Aspects Of Reactions Research Articles

Modeling the Hydrolysis of Iron-Sulfur Clusters.

Iron-sulfur (FeS) clusters are essential metal cofactors involved in a wide variety of biological functions. Their catalytic efficiency, biosynthesis, and regulation depend on FeS stability in aqueous solution. Here, molecular modeling is used to investigate the hydrolysis of an oxidized (ferric) mononuclear FeS cluster by bare dissociation and water substitution mechanisms in neutral and acidic solution. First, approximate electronic structure descriptions of FeS reactions by density functional theory are validated against high-level wave function CCSD(T) calculations. Solvation contributions are included by an all-atom model with hybrid quantum chemical/molecular mechanical (QM/MM) potentials and enhanced sampling molecular dynamics simulations. The free energy profile obtained for FeS cluster hydrolysis indicates that the hybrid functional M06 together with an implicit solvent correction capture the most important aspects of FeS cluster reactivity in aqueous solution. Then, 20 reaction channels leading to two consecutive Fe-S bond ruptures were explored with this calibrated model. For all protonation states, nucleophilic substitution with concerted bond breaking and forming to iron is the preferred mechanism, both kinetic and thermodynamically. In neutral solution, proton transfer from water to the sulfur leaving group is also concerted. Dissociative reactions show higher barriers and will not be relevant for FeS reactivity when exposed to solvent. These hydrolysis mechanisms may help to explain the stability and catalytic mechanisms of FeS clusters of multiple sizes and proteins.

(Hydr)oxo-bridged heme complexes: From structure to reactivity

Iron–porphyrins ([Formula: see text] hemes) are present throughout the biosphere and perform a wide range of functions, particularly those that involve complex multiple-electron redox processes. Some common heme enzymes involved in these processes include cytochrome P450, heme/copper oxidase or heme/non-heme diiron nitric oxide reductase. Consequently, the (hydr)oxo-bridged heme species have been studied for the important roles that they play in many life processes or for their application for catalysis and preparation of new functional materials. This review encompasses important synthetic, structural and reactivity aspects of the (hydr)oxo-bridged heme constructs that govern their function and application. The properties and reactivity of the bridging (hydr)oxo moieties are directly dictated by the coordination environment of the heme core, the nature and ligation of the second metal center attached to the (hydr)oxo group, the presence or absence of a linker, and the degree of flexibility around that linker within the scaffold. Here, we summarize the structural features of all known (hydr)oxo-bridged heme constructs and use those to categorize and thus, provide a more comprehensive picture of structure–function relationships.

The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli.

Finasteride (FIN) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. FIN is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, FIN has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of FIN, however, remains controversial, in view of inconsistent clinical reports. Here, we tested the effects of FIN in a battery of tests aimed at capturing complementary aspects of mood regulation and stress reactivity in rats. FIN reduced exploratory, incentive, prosocial, and risk-taking behavior; furthermore, it decreased stress coping, as revealed by increased immobility in the forced-swim test (FST). This last effect was also observed in female and orchiectomized male rats, suggesting that the mechanism of action of FIN does not primarily reflect changes in gonadal steroids. The effects of FIN on FST responses were associated with a dramatic decrease in corticotropin release hormone (CRH) mRNA and adrenocorticotropic hormone (ACTH) levels. These results suggest that FIN impairs stress reactivity and reduces behavioral activation and impulsive behavior by altering the function of the hypothalamus–pituitary–adrenal (HPA) axis.

Synergistic Effects of Interferon-γ and Vitamin D3 Signaling in Induction of ILT-3highPDL-1high Tolerogenic Dendritic Cells.

In the past, interferon (IFN)-γ and vitamin D3 (vit D3) have both been associated with induction of tolerogenic characteristics in human dendritic cells (DCs). Although there are only a few reports on interdependency of their actions, the interplay between IFN-γ and vit D3 has been clearly demonstrated in certain aspects of immune reactivity. Since both agents have been associated with regulation of immune responses, we set out to examine their functional and mechanistic interactions in context of principal regulators of immunity, the DCs. Combined treatment with vit D3 and IFN-γ caused an extensive expression of immunoglobulin-like transcript (ILT)-3 and programmed death ligand (PDL)-1 on γ/D3DCs, significantly greater than that caused by vit D3 alone. Such γ/D3DCs retained all general DC characteristics. After CD40 ligand-induced activation, they produced increased amounts of IL-10 with almost absent production of IL-12p70. On the other hand, the co-stimulatory potential of γ/D3DCs was weak, with cells possessing the capacity to inhibit CD4+ T cell, CD8+ T cell, as well as memory T cell responses. Naive CD4+ T cells stimulated with γ/D3DCs produced increased amounts of IL-10 with concomitantly low IFN-γ production, upon T cell receptor activation. Additionally, γ/D3DCs completely inhibited granzyme B expression by CD8+ T cells. The percentage of FoxP3-positive cells in co-cultures with naive CD4+ T cells was significantly higher where γ/D3DCs were used as stimulators compared to DCs treated with vit D3 alone and it could be partially reversed by PDL-1 blockade. Interestingly, γ/D3DCs were inefficient at suppressing mDC-induced CD4+ T cell proliferation, but were twice as effective as D3DCs at suppressing mDC-induced CD8+ T cell proliferation. Blockade of indoleamine-2,3-dioxygenase did not reduce the tolerogenic phenotype induced by IFN-γ and vit D3 treatment. Examination of signaling pathways activation revealed a tendency toward increased ERK and Akt phosphorylation in γ/D3DCs. Inhibition of MEK/ERK and PI3K/mTOR pathways significantly reduced the expression of ILT-3 and PDL-1 on γ/D3DCs. In summary, we present the first evidence for existing synergy between IFN-γ and vit D3 in shaping a unique tolerogenic DC activation state.

Organodiselenides: Organic Catalysis and Drug Design Learning from Glutathione Peroxidase

Organodiselenides are an important class of compounds characterized by the presence of two adjacent covalently bonded selenium nuclei. Among them, diaryldiselenides and their parent compound diphenyl diselenide attract continuing interest in chemistry as well as in close disciplines like medicinal chemistry, pharmacology and biochemistry. A search in SCOPUS database has revealed that in the last three years 105 papers have been published on the archetypal diphenyl diselenide and its use in organic catalysis and drug tests. The reactivity of the Se-Se bond and the redox properties of selenium make diselenides efficient catalysts for numerous organic reactions, such as Bayer- Villiger oxidations of aldehydes/ketones, epoxidations of alkenes, oxidations of alcohols and nitrogen containing compounds. In addition, organodiselenides might find application as mimics of glutathione peroxidase (GPx), a family of enzymes, which, besides performing other functions, regulate the peroxide tone in the cells and control the oxidative stress level. In this review, the essential synthetic and reactivity aspects of organoselenides are collected and rationalized using the results of accurate computational studies, which have been carried out mainly in the last two decades. The results obtained in silico provide a clear explanation of the anti-oxidant activity of organodiselenides and more in general of their ability to reduce hydroperoxides. At the same time, they are useful to gain insight into some aspects of the enzymatic activity of the GPx, inspiring novel elements for rational catalyst and drug design.

Revisiting the mechanism for the polar hydrochlorination of alkenes.

Various kinetic studies of the addition of hydrogen halides to alkenes were carried out in the 1930s, 1940s, and 1970s. Since then, there have been theoretical analyses of several aspects of alkene reactivity and regioselectivity during hydrohalogenation. A few works have studied the influence of the hydrogen halide when it is acting as a catalyst (as well as a reactant) under third-order kinetics. However, there has not been any theoretical investigation of the possibility that there is a carbocation intermediate in the contact ion pair. Therefore, we revisited the mechanistic aspects of this reaction at different levels of theory and using IRC (in a gaseous medium) and ONIOM (with an explicit solvent model). We found that (i) there is only one transition state (one energy barrier) for all possible reaction mechanisms in an apolar medium, (ii) there is no carbocation intermediate when a hydrohalogenation reaction is performed in apolar and polar protic media, (iii) hydrochlorination in apolar and polar protic media occurs through an asynchronous concerted mechanism (not through the stepwise mechanism described in undergraduate/graduate literature), and (iv) there are three possible competing mechanisms (with second-, third-, and fourth-order kinetics) in an apolar medium; the mechanism with fourth-order kinetics has the smallest energy barrier, while that with second-order kinetics (a mechanism in which the hydrogen halide does not also act as a catalyst) has the highest energy barrier. Graphical abstract Hydrochlorination of 2,3-dimethylbutene through an asynchronous concerted mechanism.

