Project description:Glyphosate is an important and widely used herbicide, its environmental behaviour being of scientific and public interest. Computational models of clay minerals and their interactions with small organic molecules are valuable in studying adsorption processes at an atomistic resolution. We analysed the adsorption process of glyphosate on kaolinite, a clay mineral with a high abundance in several types of soils (e.g., of subtropical or tropical origin), in terms of the adsorption strength. The molecular interactions are characterized by monitoring the occurrence of hydrogen bonds, the orientation of the molecular dipole relative to the interface and the interaction energy. Two different ionic forms of glyphosate were considered: neutral and anionic (-1). It was shown that the main mechanism of the binding of both glyphosate forms to the aluminol surface of kaolinite is through multiple hydrogen bonds. The standard free energy of adsorption of neutral glyphosate from water solution to the basal octahedral surface of kaolinite was computed at -5 kJ mol-1, whereas for the anionic form this quantity amounted to -14 kJ mol-1. Our finding showed that kaolinite has an important contribution to overall adsorption capacity of soils for glyphosate, specifically in its anionic form.HighlightsThe adsorption free energy of glyphosate on a kaolinite surface is quantifiedInteractions are computed by quantum mechanics and by classical force fieldMolecular interactions are characterized in terms of hydrogen bonds and orientationsThe effect of polarization of the medium on the calculations is analysed.
Project description:A kinetic mechanism and the accompanying mathematical framework are presented for base-mediated thiol-Michael photopolymerization kinetics involving a photobase generator. Here, model kinetic predictions demonstrate excellent agreement with a representative experimental system composed of 2-(2-nitrophenyl)propyloxycarbonyl-1,1,3,3-tetramethylguanidine (NPPOC-TMG) as a photobase generator that is used to initiate thiol-vinyl sulfone Michael addition reactions and polymerizations. Modeling equations derived from a basic mechanistic scheme indicate overall polymerization rates that follow a pseudo-first-order kinetic process in the base and coreactant concentrations, controlled by the ratio of the propagation to chain-transfer kinetic parameters (kp/kCT) which is dictated by the rate-limiting step and controls the time necessary to reach gelation. Gelation occurs earlier as the kp/kCT ratio reaches a critical value, wherefrom gel times become nearly independent of kp/kCT. The theoretical approach allowed determining the effect of induction time on the reaction kinetics due to initial acid-base neutralization for the photogenerated base caused by the presence of protic contaminants. Such inhibition kinetics may be challenging for reaction systems that require high curing rates but are relevant for chemical systems that need to remain kinetically dormant until activated although at the ultimate cost of lower polymerization rates. The pure step-growth character of this living polymerization and the exhibited kinetics provide unique potential for extended dark-cure reactions and uniform material properties. The general kinetic model is applicable to photobase initiators where photolysis follows a unimolecular cleavage process releasing a strong base catalyst without cogeneration of intermediate radical species.
Project description:Kidney fibrosis, characterized by excessive extracellular matrix (ECM) deposition, is a progressive disease that, despite affecting 10% of the population, lacks specific treatments and suitable biomarkers. Aimed at unraveling disease mechanisms and identifying potential therapeutic targets, this study presents a comprehensive, time-resolved multi-omics analysis of kidney fibrosis using an in vitro model system based on human kidney PDGFRβ+ mesenchymal cells. Using computational network modeling we integrated transcriptomics, proteomics, phosphoproteomics, and secretomics with imaging of the extracellular matrix (ECM). We quantified over 14,000 biomolecules across seven time points following TGF-β stimulation, revealing distinct temporal patterns in the expression and activity of known and potential novel renal fibrosis markers and modulators. The resulting time-resolved multi-omic network models allowed us to propose mechanisms related to fibrosis progression through early transcriptional reprogramming. Using siRNA knockdowns and phenotypic assays, we validated predictions and elucidated regulatory mechanisms underlying kidney fibrosis. Notably, we demonstrate that several early-activated transcription factors, including FLI1 and E2F1, act as negative regulators of collagen deposition and propose underlying molecular mechanisms. This work advances our understanding of the pathogenesis of kidney fibrosis and provides a valuable resource for the organ fibrosis research community.
Project description:The presence of volatile organic compounds in groundwater is a major concern when it is used as a drinking water source because many of these compounds can adversely affect human health. This work reports on the preparation and characterization of white and red Brazilian São Simão's kaolinite-TiO2 nanocomposites and their use as catalysts in the photochemical degradation of toluene, a significant volatile organic compound. The nanocomposites were prepared by a sol-gel procedure, using titanium bis(triethanolaminate)diisopropoxide as a precursor. Thermal treatments of the nanocomposites led to different polymorphic titania phases, while the clay changed from kaolinite to metakaolinite. This structural evolution strongly affected the photocatalytic degradation behavior-all the solids efficiently degraded toluene and the solid calcined at 400 °C, formed by kaolinite and anatase, showed the best behavior (90% degradation). On extending the photochemical treatment up to 48 h, high mineralization levels were reached. The advantage of photodegradation using the nanocomposites was confirmed by comparing the results from isolated components (titanium dioxide and kaolinite) to observe that the nanocomposites displayed fundamental importance to the photodegradation pathways of toluene.
