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A molecular switch based on the metastable radical anion derived from a substituted heteroaryl quinone is described. Pyrrolyl quinone thiocyanate (PQ 9) showed an interaction with the fluoride anion that was visible to the naked eye and quantified by UV/vis and 1H and 13 C NMR. The metastable quinoid species formed by the interaction with F- ("ON" state) showed a molecular switching effect autocontrolled by the presence of ascorbate ("OFF" state) and back to the "ON" state by an autooxidation process, measured by visible and UV/vis spectroscopy. Due to its out-of-equilibrium properties and the exchange of matter and energy, a dissipative structural behaviour is proposed. Considering its similarity to the mechanism of coenzyme Q in oxidative phosphophorylation, PQ 9 was evaluated on Saccharomyces cerevisiae mitochondrial function for inhibition of complexes II, III and IV, reactive oxygen species (ROS) production, catalase activity and lipid peroxidation. The results showed that PQ 9 inhibited complex III activity as well as the activity of all electron transport chain (ETC) complexes. In addition, PQ 9 reduced ROS production and catalase activity in yeast. The results suggest that PQ 9 may have potential applications as a new microbicidal compound by inducing ETC dysfunction.

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Recent progress in out-of-equilibrium closed quantum systems has significantly advanced the understanding of mechanisms behind their evolution toward thermalization. Notably, the concept of nonthermal fixed points (NTFPs)-responsible for the emergence of spatiotemporal universal scaling in far-from-equilibrium systems-has played a crucial role in both theoretical and experimental investigations. In this work, we introduce a differential equation that has the universal scaling associated with NTFPs as a solution. The advantage of working with a differential equation, rather than only with its solution, is that we can extract several insightful properties not necessarily present in the solution alone. How the differential equation is derived allows physical interpretation of the universal exponents in terms of the time dependence of the amplitude of the distributions and their momentum scaling. Employing two limiting cases of the equation, we determined the universal exponents related to the scaling using the distributions near just two momentum values. We established a solid agreement with previous investigations by validating this approach with three distinct physical systems. This consistency highlights the universal nature of scaling due to NTFPs and emphasizes the predictive capabilities of the proposed differential equation. Moreover, under specific conditions, the equation predicts a power-law related to the ratio of the two universal exponents, leading to implications concerning particle and energy transport. This suggests that the observed power-laws in far-from-equilibrium turbulent fluids could be related to the universal scaling due to NTFPs, potentially offering insights into the study of turbulence.

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The Biswas-Chatterjee-Sen (BChS) model of opinion dynamics has been studied on three-dimensional Solomon networks by means of extensive Monte Carlo simulations. Finite-size scaling relations for different lattice sizes have been used in order to obtain the relevant quantities of the system in the thermodynamic limit. From the simulation data it is clear that the BChS model undergoes a second-order phase transition. At the transition point, the critical exponents describing the behavior of the order parameter, the corresponding order parameter susceptibility, and the correlation length, have been evaluated. From the values obtained for these critical exponents one can confidently conclude that the BChS model in three dimensions is in a different universality class to the respective model defined on one- and two-dimensional Solomon networks, as well as in a different universality class as the usual Ising model on the same networks.

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This study investigates the equilibrium state diagram of maltodextrins with varying dextrose equivalents (DE 10 and 30) for quercetin microencapsulation. Using XRD, SEM, and optical microscopy, three transition regions were identified: amorphous (aw 0.07-0.437), semicrystalline (aw 0.437-0.739), and crystalline (aw > 0.739). In the amorphous region, microparticles exhibit a spherical morphology and a fluffy, pale-yellow appearance, with Tg values ranging from 44 to -7 °C. The semicrystalline region shows low-intensity diffraction peaks, merged spherical particles, and agglomerated, intense yellow appearance, with Tg values below 2 °C. The crystalline region is characterized by fully collapsed microstructures and a continuous, solid material with intense yellow color. Optimal storage conditions are within the amorphous region at 25 °C, aw 0.437, and a water content of 1.98 g H2O per g of dry powder. Strict moisture control is required at higher storage temperatures (up to 50 °C) to prevent microstructural changes. This research enhances understanding of maltodextrin behavior across diverse dextrose equivalents, aiding the development of stable microencapsulated products.

