/Mg2+ ratio is crucial in the characteristics of TEP, which further determines the structure of the fouling layer. At a low Ca2+/Mg2+ ratio, the TEP are amorphous-TEP (a-TEP) with small and unconsolidated structure which forms a fouling layer under pressure with high hydraulic resistance. In contrast, interactions between polysaccharides at high Ca2+/Mg2+ ratio are much stronger and result in large and tight particulate-TEP (p-TEP). Such p-TEP lead to a fouling layer with high porosity and low hydraulic resistance. The role of Mg2+ in polysaccharide fouling is more important than expected because it promotes the formation of a-TEP, which show a high fouling potential at high levels because more dense gel layer forms. This study suggests that the morphology and structure of TEP play crucial roles in polysaccharide fouling propensities. A-TEP at high levels needs more attention to ensure the successful operation of membrane systems in future work.

A hydrogel reservoir as a self-contained nucleus pulposus cell delivery vehicle for immunoregulation and repair of degenerated intervertebral disc

The strategies for modulating the local inflammatory microenvironment to inhibit intervertebral disc degeneration (IVDD) have garnered significant interest in recent years. In this study, we developed a "self-contained" injectable hydrogel capable of storing Mg2+ while carrying nucleus pulposus (NP) cells, with the aim of inhibiting IVDD through immunoregulation. The hydrogel consists of sodium alginate (SA), poly(N-isopropylacrylamide) (PNIPAAm), silicate ceramics (SC), and NP cells. When injected into the NP site, PNIPAAm gelates instantly under body temperature, forming an interpenetrating network (IPN) hydrogel with SA. Ca2+ released from the SC can crosslink the SA in situ, forming a SA/PNIPAAm hydrogel with an interpenetrating network (IPN) encapsulating the NP cells. Moreover, inside the hydrogel, Mg2+ released from SC are effectively encapsulated and maintained at a desirable concentration. These Mg2+ facilitates the local cell matrix synthesis and promotes immunomodulation (upregulating M2 / downregulating M1 macrophage polarization), thus inhibiting the IVDD progression. The proposed hydrogel has biocompatibility and is shown to enhance the expression of collagen II (COL II) and aggrecan. The potential of the injectable hydrogel in IVD repair has also been successfully demonstrated by in vivo studies. Statement of significance•A unique injectable hydrogel consisting of sodium alginate (SA), poly(N-isopropylacrylamide) (PNIPAAm), silicate ceramics (SC) and nucleus pulposus cells, has been created for intervertebral disc repair applications.•This is the first “self-contained” cell delivery system capable of releasing and subsequently storing Mg2+ in the hydrogel reservoir for localized treatment.•The role of Mg2+ in regulating the macrophage polarity transformation (from pro-inflammatory M1 to anti-inflammatory M2 phenotype) has been unveiled in the context of intervertebral disc repair.

Physiological importance and role of Mg2+ in improving bacterial resistance to cesium.

Cesium (Cs) is an alkali metal with radioactive isotopes such as 137Cs and 134Cs. 137Cs, a product of uranium fission, has garnered attention as a radioactive contaminant. Radioactive contamination remediation using microorganisms has been the focus of numerous studies. We investigated the mechanism underlying Cs+ resistance in Microbacterium sp. TS-1 and other representative microorganisms, including Bacillus subtilis. The addition of Mg2+ effectively improved the Cs+ resistance of these microorganisms. When exposed to high concentrations of Cs+, the ribosomes of Cs+-sensitive mutants of TS-1 collapsed. Growth inhibition of B. subtilis in a high-concentration Cs+ environment was because of a drastic decrease in the intracellular potassium ion concentration and not the destabilization of the ribosomal complex. This is the first study demonstrating that the toxic effect of Cs+ on bacterial cells differs based on the presence of a Cs+ efflux mechanism. These results will aid in utilizing high-concentration Cs+-resistant microorganisms for radioactive contamination remediation in the future.

