Biology subjects

Wilde, S.

Publications and source records attributed to Wilde, S..

5 recordsLinked to original sources

bioRxiv2026

The collective effect of non-nicotine constituents on the reinforcing and neuropharmacological effects of comprehensive cigarette smoke and electronic nicotine delivery system (ENDS) aerosol extracts in rats.

Tobacco product extracts containing nicotine and non-nicotine constituents are useful for understanding the collective role of these constituents in tobacco use disorder (TUD). However, few studies have used extracts with both water-soluble and non-water-soluble constituents with accompanying chemical analysis, or compared behavioral and neuropharmacological effects across product types. To address these limitations, we compared the relative abuse liability of cigarette smoke (CS) and electronic nicotine delivery system (ENDS) aerosol (EA) extracts to nicotine alone using intravenous self-administration in rats, and examined effects on nucleus accumbens (NAc) dopamine (DA) release and binding/function at nicotinic acetylcholine receptors (nAChRs) and other addiction-related receptors in vitro. CS extract contained higher levels of several behaviorally active non-nicotine constituents than EA extract. Both extracts produced a downward/leftward shift in the descending limb of the unit dose-response curve relative to nicotine alone, while only CS extract produced greater compensatory increases in responding compared to nicotine alone. Demand intensity (Q0) was lower for CS but not EA extract, relative to nicotine alone, whereas demand elasticity for both extracts was similar to nicotine alone. Stress-induced reinstatement was comparable between CS extract and nicotine alone but attenuated for EA extract. CS extract, but not EA extract, showed greater potency for 4{beta}2 nAChR activation and substantial binding across numerous non-nAChRs (DA, serotonergic, opioid) relative to nicotine alone at a high screening concentration. CS extract, but not nicotine alone, also inhibited cyclooxygenase (COX)-1 and -2 at smoking-relevant concentrations. There was no difference in NAc DA release between formulations. These findings indicate non-nicotine constituents contribute to certain reinforcing and neuropharmacological effects of CS, and to a lesser extent EA. Our finding of COX inhibition by CS extract warrants further investigation as a potential mechanism contributing to the effects of CS and TUD.

pharmacology and toxicology↗

bioRxiv2024

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination

Background{beta}-Nicotyrine ({beta}-Nic) is a unique minor alkaloid constituent in electronic nicotine delivery systems (ENDS) that is derived from nicotine (Nic) degradation and can reach 25% of Nic concentrations in ENDS aerosol. {beta}-Nic slows Nic metabolism and prolongs systemic Nic exposure, which may alter the discriminability of Nic. The present study sought to examine {beta}-Nic has interoceptive effects itself, and if it alters the subjective effects ENDS products within a drug-discrimination paradigm. MethodsThe pharmacodynamics of {beta}-Nic were examined in vitro, and a nicotine discrimination paradigm was used to determine if {beta}-Nic (0 - 5.0 mg/kg) shares discriminative stimulus properties with Nic (0.2 mg/kg) in male (n = 13) and female (n = 14) rats after 10- & 60-min {beta}-Nic pretreatment delays. A second group of rats was trained to discriminate {beta}-Nic and Nornicotine (Nornic) from saline to determine if {beta}-Nic alone has interoceptive properties and whether they are similar to Nornic. Results{beta}-Nic had similar binding affinity and efficacy at the 4{beta}2 nicotinic receptor subtype as Nornic, [~]50% of Nic efficacy. However, {beta}-Nic only weakly substituted for Nic during substitution testing in female rats, but not males, whereas Nornic fully substituted for Nic. Combination testing at the 10 and 60-min pretreatment intervals showed that {beta}-Nic dose-dependently increased the duration of nicotines discriminative stimulus effects, especially at the 60-min delay. Drug naive rats could reliably discriminate Nornic, but not {beta}-Nic, from Sal. Conclusion{beta}-Nic increased and prolonged the interoceptive stimulus properties of Nic, suggesting it may alter to the abuse liability of ENDS through its ability to slow Nic metabolism.

pharmacology and toxicology↗

bioRxiv2020

Validation of Functional Polymorphisms Affecting Maize Plant Height by Unoccupied Aerial Systems (UAS) allows Novel Temporal Phenotypes

Plant height (PHT) in maize (Zea mays L.) has been scrutinized genetically and phenotypically due to relationship with other agronomically valuable traits (e.g. yield). Heritable variation of PHT is determined by many discovered quantitative trait loci (QTLs); however, phenotypic effects of such loci often lack validation across environments and genetic backgrounds, especially in the hybrid state grown by farmers rather than the inbred state preferred by geneticists. A previous genome wide association study using a hybrid diversity panel identified two novel quantitative trait variants (QTVs) controlling both PHT and grain yield. Here, heterogeneous inbred families demonstrated that these two loci, characterized by two single nucleotide polymorphisms (SNPs), cause phenotypic variation in inbred lines, but that size of these effects were variable across four different genetic backgrounds, ranging from 1 to 10 cm. Weekly unoccupied aerial system flights demonstrated both SNPs had larger effects, varying from 10 to 25 cm, in early growth while SNPs effects decreased towards the end of the season. These results show that allelic effect sizes of economically valuable loci are both dynamic in temporal growth and dynamic across genetic backgrounds resulting in informative phenotypic variability overlooked following traditional phenotyping methods. Public genotyping data shows recent favorably selection in elite temperate germplasm with little change across tropical backgrounds. As these loci remain rare in tropical germplasm, with effects most visible early in growth, they are useful for breeding and selection to expand the genetic basis of maize.

plant biology↗

bioRxiv2020

Group A Streptococcus Infection of the Nasopharynx Requires Proinflammatory Signaling Through the Interleukin-1 Receptor

Group A Streptococcus (GAS) is the etiologic agent of numerous high morbidity and high mortality diseases which commonly have a highly proinflammatory pathology. One factor contributing to this inflammation is the GAS protease SpeB, which directly activates the proinflammatory cytokine interleukin-1{beta} (IL-1{beta}), independent of the canonical inflammasome pathway. IL-1{beta} drives neutrophil activation and recruitment that limits bacterial growth and invasion during invasive skin and soft tissue infections like necrotizing fasciitis. GAS also causes pharyngitis (strep throat), and the upper respiratory tract is its primary nidus for growth and transmission. Since the fitness selection for the species is likely primarily for this site, we examined the process of IL-1{beta} activation in the murine nasopharynx. SpeB still activated IL-1{beta}, which was required for neutrophil migration, but this inflammation instead increased GAS replication. Inhibiting IL-1{beta} or depleting neutrophils, which both promote invasive infection, prevented GAS infection of the nasopharynx. Prior antibiotic exposure increased GAS growth in the murine nasopharynx, and antibiotics were sufficient to reverse the attenuation previously observed when IL-1{beta}, neutrophils, or SpeB were not present to drive inflammation. Therefore, the same fundamental mechanism has opposing effects on virulence at different body sites. Invasive disease may be limited in part due to specific adaptations for inducing host inflammation that are beneficial for pharyngitis. IMPORTANCEOur previous reports showed that Group A Streptococcus (GAS) protease SpeB directly activates the host proinflammatory cytokine IL-1{beta} and this restricts invasive skin infection. The upper respiratory tract is the primary site of GAS colonization and infection, but the host-pathogen interactions at this site are still largely unknown. We provide the first evidence that IL-1{beta}-mediated inflammation promotes upper respiratory tract infection. This provides experimental evidence that the notable inflammation of strep throat, which presents with significant swelling, pain, and neutrophil influx, is not an ineffectual immune response, but rather is a GAS-directed remodeling of this niche for its pathogenic benefit.

microbiology↗

bioRxiv2018

Salmonella-vectored vaccine delivering three Clostridium perfringens antigens protects poultry against necrotic enteritis.

Necrotic enteritis is an economically important poultry disease caused by the bacterium Clostridium perfringens. There are currently no necrotic enteritis vaccines available for use in broiler birds, the most important target population. Salmonella-vectored vaccines represent a convenient and effective option for controlling this disease. We used a single attenuated Salmonella vaccine strain, engineered to lyse within the host, to deliver up to three C. perfringens antigens. Two of the antigens were toxoids, based on C. perfringens -toxin and NetB toxin. The third antigen was fructose-1,6-bisphosphate aldolase (Fba), an metabolic enzyme with an unknown role in virulence. Oral immunization with a single Salmonella vaccine strain producing either Fba, -toxoid and NetB toxoid, or all three antigens, was immunogenic, inducing serum, cellular and mucosal responses against Salmonella and the vectored C. perfringens antigens. All three vaccine strains were protective against virulent C. perfringens challenge. The strains delivering Fba only or all three antigens provided the best protection. We also demonstrate that both toxins and Fba are present on the C. perfringens cell surface. The presence of Fba on the cell surface suggests that Fba may function as an adhesin.

microbiology↗