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This study aimed to investigate the liquid-liquid equilibrium (LLE) behavior of sesame fatty acid ethyl ester (FAEE) and methyl ester (FAME) in combination with glycerol and the co-solvents ethanol and methanol. FAEE and FAME were produced through the transesterification of mechanically extracted and purified sesame oil, using potassium hydroxide (KOH) as a homogeneous base catalyst. The reactions were conducted in ethanol and methanol to produce FAEE and FAME, respectively. Post-reaction, the products were separated and purified, followed by an analysis of the LLE behavior at 313.15 K and 323.15 K under atmospheric pressure (101.3 kPa). The experimental process for the miscibility analysis utilized a jacketed glass cell adapted for this study. Miscibility limits or binodal curves were determined using the turbidity-point method. Tie lines were constructed by preparing mixtures of known concentrations within the two-phase region, which allowed the phases to separate after agitation. Samples from both phases were analyzed to determine their composition. This study revealed that higher temperatures promoted greater phase separation and enhanced the biodiesel purification process. The NRTL model effectively correlated the activity coefficients with the experimental data, showing good agreement, with a root-mean-square deviation of 3.5%. Additionally, the data quality was validated using Marcilla's method, which yielded an R2 value close to 1. Attraction factors and distribution coefficients were also calculated to evaluate the efficiency of the co-solvents as extraction agents. The findings indicated higher selectivity for methanol than for ethanol, with varying degrees of distribution among the co-solvents. These results offer significant insights into enhancing biodiesel production processes by considering the effects of co-solvents on the LLE properties of mixtures, ultimately contributing to more efficient and cost-effective biodiesel production.

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Jatobá-do-cerrado fruit shells, archetypical of lignocellulosic-based biomass, were used as an adsorbent to remove crystal violet (CV) and methylene blue (MB) from water. The adsorbent was characterized using various techniques, and kinetic studies showed dye adsorption followed second-order kinetics. An experimental design investigated the effects of pH and temperature on removal efficiency, with a quadratic model fitting the data best. The results suggest pH influences MB's adsorption capacity more than temperature and at 25 °C and pH 8, MB had a desirability value of 0.89, with 95 % removal efficiency. For CV, temperature had a greater influence, with a desirability value of 0.874 at 25 °C and pH 10, and 95 % removal efficiency. Adsorption isotherm studies revealed maximum adsorption capacities of 123.0 mg·g-1 and 113.0 mg·g-1 for CV and MB, respectively. Experimental thermodynamic parameters indicated an endothermic and spontaneous process which it was supported by quantum chemistry calculations. The protocols developed confirmed the potential for adsorbing CV and MB dyes in water, achieving over 73.1 and 74.4 mg g-1 dyes removal.