Project description:Cold-tolerant, neurotoxigenic, endospore forming Clostridium (C.) botulinum type E belongs to the non-proteolytic physiological C. botulinum group II, is primarily associated with aquatic environments, and presents a safety risk for seafood. High pressure thermal (HPT) processing exploiting the synergistic effect of pressure and temperature can be used to inactivate bacterial endospores. We investigated the inactivation of C. botulinum type E spores by (near) isothermal HPT treatments at 300-1200 MPa at 30-75°C for 1 s to 10 min. The occurrence of heat and lysozyme susceptible spore fractions after such treatments was determined. The experimental data were modeled to obtain kinetic parameters and represented graphically by isoeffect lines. In contrast to findings for spores of other species and within the range of treatment parameters applied, zones of spore stabilization (lower inactivation than heat treatments alone), large heat susceptible (HPT-induced germinated) or lysozyme-dependently germinable (damaged coat layer) spore fractions were not detected. Inactivation followed first order kinetics. Dipicolinic acid release kinetics allowed for insights into possible inactivation mechanisms suggesting a (poorly effective) physiologic-like (similar to nutrient-induced) germination at ≤450 MPa/≤45°C and non-physiological germination at >500 MPa/>60-70°C. Results of this study support the existence of some commonalities in the HPT inactivation mechanism of C. botulinum type E spores and Bacillus spores although both organisms have significantly different HPT resistance properties. The information presented here contributes to closing the gap in knowledge regarding the HPT inactivation of spore formers relevant to food safety and may help industrial implementation of HPT processing. The markedly lower HPT resistance of C. botulinum type E spores compared with the resistance of spores from other C. botulinum types could allow for the implementation of milder processes without endangering food safety.
Project description:There is a growing interest in developing dynamically responsive hydrogels whose material properties are modulated by environmental cues, including with light. These photoresponsive hydrogels afford spatiotemporal control of material properties through an array of photoaddition and photodegradation reactions. For photoresponsive hydrogels to be utilized most effectively in a broad range of applications, the photoreaction behavior should be well understood, enabling the design of dynamic materials with uniform or anisostropic material properties. Here, a general statistical-kinetic model has been developed to describe controlled photodegradation in hydrogel polymer networks containing photolabile crosslinks. The heterogeneous reaction rates that necessarily accompany photochemical reactions were described by solving a system of partial differential equations that quantify the photoreaction kinetics in the material. The kinetics were coupled with statistical descriptions of network structure in chain polymerized hydrogels to model material property changes and mass loss that occur during the photodegradation process. Finally, the physical relevance of the model was demonstrated by comparing model predictions with experimental data of mass loss and material property changes in photodegradable, PEG-based hydrogels.
Project description:Introduction: Beta-Boswellic acid (BBA) is a pentacyclic terpene which has been obtained from frankincense and its beneficial effects on neurodegenerative disorders such as Alzheimer's disease (AD) have been addressed. Methods: In the present study, thermodynamic and kinetic aspects of BBA interaction with Tau protein as one of the important proteins involved in AD in the absence and presence of glucose has been investigated using surface plasmon resonance (SPR) method. Tau protein was immobilized onto the carboxy methyl dextran chip and its binding interactions with BBA were studied at physiological pH at various temperatures. Glucose interference with these interactions was also investigated. Results: Results showed that BBA forms a stable complex with Tau (KD=8.45×10-7 M) at 298 K. Molecular modeling analysis showed a hydrophobic interaction between BBA and HVPGGG segment of R2 and R4 repeated domains of Tau. Conclusion: The binding affinity increased by temperature enhancement, while it decreased significantly in the presence of glucose. Both association and dissociation of the BBA-Tau complex were accompanied with an entropic activation barrier; however, positive enthalpy and entropy changes revealed that hydrophobic bonding is the main force involved in the interaction.
Project description:Molecular density information (as measured by electron microscopic reconstructions or crystallographic density maps) can be a powerful source of information for molecular modeling. Molecular density constrains models by specifying where atoms should and should not be. Low-resolution density information can often be obtained relatively quickly, and there is a need for methods that use it effectively. We have previously described a method for scoring molecular models with surface envelopes to discriminate between plausible and implausible fits. We showed that we could successfully filter out models with the wrong shape based on this discrimination power. Ideally, however, surface information should be used during the modeling process to constrain the conformations that are sampled. In this paper, we describe an extension of our method for using shape information during computational modeling. We use the envelope scoring metric as part of an objective function in a global optimization that also optimizes distances and angles while avoiding collisions. We systematically tested surface representations of proteins (using all nonhydrogen heavy atoms) with different abundance of distance information and showed that the root mean square deviation (RMSD) of models built with envelope information is consistently improved, particularly in data sets with relatively small sets of short-range distances.
Project description:Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances.