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Methods in Enzymology 2024Magnesium ions (Mg) are crucial in class II terpene cyclases that utilize substrates with diphosphate groups. Interestingly, these enzymes catalyze reactions without...
Magnesium ions (Mg) are crucial in class II terpene cyclases that utilize substrates with diphosphate groups. Interestingly, these enzymes catalyze reactions without cleaving the diphosphate group, instead initiating the reaction through protonation. In our recent research, we discovered a novel class II sesquiterpene cyclase in Streptomyces showdoensis. Notably, we determined its crystal structure and identified Mg within its active site. This finding has shed light on the previously elusive question of Mg binding in class II terpene cyclases. In this chapter, we outline our methods for discovering this novel enzyme, including steps for its purification, crystallization, and kinetic analysis.
Topics: Magnesium; Sesquiterpenes; Streptomyces; Binding Sites; Kinetics; Bacterial Proteins; Catalytic Domain; Crystallography, X-Ray; Structure-Activity Relationship; Crystallization; Carbon-Carbon Lyases
PubMed: 38942506
DOI: 10.1016/bs.mie.2024.02.018 -
The Journal of Neuroscience : the... Jun 2024NMDA-type glutamate receptors (NMDARs) are widely recognized as master regulators of synaptic plasticity, most notably for driving long-term changes in synapse size and...
NMDA-type glutamate receptors (NMDARs) are widely recognized as master regulators of synaptic plasticity, most notably for driving long-term changes in synapse size and strength that support learning. NMDARs are unique among neurotransmitter receptors in that they require binding of both neurotransmitter (glutamate) and co-agonist (e.g. d-serine) to open the receptor channel, which leads to the influx of calcium ions that drive synaptic plasticity. Over the past decade, evidence has accumulated that NMDARs also support synaptic plasticity via ion flux-independent (non-ionotropic) signaling upon the binding of glutamate in the absence of co-agonist, although conflicting results have led to significant controversy. Here, we hypothesized that a major source of contradictory results can be attributed to variable occupancy of the co-agonist binding site under different experimental conditions. To test this hypothesis, we manipulated co-agonist availability in acute hippocampal slices from mice of both sexes. We found that enzymatic scavenging of endogenous co-agonists enhanced the magnitude of LTD induced by non-ionotropic NMDAR signaling in the presence of the NMDAR pore blocker, MK801. Conversely, a saturating concentration of d-serine completely inhibited both LTD and spine shrinkage induced by glutamate binding in the presence of MK801. Using a FRET-based assay in cultured neurons, we further found that d-serine completely blocked NMDA-induced conformational movements of the GluN1 cytoplasmic domains in the presence of MK801. Our results support a model in which d-serine inhibits ion flux-independent NMDAR signaling and plasticity, and thus d-serine availability could serve to modulate NMDAR signaling even when the NMDAR is blocked by magnesium. NMDARs are glutamate-gated cation channels that are key regulators of neurodevelopment and synaptic plasticity and unique in their requirement for binding of a co-agonist (e.g. d-serine) in order for the channel to open. NMDARs have been found to drive synaptic plasticity via non-ionotropic (ion flux-independent) signaling upon the binding of glutamate in the absence of co-agonist, though conflicting results have led to controversy. Here, we found that d-serine inhibits non-ionotropic NMDAR-mediated LTD and LTD-associated spine shrinkage. Thus, a major source of the contradictory findings might be attributed to experimental variability in d-serine availability. In addition, the developmental regulation of d-serine levels suggests a role for non-ionotropic NMDAR plasticity during critical periods of plasticity.
PubMed: 38942470
DOI: 10.1523/JNEUROSCI.0140-24.2024 -
The American Journal of Medicine Jun 2024African-Americans and Hispanic Americans experience a higher incidence and prevalence of dementia than white Americans while also experiencing more environmental,... (Review)
Review
African-Americans and Hispanic Americans experience a higher incidence and prevalence of dementia than white Americans while also experiencing more environmental, metabolic and nutritional factors potentially promoting such disparities. Greater exposure to air, water and soil pollutants including toxic metals associated with neurodegeneration accrue to both minorities, as does worse dental care than whites exposing them to periodontitis raising dementia risk. Hispanic Americans experience greater occupational exposure to herbicides and pesticides develop more non-alcoholic fatty liver disease (NAFLD) predisposing to dementia. African-Americans have a greater likelihood of both Vitamin D deficiency and magnesium deficiency increasing neuroinflammation and dementia risk. Both have greater air pollution exposure, a known dementia risk. Nutritional changes including greater nut consumption and reduced sugar drink consumption, improved dental care, and reduced toxicant exposure may help reduce this higher risk of dementia among African Americans and Hispanic Americans.