Magnesium in aging and aging-related disease

Magnesium (Mg2+) is an essential divalent cation in human body. Its balance is tightly controlled via a balanced interplay among intestinal absorption, storage, and renal excretion, involving multiple transporters across cell membrane that regulate Mg2+ influx and efflux. Mg2+ is involved in a variety of physiological and pathological processes such as enzymatic reactions, energy metabolism, cell proliferation, apoptosis, oxidative stress, and inflammation. In particular, Mg2+ contributes to the molecular hallmarks of aging. Emerging evidence demonstrates that altered Mg2+ status has been associated with many aging-related diseases, including cancer, cardiovascular disease, neurodegenerative disease, musculoskeletal function, metabolic syndrome, and COVID-19. In this review, we focus on Mg2+ and its association with molecular hallmarks of aging. We also summarize recent findings supporting an important role of Mg2+ in aging-related disease including the COVID-19 pandemic.

Effect of Mg2+ additives on Nieuwland catalyst: The role of the second metal ionic radius

AbstractIn the production of chloroprene rubber, acetylene dimerization over the Nieuwland catalyst is an important step. The addition of Mg2+ to the Nieuwland catalyst improves the acetylene conversion and the selectivity toward vinyl acetylene. In this study, active component crystal structure, the role of Mg2+ in the Nieuwland catalyst, the reason for the catalyst deactivation, and the reaction mechanism were analyzed by different characterization techniques. The results indicate that the main reason for the Nieuwland catalyst deactivation is the loss of Cu2+. The addition of Mg2+ will increase the exposure of active sites, reduce the residence time of acetylene in the catalyst, and inhibit the reduction of Cu2+, thereby improving the catalytic performance and stability of the catalyst.

Amorphous calcium magnesium phosphate nanocomposites with superior osteogenic activity for bone regeneration.

The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules is considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple co-precipitation strategy. The physiochemical property of ACMP/SIM was explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high-performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and , when it is immersed in SBF at 37°C, and a phase transformation occurred during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

Role of Mg2+ substitution on viscosity and thermal conductivity of nickel ferrite based magnetic fluids

The present investigation shows the viscosity and thermal conductivity of Mg2+ substituted nickel ferrite based magnetic fluids of different chemical compositions (Ni1-xMgxFe2O4). The nanoparticles were synthesized using a simple and cost-effective co-precipitation method. The XRD result shows the formation of a cubic spinel structure. SEM analysis confirmed the size of the nanoparticles ranges between 1 µm and 500 nm. The Experimental results show that the viscosity of magnetic fluids of two different volume fractions decreases for the rise in temperature and for the increase in rotations per minute (RPM). The results on thermal conductivity of two different volume fractions of Ni1-xMgxFe2O4 based magnetic fluids exhibit enhanced thermal conductivity than the carrier fluid (transformer oil). The thermal conductivity results were compared with Maxwell’s theoretical prediction and experimental models for confirmation.

'Magnesium'-the master cation-as a drug-possibilities and evidences.

Magnesium (Mg2+) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions. Magnesium (Mg2+) can regulate several cations, including sodium, potassium, and calcium; it consequently maintains physiological functions like impulse conduction, blood pressure, heart rhythm, and muscle contraction. But, it doesn’t get much attention in account with its functions, making it a “Forgotten cation”. Like other cations, maintenance of the normal physiological level of Mg2+ is important. Its deficiency is associated with various diseases, which point out to the importance of Mg2+ as a drug. The roles of Mg2+ such as natural calcium antagonist, glutamate NMDA receptor blocker, vasodilator, antioxidant and anti-inflammatory agent are responsible for its therapeutic benefits. Various salts of Mg2+ are currently in clinical use, but their application is limited. This review collates all the possible mechanisms behind the behavior of magnesium as a drug at different disease conditions with clinical shreds of evidence.

Current Understandings on Magnesium Deficiency and Future Outlooks for Sustainable Agriculture.

The productivity of agricultural produce is fairly dependent on the availability of nutrients and efficient use. Magnesium (Mg2+) is an essential macronutrient of living cells and is the second most prevalent free divalent cation in plants. Mg2+ plays a role in several physiological processes that support plant growth and development. However, it has been largely forgotten in fertilization management strategies to increase crop production, which leads to severe reductions in plant growth and yield. In this review, we discuss how the Mg2+ shortage induces several responses in plants at different levels: morphological, physiological, biochemical and molecular. Additionally, the Mg2+ uptake and transport mechanisms in different cellular organelles and the role of Mg2+ transporters in regulating Mg2+ homeostasis are also discussed. Overall, in this review, we critically summarize the available information about the responses of Mg deficiency on plant growth and development, which would facilitate plant scientists to create Mg2+-deficiency-resilient crops through agronomic and genetic biofortification.

Role of Mg2+ and In3+ substitution on magnetic, magnetostrictive and dielectric properties of NiFe2O4 ceramics derived from nanopowders.

The effect of Mg2+ and In3+ substitution on the structural, magnetic, magnetostrictive and dielectric properties of NiFe2O4 samples derived through sintering of nanocrystalline ceramic powders is investigated. Namely, NiFe2O4, NiMg0.2Fe1.8O4 and NiIn0.2Fe1.8O4 nanopowders were synthesized by a tartrate-gel route followed by calcination at 500 °C, pelletization and sintering at 1200 °C for 2 h. The average particle size was found to decrease from ∼13 nm (for NiFe2O4) to ∼9 nm and ∼7 nm for as-synthesized Mg2+ and In3+ substituted NiFe2O4 samples (after calcination), respectively. However, after sintering a better grain growth occurs for the In3+ substituted sample, as confirmed through the microscopy and dielectric results. Due to the replacement of smaller Fe3+ cations by larger In3+ and Mg2+ cations at the tetrahedral (Td) and octahedral (Oh) interstitial positions, respectively, in the spinel structure of NiFe2O4, the lattice parameters increase in both the cases. The Td site occupation of In3+ leads to higher magnetization for the NiIn0.2Fe1.8O4 sample, but Oh site occupation of Mg2+ leads to lower magnetization for the NiMg0.2Fe1.8O4 sample, in comparison to the pure NiFe2O4 sample. Furthermore, the Curie temperatures (TC) and magnetocrystalline anisotropy constants (K1) for both the samples are considerably lower than the parent compound, with all the parameters being the lowest for the In3+ substituted sample because the Td occupation of non-magnetic In3+ drastically decreases the A-O-B magnetic superexchange interactions. The above alteration to the magnetic interactions alters the magnitude of maximum magnetostriction (λmax), which is explained based on the occupation of the Mg2+ and In3+ cations in our samples. The obtained magnetostriction properties of our samples are very useful for magnetostriction based sensor application.

Cations stress on low-grade nickel sulfide ore oxidation leaching

The effects of cations stress of magnesium ion and sodium ion on the low-grade nickel sulfide ore oxidative leaching in simulated sulfuric acid solutions were investigated. This study was performed in two courses, including the effect of the cations on the valuable metals leaching efficiencies of the nickel ore and its influences on the electrochemical oxidation behavior of the nickel ore. The leaching results present that parts of magnesium-containing gangues and ferrous sulfide are preferentially dissolved into lixivium, and the leaching efficiencies of Ni and Cu decreased much related to the leached concentrations of Mg2+ increased. The results of electrochemical measurements show that the oxidation leaching of the low-grade nickel sulfide ore is controlled by the intermediates oxidative diffusion. Mg2+, as well as Na+, affects the transformations of the Fe3+/Fe2+ couple and sulfur-containing species, and those cations are apt to be attracted by the anions and directionally adhere to the negative active site of the metal sulfide surface, causing an increase in the electrochemical activities, which facilitates the electron transfer between the ore and leaching mediums. By comparative study of the role of Mg2+ and Na+, it is found that Mg2+ negatively affects the oxidative diffusion of the intermediates through promoting the generation of a compact film, which lowers the metals leached efficiencies, and the unfavorable effect of Na+ tends to be the coupled effect of the leached Mg2+ and Fe3+.

Mechanism of Nucleotidyltransfer Reaction and Role of Mg2+ Ion in Sugar Nucleotidyltransferases

Sugar nucleotidyl transferases (SNTs) catalyze nucleotidyltransfer reactions to form sugar-nucleotides and pyrophosphate in the presence of two Mg2+ ions (Mg2+A and Mg2+B). We unveil the mechanism and free energetics of nucleotidyl transfer reaction in an SNT called GlmU through hybrid quantum mechanics-molecular mechanics molecular dynamics simulations and free energy calculations. The study identifies the roles of the active site residues and the Mg2+ ions in catalyzing the reaction. Of great significance, we are able to compare the free energy barrier for the reaction with that for the Mg2+-assisted release of the product (i.e., pyrophosphate) into the solution, shedding light on the general mechanistic and kinetic aspects of catalysis by SNTs.

Confluence of theory and experiment reveals the catalytic mechanism of the Varkud satellite ribozyme

The Varkud Satellite (VS) ribozyme catalyzes site-specific RNA cleavage and ligation, and serves as an important model system to understand RNA catalysis. Here we combine stereospecific phosphorothioate substitution, precision nucleobase mutation and linear free energy relationship measurements with molecular dynamics, molecular solvation theory, and ab initio quantum mechanical/molecular mechanical free energy simulations to gain insight into catalysis. Through this confluence of theory and experiment, we unify the existing body of structural and functional data to unveil the catalytic mechanism in unprecedented detail, including the degree of proton transfers in the transition state. Further, we provide evidence for a critical Mg2+ ion in the active site that interacts with the scissile phosphate and anchors the general base guanine in position for nucleophile activation. This novel role for Mg2+ adds to the diversity of known catalytic RNA strategies and unifies functional features observed in the VS, hairpin, and hammerhead ribozyme classes.

The Role of Mg2 and BSA Langmuir Monolayers in Controlling Polymorph and Morphology of CaCO3 Crystal

Mg2+ and bovine serum albumin (BSA) Langmuir monolayers were used as effective crystal nucleation and growth modifiers and template to control the crystallization of CaCO3. The polymorph and morphology of crystals were characterized using scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results demonstrated that various morphologies such as abacus-bead-like particles, spherical-shaped particles, wood block-like particles, pignut-shell-like particles and the rolling pole shaped particles produced at the interface of film/solution. With the increasing of the molar ratio of Mg2+ to Ca2+, the polymorph of calcium carbonate obtained undergoes an evolvement from calcite to vaterite and aragonite. The ability of Mg2+ to induce the formation of aragonite was enhanced as the molar ratio of Mg2+ to Ca2+ increased. When the molar ratio reached 3, the crystals obtained were all aragonite. In the systems of Mg2+-BSA Langmuir monolayers, the presence of Mg2+ was helpful for the formation of aragonite. The possible formation mechanisms of CaCO3 in different systems were discussed in the paper.

Characterization and modeling on the role of Mg2+ in seawater blended Portland cement systems

In this study, the effect of Mg2+ on early hydration of Portland cement is addressed. Heat flow calorimetry and ICP-OES are employed to characterize the cement hydration at early age. XRD, TG-DSC are utilized to demonstrate the changes of phase composition during early age. SEM-EDS and 27Al MAS NMR are used to reveal phase transformation of aluminum related hydration products. The results show that the induction period of cement is prolonged after Mg2+ incorporation, resulting in decreased dissolution of clinker minerals. The effect of Mg2+ on acceleration period depends on its concentration. Mg2+ hinders the formation of Ca(OH)2 and transformation from AFt to AFm and TAH.

Conformational resolution of nucleotide cycling and effector interactions for multiple small GTPases determined in parallel

Small GTPases alternatively bind GDP/GTP guanine nucleotides to gate signaling pathways that direct most cellular processes. Numerous GTPases are implicated in oncogenesis, particularly the three RAS isoforms HRAS, KRAS, and NRAS and the RHO family GTPase RAC1. Signaling networks comprising small GTPases are highly connected, and there is some evidence of direct biochemical cross-talk between their functional G-domains. The activation potential of a given GTPase is contingent on a codependent interaction with the nucleotide and a Mg2+ ion, which bind to individual variants with distinct affinities coordinated by residues in the GTPase nucleotide-binding pocket. Here, we utilized a selective-labeling strategy coupled with real-time NMR spectroscopy to monitor nucleotide exchange, GTP hydrolysis, and effector interactions of multiple small GTPases in a single complex system. We provide insight into nucleotide preference and the role of Mg2+ in activating both WT and oncogenic mutant enzymes. Multiplexing revealed guanine nucleotide exchange factor (GEF), GTPase-activating protein (GAP), and effector-binding specificities in mixtures of GTPases and resolved that the three related RAS isoforms are biochemically equivalent. This work establishes that direct quantitation of the nucleotide-bound conformation is required to accurately determine an activation potential for any given GTPase, as small GTPases such as RAS-like proto-oncogene A (RALA) or the G12C mutant of KRAS display fast exchange kinetics but have a high affinity for GDP. Furthermore, we propose that the G-domains of small GTPases behave autonomously in solution and that nucleotide cycling proceeds independently of protein concentration but is highly impacted by Mg2+ abundance.