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COVID-19 has a broad clinical spectrum, ranging from asymptomatic-mild form to severe phenotype. The severity of COVID-19 is a complex trait influenced by various genetic and environmental factors. Ethnic differences have been observed in relation to COVID-19 severity during the pandemic. It is currently unknown whether genetic variations may contribute to the increased risk of severity observed in Latin-American individuals The aim of this study is to investigate the potential correlation between gene variants at CCL2, OAS1, and DPP9 genes and the severity of COVID-19 in a population from Quito, Ecuador. This observational case-control study was conducted at the Carrera de Biologia from the Universidad Central del Ecuador and the Hospital Quito Sur of the Instituto Ecuatoriano de Seguridad Social (Quito-SUR-IESS), Quito, Ecuador. Genotyping for gene variants at rs1024611 (A>G), rs10774671 (A>G), and rs10406145 (G>C) of CCL2, OAS1, and DPP9 genes was performed on 100 COVID-19 patients (43 with severe form and 57 asymptomatic-mild) using RFLP-PCR. The genotype distribution of all SNVs throughout the entire sample of 100 individuals showed Hardy Weinberg equilibrium (P=0.53, 0.35, and 0.4 for CCL2, OAS1, and DPP9, respectively). The HWE test did not find any statistically significant difference in genotype distribution between the study and control groups for any of the three SNVs. The multivariable logistic regression analysis showed that individuals with the GG of the CCL2 rs1024611 gene variant had an increased association with the severe COVID-19 phenotype in a recessive model (P = 0.0003, OR = 6.43, 95% CI 2.19-18.89) and for the OAS1 rs10774671 gene variant, the log-additive model showed a significant association with the severe phenotype of COVID-19 (P=0.0084, OR=3.85, 95% CI 1.33-11.12). Analysis of haplotype frequencies revealed that the coexistence of GAG at CCL2, OAS1, and DPP9 variants, respectively, in the same individual increased the presence of the severe COVID-19 phenotype (OR=2.273, 95% CI: 1.271-4.068, P=0.005305). The findings of the current study suggests that the ethnic background affects the allele and genotype frequencies of genes associated with the severity of COVID-19. The experience with COVID-19 has provided an opportunity to identify an ethnicity-based approach to recognize genetically high-risk individuals in different populations for emerging diseases.

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Upgrading biogas to biomethane is of great interest to change the energy matrix by feeding the renewable fuel produced from biomass waste into natural gas grids or directly using it to replace fossil fuels. The study aimed to assess the adsorption equilibrium of CH4, CO2, and H2O on a coconut-shell activated carbon (CAC 8X30) to provide data for further studies on its efficiency in upgrading biogas by Pressure Swing Adsorption (PSA). The adsorbent was characterized, and equilibrium parameters were estimated from monocomponent CH4, CO2, and H2O equilibrium isotherms. Binary and ternary equilibrium isotherms were simulated, and the selectivity and adsorption capacity of the CAC 8X30 were calculated in dry and wet conditions and then compared with zeolite 13X as a reference material. Regarding characterization, Nitrogen and Hydrogen Physisorption results indicated that 94 % of the pore volume is concentrated in the region of micropores. The adsorption affinity with CAC 8X30 estimated from monocomponent isotherms was in the order KH20>KCO2>KCH4. IAST-Langmuir model simulations presented good agreement with experimental binary equilibrium data. Further simulations indicated equilibrium selectivity for CO2 over CH4 (e.g., 4.7 at 1 bar and 298 K for a mixture of CH4/CO2, 60/40 vol%), which increased in the presence of moisture, indicating its suitability for upgrading humid biogas. Simulations for zeolite 13X suggested that the material is unsuitable in the presence of water vapor but presents higher selectivity than the CAC 8X30 in dry conditions. Hence, the integration of both materials might be helpful for biogas upgrading.

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PURPOSE: Most T1 and T2 mapping take long acquisitions or needs specialized sequences not widely accessible on clinical scanners. An available solution is DESPOT1/T2 (Driven equilibrium single pulse observation of T1/T2). DESPOT1/T2 uses Spoiled gradient-echo (SPGR) and balanced Steady-State Free Precession (bSSFP) sequences, offering an accessible and reliable way for 3D accelerated T1/T2 mapping. However, bSSFP is prone to off-resonance artifacts, limiting the application of DESPOT2 in regions with high susceptibility contrasts, like the prostate. Our proposal, DESPO+, employs the full bSSFP and SPGR models with a dictionary-based method to reconstruct 3D T1/T2 maps in the prostate region without off-resonance banding. METHODS: DESPO+ modifies the bSSFP acquisition of the original variable flip angle DESPOT2. DESPO+ uses variable repetition and echo times, employing a dictionary-based method of the full bSSFP and SPGR models to reconstruct T1, T2, and Proton Density (PD) simultaneously. The proposed DESPO+ method underwent testing through simulations, T1/T2 phantoms, and on fourteen healthy subjects. RESULTS: The results reveal a significant reduction in T2 map banding artifacts compared to the original DESPOT2 method. DESPO+ approach reduced T2 errors by up to seven times compared to DESPOT2 in simulations and phantom experiments. We also synthesized in-vivo T1-weighted/T2-weighted images from the acquired maps using a spin-echo model to verify the map's quality when lacking a reference. For in-vivo imaging, the synthesized images closely resemble those from the clinical MRI protocol, reducing scan time by around 50% compared to traditional spin-echo T1-weighted/T2-weighted acquisitions. CONCLUSION: DESPO+ provides an off-resonance insensitive and clinically available solution, enabling high-resolution 3D T1/T2 mapping and synthesized T1-weighted/T2-weighted images for the entire prostate, all achieved within a short scan time of 3.6 min, similar to DESPOT1/T2.

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The chemokine Cxcl1 plays a crucial role in recruiting neutrophils in response to infection. The early events in chemokine-mediated neutrophil extravasation involve a sequence of highly orchestrated steps including rolling, adhesion, arrest, and diapedesis. Cxcl1 function is determined by its properties of reversible monomer-dimer equilibrium and binding to Cxcr2 and glycosaminoglycans. Here, we characterized how these properties orchestrate extravasation using intravital microscopy of the cremaster. Compared to WT Cxcl1, which exists as both a monomer and a dimer, the trapped dimer caused faster rolling, less adhesion, and less extravasation. Whole-mount immunofluorescence of the cremaster and arrest assays confirmed these data. Moreover, the Cxcl1 dimer showed impaired LFA-1-mediated neutrophil arrest that could be attributed to impaired Cxcr2-mediated ERK signaling. We conclude that Cxcl1 monomer-dimer equilibrium and potent Cxcr2 activity of the monomer together coordinate the early events in neutrophil recruitment.

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The removal of dyes from effluents of textile industries represents a technological challenge, due to their significant environmental impact. The application of halloysite (Hal) and palygorskite (Pal) clay minerals as adsorbents for the removal of Congo red (CR) and methylene blue (MB) was evaluated in this work. The materials were applied both in natural and acid-treated forms, and characterized by XRD, XPS, SEM-EDS, FTIR, and N2 adsorption-desorption isotherm techniques to identify their properties and main active sites. The adsorbents showed potential to remove CR (> 98%) and MB (> 85%) within 180 min, using 0.3 g adsorbent and initial dye concentration of 250 mg L-1. Semi-empirical quantum mechanical calculations (SQM) confirmed the interaction mechanism between dyes and the adsorbents via chemisorption (- 69.0 kcal mol-1 < Eads < - 28.8 kcal mol-1), which was further observed experimentally due to the high fit of adsorption data to pseudo-second order kinetic model (R2 > 0.99) and Langmuir isotherm (R2 > 0.98). The use of Pal and Hal to remove dyes was proven to be economically and environmentally viable for industrial application.

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Simulation and rigorous design of industrial dryers combine a large number of models, which feed three fundamental balances: (1) mass; (2) energy; and (3) quantity of movement of the material through the dryer. Many of these models represent physical phenomena affecting the three balances at the same time, which makes these calculations extremely complex, hence, accurate models are essential. The hypothesis that the kinetic stage of drying of any material culminates in the thermodynamic moisture equilibrium between solid and drying gas has been in effect for many years. However, recent findings show that there is a transition stage between the kinetic stage and the thermodynamic equilibrium, which, experimentally, looks like an equilibrium. The beginning of this transition stage or dynamic pseudo-equilibrium stage would mark the end of the drying kinetics models, which has been named as the dynamic pseudo-equilibrium moisture contents (Xdpe). The non-observance of this phenomenon presupposes a model limited in its prediction capacity, especially in the last stages of drying and even more so at low drying temperatures. As a consequence, sizes of industrial dryers could be underestimated during the simulation and rigorous design process, or underestimate drying times, in batch dryers. On the other hand, the optimal conditions may never be found, during the optimization of existing industrial drying processes. The objective of this work is to present the procedure to determine Xdpe, during the experimental determination of drying curves of any material. Likewise, to propose the practical moisture ratio, which uses Xdpe, instead of the equilibrium moisture, to be used in the modeling of the drying kinetics.•The drying process is divided into three stages: kinetic, transition, and equilibrium.•The dynamic pseudo-equilibrium moisture content divides the kinetic and the transition stages.•The practical moisture ratio should be used in rigorous industrial dryer design calculations.

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In this article, we address the reliance on probability density functions to obtain macroscopic properties in systems with multiple degrees of freedom as plasmas, and the limitations of expensive techniques for solving Equations such as Vlasov's. We introduce the Ehrenfest procedure as an alternative tool that promises to address these challenges more efficiently. Based on the conjugate variable theorem and the well-known fluctuation-dissipation theorem, this procedure offers a less expensive way of deriving time evolution Equations for macroscopic properties in systems far from equilibrium. We investigate the application of the Ehrenfest procedure for the study of adiabatic invariants in magnetized plasmas. We consider charged particles trapped in a dipole magnetic field and apply the procedure to the study of adiabatic invariants in magnetized plasmas and derive Equations for the magnetic moment, longitudinal invariant, and magnetic flux. We validate our theoretical predictions using a test particle simulation, showing good agreement between theory and numerical results for these observables. Although we observed small differences due to time scales and simulation limitations, our research supports the utility of the Ehrenfest procedure for understanding and modeling the behavior of particles in magnetized plasmas. We conclude that this procedure provides a powerful tool for the study of dynamical systems and statistical mechanics out of equilibrium, and opens perspectives for applications in other systems with probabilistic continuity.

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Coffee is a relevant agricultural product in the global economy, with the amount and quality of the bean being seriously affected by the coffee berry borer Hypothenemus hampei (Ferrari), CBB, its principal pest. One of the ways to deal with this beetle is through biological control agents, like ants (Hymenoptera: Formicidae), some of which are characterized by naturally inhabiting coffee plantations and feeding on CBB in all their life stages. Our paper considers a predator-prey interaction between these two insects through a novel mathematical model based on ordinary differential equations, where the state variables correspond to adult CBBs, immature CBBs, and ants from one species, without specifying whether preying on the CBB is among their feeding habits, in both adult and immature stages. Through this new mathematical model, we could qualitatively predict the different dynamics present in the system as some meaningful parameters were varied, filling the existing gap in the literature and envisioning ways to manage pests. Mathematically, the system's equilibrium points were determined, and its stability was studied through qualitative theory. Bifurcation theory and numerical simulations were applied to illustrate the stability of the results, which were interpreted as conditions of the coexistence of the species, as well as conditions for eradicating the pest, at least theoretically, through biocontrol action in combination with other actions focused on eliminating only adult CBBs.

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A grafting of N1-(3-trimethoxysilylpropyl)diethylenetriamine (TMSPDETA) on natural clay was carried out to obtain an organic-inorganic hybrid clay material that was applied as an adsorbent to the uptake of Reactive Blue 19 (RB-19) and Reactive Green 19 (RG-19) dyes from aqueous wastewaters. This research demonstrates the effect of TMSPDETA contents on amino-functionalized clay materials' hydrophobic/hydrophilic behavior. The resultant material was utilized to uptake reactive dyes in aqueous solutions. The clay@TMSPDETA hybrid material was characterized by isotherm of adsorption and desorption of nitrogen, FTIR, elemental analysis, TGA, pHpzc, total acidity, total basicity groups, and hydrophilic balance. The hybrid samples were more hydrophilic than the pristine clay for ratios from 0.1 up to 0.5 due to adding amino groups to the pristine clay. FTIR spectra suggest that TMSPDETA was grafted onto the clay. The hybrid material presents a surface area 2.17-fold (42.7 m2/g) lower than pristine clay (92.7 m2/g). The total volume of pores of hybrid material was 0.0822 cm3/g, and the pristine clay material was 0.127 cm3/g, corresponding to a diminution of the total pore volume (Vtot) of 1.54 times. The kinetic data followed the pseudo-second-order (PSO) model for RB-19 and RG-19 reactive dyes. The equilibrium data were better fitted to the Liu isotherm model, displaying a Qmax as 178.8 and 361.1 mg g-1 for RB-19 and RG-19, respectively, at 20.0 °C. The main mechanism of interactions of the reactive dyes with the hybrid clay is electrostatic interaction. The clay@TMSPDETA has a very good effect on treating synthetic dye-textile wastewater. The removal percentage of simulated wastewater was up to 97.67% and 88.34% using distilled water and plastic industry wastewater as the solvents, respectively. The clay@TMSPDETA-0.1 could be recycled up to 5 cycles of adsorption and desorption of both dyes, attaining recoveries of 98.42% (RB-19) and 98.32% (RG-19) using 0.1 M HCl + 10% ethanol.

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Entropy density behavior poses many problems when we study non-equilibrium situations. In particular, the local equilibrium hypothesis (LEH) has played a very important role and is taken for granted in non-equilibrium problems, no matter how extreme they are. In this paper we would like to calculate the Boltzmann entropy balance equation for a plane shock wave and show its performance for Grad's 13-moment approximation and the Navier-Stokes-Fourier equations. In fact, we calculate the correction for the LEH in Grad's case and discuss its properties.

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We present a thorough numerical analysis of the relaxational dynamics of the Sherrington-Kirkpatrick spherical model with an additive non-disordered perturbation for large but finite sizes N. In the thermodynamic limit and at low temperatures, the perturbation is responsible for a phase transition from a spin glass to a ferromagnetic phase. We show that finite-size effects induce the appearance of a distinctive slow regime in the relaxation dynamics, the extension of which depends on the size of the system and also on the strength of the non-disordered perturbation. The long time dynamics are characterized by the two largest eigenvalues of a spike random matrix which defines the model, and particularly by the statistics concerning the gap between them. We characterize the finite-size statistics of the two largest eigenvalues of the spike random matrices in the different regimes, sub-critical, critical, and super-critical, confirming some known results and anticipating others, even in the less studied critical regime. We also numerically characterize the finite-size statistics of the gap, which we hope may encourage analytical work which is lacking. Finally, we compute the finite-size scaling of the long time relaxation of the energy, showing the existence of power laws with exponents that depend on the strength of the non-disordered perturbation in a way that is governed by the finite-size statistics of the gap.

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This research analyses the Prospera program's impact on poverty and income distribution through a computable general equilibrium model. It concludes that transfers to households have a positive impact on the Mexican economy but hide the real problem-the low wage share-that, in the long term, prevents poverty from worsening but does not reduce the population in poverty or inequality. In a scenario without transfers, neither the population in poverty nor the Gini Index decreases significantly. The results obtained lead to an understanding of some of the causes of the high rates of poverty and inequality in Mexico, which in turn have been perpetuated since the economic crisis of 1995. This allows the design of public policies in line with the structural needs of the economy, which combat the problem from the root that generates it, in order to contribute to the reduction of inequality in accordance with the UN Sustainable Development Goal 10.

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Covid-19, caused by severe acute respiratory syndrome coronavirus 2, broke out as a pandemic during the beginning of 2020. The rapid spread of the disease prompted an unprecedented global response involving academic institutions, regulatory agencies, and industries. Vaccination and nonpharmaceutical interventions including social distancing have proven to be the most effective strategies to combat the pandemic. In this context, it is crucial to understand the dynamic behavior of the Covid-19 spread together with possible vaccination strategies. In this study, a susceptible-infected-removed-sick model with vaccination (SIRSi-vaccine) was proposed, accounting for the unreported yet infectious. The model considered the possibility of temporary immunity following infection or vaccination. Both situations contribute toward the spread of diseases. The transcritical bifurcation diagram of alternating and mutually exclusive stabilities for both disease-free and endemic equilibria were determined in the parameter space of vaccination rate and isolation index. The existing equilibrium conditions for both points were determined in terms of the epidemiological parameters of the model. The bifurcation diagram allowed us to estimate the maximum number of confirmed cases expected for each set of parameters. The model was fitted with data from São Paulo, the state capital of SP, Brazil, which describes the number of confirmed infected cases and the isolation index for the considered data window. Furthermore, simulation results demonstrate the possibility of periodic undamped oscillatory behavior of the susceptible population and the number of confirmed cases forced by the periodic small-amplitude oscillations in the isolation index. The main contributions of the proposed model are as follows: A minimum effort was required when vaccination was combined with social isolation, while additionally ensuring the existence of equilibrium points. The model could provide valuable information for policymakers, helping define disease prevention mitigation strategies that combine vaccination and non-pharmaceutical interventions, such as social distancing and the use of masks. In addition, the SIRSi-vaccine model facilitated the qualitative assessment of information regarding the unreported infected yet infectious cases, while considering temporary immunity, vaccination, and social isolation index.