PubMed: 38942346
DOI: 10.1016/j.amjmed.2024.06.023 -
Science Advances Jun 2024The recent discovery of the large piezoelectric response of Pb(MgNb)O-PbTiO (PMN-PT) ceramics induced by samarium doping has provided a substantially improved...
The recent discovery of the large piezoelectric response of Pb(MgNb)O-PbTiO (PMN-PT) ceramics induced by samarium doping has provided a substantially improved functionality to the group of lead-based relaxor-ferroelectric materials. Different mechanisms have been so far proposed for the large piezoelectricity; however, the explanations are contradictory and focused on a unified description. Here, we use nonlinear harmonic piezoelectric measurements combined with multiscale structural analysis to clarify the origins of the ultrahigh piezoelectric response of samarium-doped PMN-PT. Our methodological approach allowed us to separate the multiple piezoelectric contributions, revealing their quantitative role in the total response. The results show that the ultrahigh piezoelectricity cannot be attributed to a single mechanism but is rather a complex combination of different contributions originating from the multiple effects of samarium doping on the long- and short-range structure of PMN-PT. The study offers a baseline for future engineering of the key material parameters affecting the large piezoelectric response of relaxor-ferroelectric ceramics.
PubMed: 38941470
DOI: 10.1126/sciadv.adp0895 -
Scientific Reports Jun 2024This study investigates using magnesium foliar spray to enhance mint plants' growth and physiological performance under cadmium toxicity. It examines the effects of...
This study investigates using magnesium foliar spray to enhance mint plants' growth and physiological performance under cadmium toxicity. It examines the effects of foliar application of magnesium oxide (40 mg L), in both nano and bulk forms, on mint plants exposed to cadmium stress (60 mg kg soil). Cadmium stress reduced root growth and activity, plant biomass (32%), leaf hydration (19%), chlorophyll levels (27%), magnesium content (51%), and essential oil yield (35%), while increasing oxidative and osmotic stress in leaf tissues. Foliar application of magnesium increased root growth (32%), plant biomass, essential oil production (17%), leaf area (24%), chlorophyll content (10%), soluble sugar synthesis (33%), and antioxidant enzyme activity, and reduced lipid peroxidation and osmotic stress. Although the nano form of magnesium enhanced magnesium absorption, its impact on growth and physiological performance was not significantly different from the bulk form. Therefore, foliar application of both forms improves plants' ability to withstand cadmium toxicity. However, the study is limited by its focus on a single plant species and specific environmental conditions, which may affect the generalizability of the results. The long-term sustainability of such treatments could provide a more comprehensive understanding of magnesium's role in mitigating heavy metal stress in plants.
Topics: Magnesium Oxide; Cadmium; Mentha; Plant Leaves; Stress, Physiological; Chlorophyll; Lipid Peroxidation; Plant Roots; Oxidative Stress; Antioxidants; Magnesium; Biomass
PubMed: 38937645
DOI: 10.1038/s41598-024-65853-0 -
AAPS PharmSciTech Jun 2024Only few excipients are known to be suitable as pelletization aids. In this study, the potential use of croscarmellose sodium (CCS) as pelletization aid was...