Theoretical investigation of peristalsis transport in flow of hyperbolic tangent fluid with slip effects and chemical reaction

This study addresses the peristalsis of tangent hyperbolic liquid in a curved channel. Analysis has been prepared for chemical reaction, magnetohydrodynamics and thermophoretic deposition. The slip conditions for velocity, temperature and concentration are imposed. Problem subject to low Reynolds number and long wavelength are constructed. Numerical approach (called shooting method with the combination of Runge-Kutta Fehlberg algorithm) is employed to find the solutions. Behavior of velocity, temperature and concentration for sundry parameters is plotted. Graphical results reveal that velocity and temperature have opposite behavior for their respective slip parameters (i.e. velocity and thermal). Aspects of chemical reaction (for both constructive and destructive cases) on concentration are quite prominent.

Cerebrovascular Resistance in Healthy Aging and Mild Cognitive Impairment.

Measures of cerebrovascular reactivity (CVR) are used to judge the health of the brain vasculature. In this study, we report the use of several different analyses of blood oxygen dependent (BOLD) fMRI responses to CO2 to provide a number of metrics of CVR based on the sigmoidal resistance response to CO2. To assess possible differences in these metrics with age, we compiled atlases reflecting voxel-wise means and standard deviations for four different age ranges and for a group of patients with mild cognitive impairment (MCI) and compared them. Sixty-seven subjects were recruited for this study and scanned at 3T field strength. Of those, 51 healthy control volunteers between the ages of 18–83 were recruited, and 16 (MCI) subjects between the ages of 61–83 were recruited. Testing was carried out using an automated computer-controlled gas blender to induce hypercapnia in a step and ramp paradigm while monitoring end-tidal partial pressures of CO2. Surprisingly, some resistance sigmoid parameters in the oldest control group were increased compared to the youngest control group. Resistance amplitude maps showed increases in clusters within the temporal cortex, thalamus, corpus callosum and brainstem, and resistance reserve maps showed increases in clusters within the cingulate cortex, frontal gyrus, and corpus callosum. These findings suggest that some aspects of vascular reactivity in parts of the brain are initially maintained with age but then may increase in later years. We found significant reductions in all resistance sigmoid parameters (amplitude, reserve, sensitivity, midpoint, and range) when comparing MCI patients to controls. Additionally, in controls and in MCI patients, amplitude, range, reserve, and sensitivity in white matter (WM) was significantly reduced compared to gray matter (GM). WM midpoints were significantly above those of GM. Our general conclusion is that vascular regulation in terms of cerebral blood flow (CBF) responsiveness to CO2 is not significantly affected by age, but is reduced in MCI. These changes in cerebrovascular regulation demonstrate the value of resistance metrics for mapping areas of dysregulated blood flow in individuals with MCI. They may also be of value in the investigation of patients with vascular risk factors at risk for developing vascular dementia.

Sampling reactive regions in phase space by following the minimum dynamic path.

Understanding mechanistic aspects of reactivity lies at the heart of chemistry. Once the potential energy surface (PES) for a system of interest is known, reactions can be studied by computational means. While the minimum energy path (MEP) between two minima of the PES can give some insight into the topological changes required for a reaction to occur, it lacks dynamical information and is an unrealistic depiction of the reactive process. For a more realistic view, molecular dynamics (MD) simulations are required. However, this usually involves generating thousands of trajectories in order to sample a few reactive events and is therefore much more computationally expensive than calculating the MEP. In this work, it is shown that a "minimum dynamic path" (MDP) can be constructed, which, contrary to the MEP, provides insight into the reaction dynamics. It is shown that the underlying concepts can be extended to directly sample reactive regions in phase space. The sampling method and the MDP are demonstrated on the well-known 2-dimensional Müller-Brown PES and for a realistic 12-dimensional reactive PES for sulfurochloridic acid, a proxy molecule used to study vibrationally induced photodissociation of sulfuric acid.

Modeling and analysis of Maxwell nanofluid considering mixed convection and Darcy–Forchheimer relation

This research describes mixed convective Maxwell nanoliquid stretching flow subject to Newtonian heating. Porous medium characteristics are elaborated utilizing non-Darcian relation. Modeling is based on Brownian movement, heat generation, thermophoresis and chemical reaction aspects. Boundary-layer idea is employed for simplification of governing expressions. Optimal homotopy algorithm is implemented for computations of nonlinear problems. Besides, the Sherwood and Nusselt numbers along with temperature, velocity and nanoparticle concentration are analyzed. Our outcomes reveal opposite characteristics for porosity factor and Deborah number against velocity field.

Revealing the Dual Surface Reactions on a HE-NCM Li-Ion Battery Cathode and Their Impact on the Surface Chemistry of the Counter Electrode

The understanding of surface reactions at the electrode-electrolyte interfaces has been a longstanding challenge in Li-ion batteries. X-ray photoemission electron microscopy is used to throw light on the disputed aspects of the surface reactivity of high-energy Li-rich Li1+ x(Ni aCo bMn1- a-b)1- xO2 (HE-NCM) cycled in anaprotic electrolyte against Li4Ti5O12 (LTO). Despite the highly oxidative potential of 5.1 V vs Li+/Li, there is no formation of a layer of oxidized electrolyte byproducts on any of the cathode particles; instead, a homogeneous organic-inorganic layer builds up across the particles of the LTO anode due to the electrolyte and poly(vinylidene fluoride) binder decomposition on HE-NCM. In addition, such a layer incorporates, already from the first charge, micrometer-sized agglomerates of transition metals (TMs). The presence of TMs on the anode is explained by the instability of the reduced Mn, Co, and Ni formed at the surface of HE-NCM mainly during delithiation. The reduced TMs are unstable and prone to be transported to the LTO, where they get further reduced to metallic-like clusters. These results demonstrate that a dual reaction takes place at the HE-NCM-electrolyte interface if subject to high potential, namely, degradation of the surface structure and decomposition of the electrolyte, affecting directly the anode surface through the migration-diffusion processes.

Cytochrome P450-The Wonderful Nanomachine Revealed through Dynamic Simulations of the Catalytic Cycle.

This Account addresses the catalytic cycle of the enzyme cytochrome P450 (CYP450) as a prototypical biological machine with automatic features. CYP450 is a nanomachine that uses dioxygen and two reducing and two proton equivalents to oxidize a plethora of molecules (so-called substrates) as a means of supplying bio-organisms with essential molecules (e.g., brain neurotransmitters, sex hormones, etc.) and protecting biosystems against poisoning. An enticing property of CYP450s is that entrance of an oxidizable substrate into the active site initiates a series of events that constitute the catalytic cycle, which functions "automatically" in a regulated sequence of events culminating in the production of the oxidized substrates (e.g., hydroxylated, epoxidized, etc.), oftentimes with remarkable stereo- and regioselectivities. It is timely to demonstrate how theory uses molecular dynamics (MD) simulations and quantum-mechanical/molecular-mechanical (QM/MM) calculations to complement experiments and elucidate the choreography by which the protein regulates the catalytic cycle. CYP450 is a heme enzyme that contains a ferric ion (FeIII) coordinated by a porphyrin ligand, a water molecule, and a cysteinate ligand that is provided by a strategic residue of the encapsulating protein. While many of the individual steps are sufficiently well-understood, we shall provide here an overview of the factors that cause all of the steps to be sequentially coordinated. To this end, we use examples from three different CYP450 enzymes: the bacterial ones CYP450BM3 and CYP450CAM and the mammalian enzyme CYP4503A4. The treatment is limited to the catalytic cycle, as aspects of two-state reactivity were reviewed previously (e.g., Shaik , S. ; et al. Chem. Rev. 2005 , 105 , 2279 ). What are the principles that govern the seeming automatic feature? For example, how do substrate entrance and binding gate the enzyme? How does the reductase attachment to the enzyme affect the next steps? What triggers the attachment of the reductase? How does the electron transfer (ET) that converts FeIII to FeII occur? Is the ET coordinated with the entrance of O2 into the active site? What is the mechanism of the latter step? Since the entrance of the substrate expels the water molecules from the active site, how do water molecules re-enter to form a proton channel, which is necessary for creating the ultimate oxidant Compound I? How do mutations that disrupt the water channel nevertheless create a competent oxidant? By what means does the enzyme produce regio- and stereoselective oxidation products? What triggers the departure of the oxidized product, and how does the exit occur in a manner that generates the resting state ready for the next cycle? This Account shows that the entrance of the substrate triggers all of the ensuing events.