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Resumen La uroporfirinógeno descarboxilasa humana (UROD-h) es la quinta enzima del camino biosintético del hemo y su actividad deficiente, relacionada a mutaciones en su gen, se encuentra asociada a un subgrupo de porfirias. El objetivo de este trabajo fue estudiar la relación entre la dimerización de la enzima y su actividad enzimática y comprobar si la dimerización de UROD-h es imprescindible tanto para la primera etapa de la reacción (urogen→heptagen), como para la segunda etapa (heptagen→coprogen). Con ese objetivo, se expresó y purificó la UROD-h hasta homogeneidad, se analizó el comportamiento dímero-monómero bajo distintas condiciones que pudieran desplazar el equilibrio de dimerización y se evaluó la actividad enzimática en dichas condiciones. Los resultados obtenidos sugieren que la especie activa para la primera etapa de la reacción es el homodímero y que tanto el dímero como el monómero se comportan como especies activas para la segunda etapa de la reacción. Se propone que mutaciones clínicas como la Y311C, existentes en pacientes con porfiria cutánea tarda, podrían afectar la estabilidad del dímero y podrían ser el blanco para futuras terapias génicas.

Abstract Human uroporphyrinogen decarboxylase (UROD-h) is the fifth enzyme in the heme biosynthetic pathway and its deficient activity, related to mutations in its gene, is associated with a subset of porphyrias. The objective of this work was to study the relationship between the dimerisation of the enzyme and its enzymatic activity and to verify if the dimerisation of UROD-h is essential both for the first stage of the reaction (urogen→heptagen), and for the second stage (heptagen→ coprogen). With this objective, the UROD-h was expressed and purified to homogeneity, the dimer- monomer behaviour was analysed under different conditions, which could shift the dimerisation equilibrium, and the enzymatic activity was evaluated under these conditions. The results obtained suggest that the active species for the first stage of the reaction is the homodimer, and both the dimer and the monomer behaved as active species for the second stage of the reaction. It is proposed that clinical mutations such as Y311C, existing in porphyria cutanea tarda patients, could affect dimer stability and could be the target of future gene therapies.

Resumo A enzima uroporfirinogênio descarboxilase humana (UROD-h) é a quinta enzima da via biossintética do heme e sua atividade deficiente, relacionada com mutações em seu gene, está associada a um subgrupo de porfirias. O objetivo deste trabalho foi estudar a relação entre a dimerização da enzima e sua atividade enzimática e comprovar se a dimerização da UROD-h é imprescindível tanto para a primeira etapa da reação (urogênio→heptagênio), quanto para a segunda etapa (heptagênio→coprogênio). Com esse objetivo, a UROD-h foi expressa e purificada até a homogeneidade, o comportamento de dímero-monômero foi analisado sob diversas condições, que puderam deslocar o equilíbrio de dimerização, e a atividade enzimática foi avaliada em tais condições. Os resultados obtidos sugerem que a espécie ativa para a primeira etapa da reação é o homodímero, e tanto o dímero quanto o monômero se comportam como espécies ativas para a segunda etapa da reação. Propõe-se que mutações clínicas como Y311C, existentes em pacientes com porfiria cutânea tardia, poderiam afetar a estabilidade do dímero e poderiam ser o alvo de futuras terapias gênicas em porfiria cutânea tardia.