Only few excipients are known to be suitable as pelletization aids. In this study, the potential use of croscarmellose sodium (CCS) as pelletization aid was investigated. Furthermore, the impact of cations on extrusion-spheronization (ES) of CCS was studied and different grades of CCS were tested. The influence of different cations on the swelling of CCS was investigated by laser diffraction. Mixtures of CCS with lactose monohydrate as filler with or without the inclusion of different cations were produced. The mixtures were investigated by mixer torque rheometry and consequently extruded and spheronized. Resulting pellets were analyzed by dynamic image analysis. In addition, mixtures of different CCS grades with dibasic calcium phosphate anhydrous (DP) and a mixture with praziquantel (PZQ) as filler were investigated. Calcium and magnesium cations caused a decrease of the swelling of CCS and influenced the use of CCS as pelletization aid since they needed to be included for successful ES. Aluminum, however, led to an aggregation of the CCS particles and to failure of extrusion. The inclusion of cations decreased the uptake of water by the mixtures which also reduced the liquid-to-solid-ratio (L/S) for successful ES. This was shown to be dependent on the amount of divalent cations in the mixture. With DP or PZQ as filler, no addition of cations was necessary for a successful production of pellets, however the optimal L/S for ES was dependent on the CCS grade used. In conclusion, CCS can be used as a pelletization aid.
Topics: Excipients; Particle Size; Drug Compounding; Calcium Phosphates; Lactose; Chemistry, Pharmaceutical; Cations; Praziquantel; Magnesium
PubMed: 38937406
DOI: 10.1208/s12249-024-02864-0 -
Environmental Science and Pollution... Jun 2024Red mud is a highly alkaline solid waste discharged from the alumina industry, and its high sodium content is the key factor limiting its wide utilization. Therefore,...
Red mud is a highly alkaline solid waste discharged from the alumina industry, and its high sodium content is the key factor limiting its wide utilization. Therefore, effective control of the "frosting" phenomenon during the application of red mud has received significant attention. In this study, the changes of particle size, phase, morphology, and pore size of red mud after sodium removal with different amounts of citric acid pretreatment were investigated. The single-factor experiment shows that the Na leaching rate is 86.33% under a citric acid dosage of 15%, liquid-to-solid ratio of 7 mL/g, leaching temperature of 80 °C, stirring speed of 300 rpm, and leaching time of 10 min. The leachate is characterized through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Brunauer-Emmett-Teller (BET) surface area analysis. The results reveal that Na mainly exists in a combined state in the form of cancrinite. With the increase of citric acid dosage, red mud agglomerates, calcite, and cancrinite are dissolved, and new phases such as calcium oxalate and magnesium aluminum hydroxide are formed. The specific surface area, pore volume, and pore diameter show irregular changes with the increase in the citric acid dosage. Citric acid pretreatment can effectively reduce the sodium content in red mud, the treatment cost of leaching solution is low, and the leaching residue is neutral, which is helpful to promote the practical application of red mud.
PubMed: 38937355
DOI: 10.1007/s11356-024-33850-5 -
International Journal of Biological... Jun 2024Polyether-ether-ketone (PEEK) is clinically used as a bio-implant for the healing of skeletal defects. However, the osseointegration of clinical-sized bone grafts...
Polyether-ether-ketone (PEEK) is clinically used as a bio-implant for the healing of skeletal defects. However, the osseointegration of clinical-sized bone grafts remains limited. In this study, surface-porous PEEK was created by using a sulfonation method and a metal-polysaccharide complex MgCS was introduced on the surface of sulfonated PEEK to form MgCS@SPEEK. The as-prepared MgCS@SPEEK was found to have a porous surface with good hydrophilicity and bioactivity. This was followed by an investigation into whether MgCS loaded onto sulfonated PEEK surfaces could promote osseointegration and angiogenesis. The in vitro results showed that MgCS@SPEEK had a positive effect on reducing the expression levels of inflammatory genes and promoting osteogenesis and angiogenesis-related genes expression levels. Furthermore, porous MgCS@SPEEK was implanted in critical-sized rat tibiae defects for in vivo evaluation of osseointegration. The microcomputed tomography evaluation results revealed substantial bone formation at 4 and 8 weeks. Collectively, these findings indicate that MgCS@SPEEK could provide improved osseointegration and an attractive strategy for orthopedic applications.
PubMed: 38936580
DOI: 10.1016/j.ijbiomac.2024.133435 -
ACS Applied Materials & Interfaces Jun 2024Mechanoluminescence (ML) is the nonthermal luminescence generated in the process of force-to-light conversion, which has broad prospects in stress sensing, wearable...
Mechanoluminescence (ML) is the nonthermal luminescence generated in the process of force-to-light conversion, which has broad prospects in stress sensing, wearable devices, biomechanics, and multiple information anticounterfeiting. Multivalence emitter ions utilize their own self-reduction process to realize multiband ML without introducing another dopant, such as Eu/Eu, Sm/Sm, and Mn/Mn. However, self-reduction-induced ML in bismuth-activated materials has rarely been reported so far. In this work, a novel visible-to-near-infrared (vis-NIR) ML induced by the self-reduction of Bi to Bi in the spinel-type compound (MgGaO) is reported. The photoluminescence (PL) spectra, PL excitation (PLE) spectra, and PL lifetime curves demonstrate that Bi/Bi ions are the main luminescence centers. Notably, the possible self-reduction model is proposed, where a magnesium vacancy (V) is considered as the driving force for the self-reduction of Bi to Bi. Furthermore, an oxygen vacancy (V) is confirmed by electron paramagnetic resonance (EPR) spectroscopy. Combined with thermoluminescence (TL) glow curves and ML spectra, a plausible trap-controlled ML mechanism is illustrated, where electron-hole (V/V) pairs play a significant role in capturing electrons and holes. It is worth noting that the proof-of-concept dual-mode electronic signature application is implemented based on the flexible ML film, which improves the capabilities of signature anticounterfeiting for high-level security applications. Besides, multistimulus-responsive luminescence behaviors of the ML film are realized under the excitation of a 254 nm UV lamp, thermal disturbance, 980 nm laser, and mechanical stimuli. In general, this study provides new insights into designing vis-NIR ML materials toward wider application possibilities.
PubMed: 38935739
DOI: 10.1021/acsami.4c04499 -
Annals of the American Thoracic Society Jun 2024Guidelines recommend systemic corticosteroids and inhaled beta-agonists for patients with severe asthma exacerbation admitted to intensive care units (ICUs). The...
RATIONALE
Guidelines recommend systemic corticosteroids and inhaled beta-agonists for patients with severe asthma exacerbation admitted to intensive care units (ICUs). The benefits and utilization of adjunct treatments after guideline recommended first-line treatments have been initiated are unclear.
METHODS
Using the Premier Inc. PINC AI multicenter database (2016-2022), we sought to explore the use of adjunct interventions (medications [e.g., magnesium, leukotriene inhibitors, terbutaline, heliox]; and procedures [e.g., invasive and non-invasive mechanical ventilation]) for adult patients admitted to United States (US) ICUs with acute asthma exacerbations. We used hierarchical generalized linear models to calculate risk-adjusted rates of adjunct interventions and quantified between-hospital variation in adjunct interventions using the intraclass correlation coefficient (ICC - higher values correspond to higher between hospital variation). We then used K-means clustering to identify groups of hospitals with similar risk-adjusted practice profiles of all adjunct treatments and examined associations between identified hospital clusters and patient outcomes.
RESULTS
We identified 62,392 patients from 961 hospitals for inclusion. Adjunct interventions with the highest between hospital variation after risk-adjustment were heliox (ICC 91%), inhaled steroids (ICC 23%), invasive mechanical ventilation (ICC 21%), terbutaline (ICC 22%), paralytics (ICC 16%), and non-invasive ventilation (ICC 15%). K-means clustering identified two distinct hospital clusters: patients admitted to cluster 1 hospitals (399 hospitals) had higher risk-adjusted rates of non-invasive ventilation (51% vs 33%) compared to patients admitted to cluster 2 hospitals (234 hospitals) which had higher risk-adjusted rates of invasive mechanical ventilation (63% vs 30%). Cluster 2 was associated with fewer hospital free days (beta -0.75 days, CI -0.95, -0.55 days) and increased in-hospital mortality (aOR 1.28, CI 1.17, 1.40).
CONCLUSIONS
The use of adjunct interventions for patients with severe asthma exacerbations vary widely across US hospitals; however, hospitals generally fall into two clusters differentiated primarily by the use of invasive or non-invasive mechanical ventilation. Our results help to inform usual care arms of future comparative effectiveness studies and efforts to standardize asthma practice.
PubMed: 38935672
DOI: 10.1513/AnnalsATS.202401-085OC