Publications by authors named "Jason A Scott"

Article Synopsis
  • Adenylyl cyclase isoform 1 (AC1) is being targeted for new treatments for inflammatory pain, and researchers found a promising group of compounds called pyrazolyl-pyrimidinones that effectively inhibit AC1 but initially had poor solubility in water.
  • The study presented a new approach to enhance the solubility of these compounds by modifying their structure, which led to a more effective version with a strong inhibition value and better solubility.
  • The improved compound showed good absorption in living systems and was effective in reducing pain in a rat model, supporting the idea that inhibiting AC1 could be a viable option for treating chronic pain.
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Bioinspired nanotopography artificially fabricated on titanium surfaces offers a solution for the rising issue of postoperative infections within orthopedics. On a small scale, hydrothermal etching has proven to deliver an effective antimicrobial nanospike surface. However, translation to an industrial setting is limited by the elevated synthesis temperature (150 °C) and associated equipment requirements.

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Ni-based hydroxides are promising electrocatalysts for biomass oxidation reactions, supplanting the oxygen evolution reaction (OER) due to lower overpotentials while producing value-added chemicals. The identification and subsequent engineering of their catalytically active sites are essential to facilitate these anodic reactions. Herein, the proportional relationship between catalysts' deprotonation propensity and Faradic efficiency of 5-hydroxymethylfurfural (5-HMF)-to-2,5 furandicarboxylic acid (FDCA, FE ) is revealed by thorough density functional theory (DFT) simulations and atomic-scale characterizations, including in situ synchrotron diffraction and spectroscopy methods.

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Enhancing the enzymatic activity inside metal-organic frameworks (MOFs) is a critical challenge in chemical technology and bio-technology, which, if addressed, will broaden their scope in energy, food, environmental, and pharmaceutical industries. Here, we report a simple yet versatile and effective strategy to optimize biocatalytic activity by using MOFs to rapidly "lock" the ultrasound (US)-activated but more fragile conformation of metalloenzymes. The results demonstrate that up to 5.

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Transforming natural resources to energy sources, such as converting CH to H and carbon, at high efficiency and low cost is crucial for many industries and environmental sustainability. The high temperature requirement of CH conversion regarding many of the current methods remains a critical bottleneck for their practical uptake. Here we report an approach based on gallium (Ga) liquid metal droplets, Ni(OH) cocatalysts, and mechanical energy input that offers low-temperature and scalable CH conversion into H and carbon.

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Adenylyl cyclase type 1 (AC1) is involved in signaling for chronic pain sensitization in the central nervous system and is an emerging target for the treatment of chronic pain. AC1 and a closely related isoform AC8 are also implicated to have roles in learning and memory signaling processes. Our team has carried out cellular screening for inhibitors of AC1 yielding a pyrazolyl-pyrimidinone scaffold with low micromolar potency against AC1 and selectivity AC8.

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Engineering the metal-carbon heterointerface has become an increasingly important route toward achieving cost-effective and high-performing electrocatalysts. The specific properties of graphene edge sites, such as the high available density of states and extended unpaired π-bonding, make it a promising candidate to tune the electronic properties of metal catalysts. However, to date, understanding and leveraging graphene edge-metal catalysts for improved electrocatalytic performance remains largely elusive.

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The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure.

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Fish are particularly sensitive to aryl hydrocarbon receptor (AhR)-mediated developmental toxicity. The molecular mechanisms behind these adverse effects have remained largely unresolved in salmonids, and for AhR-agonistic polycyclic aromatic hydrocarbons (PAHs). This study explored the cardiac transcriptome of rainbow trout (Oncorhynchus mykiss) eleuteroembryos exposed to retene, an AhR-agonistic PAH.

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Objective: Emerging evidence suggests that methionine oxidation can directly affect protein function and may be linked to cardiovascular disease. The objective of this study was to define the role of the methionine sulfoxide reductase A (MsrA) in models of vascular disease and identify its signaling pathways.

Approach And Results: MsrA was readily identified in all layers of the vascular wall in human and murine arteries.

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A silica-based mesoporous nanosphere (MSN) controlled-release drug delivery system has been synthesized and characterized. The system uses l-cysteine derivatized gold nanoparticles (AuNPs), bound to the MSNs using Cu as a bridging ion. The AuNPs serve as removable caps that hinder the release of drug molecules inside the amino functionalized MSN mesoporous framework.

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Activation of the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and reactive oxygen species (ROS) promote neointimal hyperplasia after vascular injury. CaMKII can be directly activated by ROS through oxidation. In this study, we determined whether abolishing the oxidative activation site of CaMKII alters vascular smooth muscle cell (VCMC) proliferation, migration and apoptosis in vitro and neointimal formation in vivo.

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Objective: Sustained hemodynamic stress mediated by high blood flow promotes arteriogenesis, the outward remodeling of existing arteries. Here, we examined whether Ca²⁺/calmodulin-dependent kinase II (CaMKII) regulates arteriogenesis.

Methods And Results: Ligation of the left common carotid led to an increase in vessel diameter and perimeter of internal and external elastic lamina in the contralateral, right common carotid.

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Increased reactive oxygen species (ROS) contribute to asthma, but little is known about the molecular mechanisms connecting increased ROS with characteristic features of asthma. We show that enhanced oxidative activation of the Ca(2+)/calmodulin-dependent protein kinase (ox-CaMKII) in bronchial epithelium positively correlates with asthma severity and that epithelial ox-CaMKII increases in response to inhaled allergens in patients. We used mouse models of allergic airway disease induced by ovalbumin (OVA) or Aspergillus fumigatus (Asp) and found that bronchial epithelial ox-CaMKII was required to increase a ROS- and picrotoxin-sensitive Cl(-) current (ICl) and MUC5AC expression, upstream events in asthma progression.

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The multifunctional CaMKII has been implicated in vascular smooth muscle cell (VSMC) migration, but little is known regarding its downstream targets that mediate migration. Here, we examined whether CaMKII regulates migration through modulation of matrix metalloproteinase 9 (MMP9). Using CaMKIIδ(-/-) mice as a model system, we evaluated migration and MMP9 regulation in vitro and in vivo.

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The field of heterogeneous photocatalysis has expanded rapidly in the last four decades, having undergone various evolutionary phases related to energy and the environment. The two most significant applications of photocatalysis are geared toward solar water splitting and the purification of air and water. Notably, the interdisciplinary nature of the field has increased significantly, incorporating semiconductor physics, surface sciences, photo and physical chemistry, materials science, and chemical engineering.

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The microbial transformation of arsenic species in municipal landfill leachate (MLL) was investigated with the objective to highlight arsenic transformation in the landfill system. Across the 43 day incubation in MLL, more than 90% arsenate (iAs(V)) was found to reduce to arsenite (iAs(III)) within 20 days, while iAs(III) was comparably stable although a fraction of iAs(III) was temporarily oxidated to iAs(V) in the first 3 days. Transformation of monomethylarsonic acid (MMA(V)) to dimethylarsinic acid (DMA(V)) in MLL was slow with only 5% MMA(V) methylated to DMA(V) after 43 days incubation.

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In the embryo-larval stages of fish, alkylphenanthrenes such as retene (7-isopropyl-1-methylphenanthrene) produce a suite of developmental abnormalities typical of exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including pericardial and yolk sac edema, cardiovascular dysfunction, and skeletal deformities. To investigate the mechanism and target tissue of retene toxicity, we used observational, histological, and protein knockdown techniques in zebrafish (Danio rerio) embryos. The primary overt signs of toxicity are pericardial edema and reduced blood flow, first observed at 36 h post-fertilization (hpf).

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National Health and Nutrition Examination Survey data show an association between hypertension and exposure to dioxin-like halogenated aromatic hydrocarbons (HAHs). Furthermore, chronic exposure of mice to the prototypical HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces reactive oxygen species (ROS), endothelial dysfunction, and hypertension. Because TCDD induces cytochrome P4501A1 (CYP1A1) and CYP1A1 can increase ROS, we tested the hypothesis that TCDD-induced endothelial dysfunction and hypertension are mediated by CYP1A1.

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Arsenic species in municipal landfill leachates (MLL) were investigated by HPLC-DRC-ICPMS and LC-ESI-MS/MS. Various arsenic species including arsenate (iAs(V)), arsenite (iAs(III)), monomethylarsonic acid (MMA(V)), dimethylarsinic acid (DMA(V)), as well as sulfur-containing organoarsenic species were detected. Two sulfur-containing arsenic species in a MLL were positively identified as dimethyldithioarsinic acid (DMDTA(V)) and dimethylmonothioarsinic acid (DMMTA(V)) by comparing their molecular ions, fragment patterns and sulfur/arsenic ratios with in-house synthesised thiol-organoarsenic compounds.

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It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr(-/-)) mice may alter cardiovascular homeostasis in adulthood. We tested the hypothesis that blood pressure regulation in adult heterozygous mice (ahr(+/-)) would be normal, compared to ahr(-/-) mice, since no vascular abnormalities have been reported in the heterozygote animals. Mean arterial blood pressure (MAP) was measured using radiotelemetry prior to and during treatment with inhibitors of the autonomic nervous system, nitric oxide synthase (NOS), angiotensin converting enzyme (ACE), or endothelin-1 A receptor (ET(A)).

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Environmentally relevant mixtures of polycyclic aromatic hydrocarbons (PAHs; e.g., crude oils) are often rich in alkyl-PAHs, such as retene (7-isopropyl-1-methylphenanthrene), which produce dioxin-like toxicity in fish embryos.

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Diesel is a complex mixture containing polycyclic aromatic hydrocarbons, which persist after a spill, pass readily from water into tissues, and are toxic to early life stages of fish. The bioavailability and chronic toxicity of hydrocarbons dissolved into water from floating diesel (water-accommodated fraction) and chemically dispersed diesel (chemically enhanced water-accommodated fraction) were measured by the extent of ethoxyresorufin-O-deethylase (EROD) induction in juvenile rainbow trout (Oncorhynchus mykiss) and by the severity of blue sac disease in embryos. The water-accommodated fraction of floating diesel was virtually nontoxic to embryos at nominal concentrations up to 1,000 mg/L, causing only small weight changes.

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Alkylated polycyclic aromatic hydrocarbons, such as retene (7-isopropyl-1-methylphenanthrene), induce cytochrome P450 1A (CYP1A) enzymes and produce dioxin-like toxicity in the embryo-larval stages of fish characterized by the signs of blue sac disease (BSD). The signs of toxicity are well characterized; however, the mechanism is not well understood. To elucidate the role of CYP1A in retene toxicity, larval rainbow trout (Oncorhynchus mykiss) were co-treated with a range of concentrations of alpha-naphthoflavone (ANF), a known CYP1A inhibitor.

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The function of iron (ferric (Fe(III)) and ferrous (Fe(II))) in the hexavalent chromium (Cr(VI)) reduction mechanism by bacteria in municipal landfill leachate (MLL) was assessed. Evidence of an "electron shuttle" mechanism was observed, whereby the Cr(VI) was reduced to trivalent chromium (Cr(III)) by Fe(II) with the resulting Fe(III) bacterially re-reduced to Fe(II). Typically, investigations on this electron shuttle mechanism have been performed in an artificial medium.

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