The role of alexithymia in parent-child interaction and in the emotional ability of children with autism spectrum disorder.

Children with autism spectrum disorder (ASD) have more emotional difficulties than typically developing (TD) children. Of all the factors that impact children's emotional development, parents, and the way they interact with their children, are of crucial importance. The present study compared the amount of parent-child interactions among 35 dyads of parents and their children with ASD and 41 dyads of parents and their TD children, aged between 3 and 13 years, during a frustration-eliciting situation. We further examined whether children's alexithymia is linked to parent-child interactions and whether parent-child interactions are linked to children's emotional difficulties. We found that parents of children with ASD interacted significantly less with their children than parents of TD children. This reduced interaction was better explained by children's alexithymia than by children's ASD diagnosis. Finally, parent-child interaction mediated the relationship between children's ASD diagnosis and children's emotion regulation ability, as well as some aspects of children's emotional reactivity but only if not accounting for children's alexithymia levels. Our results demonstrate the determinant role children's alexithymia plays on parent-child interactions and on how these interactions are linked to children's difficulties in emotion regulation and emotional reactivity. Results are discussed in light of how parent-child interactions and the emotional ability of children with ASD can be improved by targeting children's alexithymia. Autism Res 2019, 12: 458-468 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In the present research, we found that parents of children with autism interact less with their children compared to parents of typically developing children. We also found that this decreased interaction is linked to children's difficulties to recognize, describe, and distinguish emotions, a triad of difficulties known as alexithymia. Furthermore, parents' interaction with their children explains emotional reactivity and emotion regulation problems in children with autism. However, if we take into consideration children's alexithymia, then parents' interaction with their children is not related to their children's emotional difficulties in reactivity and regulation. Therefore, to improve the interaction between parents and their children with autism, and the emotional development of these children, we recommend interventions that teach children with autism how to recognize, describe, and distinguish emotions in themselves and others.

Thermal analysis of nanofluid flow containing gyrotactic microorganisms in bioconvection and second-order slip with convective condition

Bioconvection in magneto-nanoliquid embedded with gyrotactic microorganisms across an elongated sheet with velocity slip of second order is addressed. Nonlinear thermal radiation and chemical reaction aspects are retained in energy and concentration equations. Numerical simulations for the modeled problem are proposed via Runge–Kutta–Fehlberg-based shooting technique. Special attention is given to the impact of involved parameters on the profiles of motile microorganisms, nanoparticle volume fraction, temperature and velocity. Our simulations figured out that assisting flow generates more heat transfer than the opposing flow situation. The motile microorganism’s boundary layer decayed for higher bioconvection Peclet and bioconvection Lewis numbers.

Review of the current status and challenges for a holistic process-based description of mass transport and mineral reactivity in porous media

Reactivity of minerals is controlled by chemical processes at mineral-fluid interfaces acting at different time- and length scales. Various modeling approaches are available to characterize scale-specific aspects of mineral-fluid interface chemistry. Most fundamental aspects of mineral reactivity are provided by atomic scale simulations. Several attempts have been made to interpret macroscopic observation based on atomic scale simulations alone. Many of them have failed however, because of neglecting the pore scale transport phenomena. Pore scale simulation, provide an elegant way to link idealized nanometer scale atomistic description of mineral reactivity with structural and compositional heterogeneities of natural systems. The main challenges are the spatial and temporal coupling of physical models and the upscaling of transport parameters for the macroscopic interpretation of the system behavior. This paper summarizes the current molecular-scale knowledge on mineral-fluid interface chemistry, obtained from complementary coarse-grain simulation approaches. Using the most recent developments in this field, we highlight the complexity and challenges of the pore-scale modeling and suggest a roadmap for the process-based description of mineral dissolution/precipitation across different scales.

Protective Factors Associated with Daily Affective Reactivity and Instability During Adolescence.

The daily emotional experiences of adolescents are dynamic, vary significantly across individuals, and are crucial to their psychological adjustment, warranting a need to identify factors that promote adaptive affective responses to stressors and attenuated affective instability. The objective of this study, therefore, was to examine protective factors linked to individual differences in daily affective reactivity and instability utilizing a daily diary design in a national sample of 100 U.S. adolescents (13-17 years; 40% girls; 79% White). Adolescents completed a baseline survey and then 14 daily online surveys. Better mother-adolescent communication predicted lower negative affect reactivity, whereas greater use of problem-focused coping strategies predicted higher positive affect reactivity. Greater trait resilience and instrumental support seeking predicted lower negative affect instability. Conversely, more emotional support seeking predicted higher negative affect instability. No factors were associated with positive affect instability, and father-adolescent communication was unrelated to daily affective reactivity and instability. The findings implicate specific protective factors associated with distinct aspects of affective reactivity and instability.

Quantum-state-controlled channel branching in cold Ne(3P2)+Ar chemi-ionization.

A prerequisite to gain a complete understanding of the most basic aspects of chemical reactions is the ability to perform experiments with complete control over the reactant degrees of freedom. By controlling these, details of a reaction mechanism can be investigated and ultimately manipulated. Here, we present a study of chemi-ionization-a fundamental energy-transfer reaction-under completely controlled conditions. The collision energy of the reagents was tuned from 0.02 K to 1,000 K, with the orientation of the excited Ne atom relative to Ar fully specified by an external magnetic field. Chemi-ionization of Ne(3P2) and Ar in these conditions enables a detailed investigation of how the reaction proceeds, and provides us with a means to control the branching ratio between the two possible reaction outcomes. The merged-beam experimental technique used here allows access to a low-energy regime in which the atoms dynamically reorient into a favourable configuration for reaction, irrespective of their initial orientations.

Electrochemical Methods for Assessing Kinetic Factors in the Reduction of CO2 to Formate: Implications for Improving Electrocatalyst Design

Thermochemical insights are often employed in the rationalization of reactivity and in the design of electrocatalysts for CO2 reduction reactions targeting C–H bond-containing products. This work identifies experimental methods for assessing kinetic aspects of reactivity. These methods are illustrated using [Fe4N(CO)12]−, which produces formate from CO2 at −1.2 V versus SCE in either a MeCN/H2O solvent (95:5) or pH 6.5 buffered water. Elementary rates for each reaction step are identified along with the rate-determining step (RDS) as C–H bond formation. Transition state kinetics were determined from an Eyring analysis for the rate-determining C–H bond formation step using temperature-dependent electrochemical measurements. A lower measured ΔG⧧ (298 K, 12.3 ± 0.1 kcal mol–1) in a pH 6.5 aqueous solution, compared with a ΔG⧧(298 K) of 15.0 ± 0.1 kcal mol–1 in a MeCN/H2O solvent (95:5), correlates with faster observed reaction rates and provides a kinetic rationalization for the solvent-dependent chemistry. ...

Chemical Reaction Effects on Nano Carreau Liquid Flow Past a Cone and a Wedge with Cattaneo-Christov Heat Flux Model

AbstractChemical reaction aspect is utilized for heat mass transfer analysis of nano non-Newtonian liquid flow past a cone and a wedge. Flow is steady, laminar and two dimensional created due to a cone and a wedge. The Carreau liquid and Cattaneo-Christov heat flux models are utilized. The magneto-nano Carreau liquid material occupies the porous space. The relevant PDEs are rendered into coupled non-linear ODEs via appropriate transformations before treated them numerically through Runge-Kutta and Newton’s method. The computed results are plotted for employing the various values of physical constraints on the profiles of velocity, temperature and nanoparticle volume fraction. Moreover, vitiation of the friction factor, Nusselt number and Sherwood number against physical parameters are presented numerically. It is figured out that convective heating and Brownian motion effects are constructive for thermal boundary layer growth. Aspect of chemical reaction is significant to control the solute layer growth and mass transfer rate.

Sex Matters: Interfering with the Oxidative Stress Response in Pachyonychia Congenita

Pachyonychia congenita is an incurable and often debilitating genodermatosis. Topical application of the antioxidative response inducer sulforaphane, however, alleviates disease symptoms in a murine pachyonychia congenita model, forecasting clinical benefits. The Coulombe laboratory now reports sex-dependent differences in sulforaphane responsiveness of pachyonychia congenita mice, thereby dampening treatment expectations but also unveiling novel aspects of sex-specific oxidative stress reactivity in the epidermis.