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NPJ Biofilms and Microbiomes Nov 2020The core of the chemotaxis system of Shewanella oneidensis is made of the CheA3 kinase and the CheY3 regulator. When appropriated, CheA3 phosphorylates CheY3, which, in...
The core of the chemotaxis system of Shewanella oneidensis is made of the CheA3 kinase and the CheY3 regulator. When appropriated, CheA3 phosphorylates CheY3, which, in turn, binds to the rotor of the flagellum to modify the swimming direction. In this study, we showed that phosphorylated CheY3 (CheY3-P) also plays an essential role during biogenesis of the solid-surface-associated biofilm (SSA-biofilm). Indeed, in a ΔcheY3 strain, the formation of this biofilm is abolished. Using the phospho-mimetic CheY3D56E mutant, we showed that CheY-P is required throughout the biogenesis of the biofilm but CheY3 phosphorylation is independent of CheA3 during this process. We have recently found that CheY3 interacts with two diguanylate cyclases (DGCs) and with MxdA, the c-di-GMP effector, probably triggering exopolysaccharide synthesis by the Mxd machinery. Here, we discovered two additional DGCs involved in SSA-biofilm development and showed that one of them interacts with CheY3. We therefore propose that CheY3-P acts together with DGCs to control SSA-biofilm formation. Interestingly, two orthologous CheY regulators complement the biofilm defect of a ΔcheY3 strain, supporting the idea that biofilm formation could involve CheY regulators in other bacteria.
Topics: Anabasine; Bacterial Proteins; Biofilms; Chemotaxis; Escherichia coli Proteins; Flagella; Gene Expression Regulation, Bacterial; Methyl-Accepting Chemotaxis Proteins; Mutation; Nicotine; Phosphorus-Oxygen Lyases; Phosphorylation; Shewanella
PubMed: 33188190
DOI: 10.1038/s41522-020-00165-5 -
BMC Ecology Nov 2020Invasive plant species pose a significant threat for fragile isolated ecosystems, occupying space, and consuming scarce local resources. Recently though, an additional...
BACKGROUND
Invasive plant species pose a significant threat for fragile isolated ecosystems, occupying space, and consuming scarce local resources. Recently though, an additional adverse effect was recognized in the form of its secondary metabolites entering the food chain. The present study is elaborating on this subject with a specific focus on the Nicotiana glauca Graham (Solanaceae) alkaloids and their occurrence and food chain penetrability in Mediterranean ecosystems. For this purpose, a targeted liquid chromatography electrospray tandem mass spectrometric (LC-ESI-MS/MS) analytical method, encompassing six alkaloids and one coumarin derivative, utilizing hydrophilic interaction chromatography (HILIC) was developed and validated.
RESULTS
The method exhibited satisfactory recoveries, for all analytes, ranging from 75 to 93%, and acceptable repeatability and reproducibility. Four compounds (anabasine, anatabine, nornicotine, and scopoletin) were identified and quantified in 3 N. glauca flowers extracts, establishing them as potential sources of alien bio-molecules. The most abundant constituent was anabasine, determined at 3900 μg/g in the methanolic extract. These extracts were utilized as feeding treatments on Apis mellifera honeybees, resulting in mild toxicity documented by 16-18% mortality. A slightly increased effect was elicited by the methanolic extract containing anabasine at 20 μg/mL, where mortality approached 25%. Dead bees were screened for residues of the N. glauca flower extracts compounds and a significant mean concentration of anabasine was evidenced in both 10 and 20 μg/mL treatments, ranging from 51 to 92 ng/g per bee body weight. Scopoletin was also detected in trace amounts.
CONCLUSIONS
The mild toxicity of the extracts in conjunction with the alkaloid and coumarin residual detection in bees, suggest that these alien bio-molecules are transferred within the food chain, suggesting a chemical invasion phenomenon, never reported before.
Topics: Alkaloids; Animals; Bees; Ecosystem; Reproducibility of Results; Tandem Mass Spectrometry; Nicotiana
PubMed: 33158433
DOI: 10.1186/s12898-020-00325-3 -
Ingestion of A Common Plant's Leaves Leads to Acute Respiratory Arrest and Paralysis: A Case Report.Clinical Practice and Cases in... Aug 2020Nicotiana glauca is a plant known to cause acute toxicity upon ingestion or dermal exposure due to the nicotinic alkaloid, anabasine. Nicotinic alkaloids cause toxicity...
BACKGROUND
Nicotiana glauca is a plant known to cause acute toxicity upon ingestion or dermal exposure due to the nicotinic alkaloid, anabasine. Nicotinic alkaloids cause toxicity by acting as agonists on nicotinic-type acetylcholine receptors (nAChRs). Initial stimulation of these receptors leads to symptoms such as tachycardia, miosis, and tremors. The effects of high doses of nicotinic alkaloids are biphasic, and eventual persistent depolarization of nAChRs at the neuromuscular junction occurs. This causes apnea, paralysis, and cardiovascular collapse.
CASE REPORT
In this report, we present a case of respiratory arrest due to nicotinic alkaloid poisoning from the ingestion of Nicotiana glauca. The diagnosis was suspected after the patient's family gave a history of the patient ingesting a plant prior to arrival. They were able to also provide a physical sample of the plant.
CONCLUSION
The phone application, "Plant Snap", determined the plant species and helped confirm the diagnosis. This case describes how modern technology and thorough history taking can combine to provide the best possible patient care.
PubMed: 32926689
DOI: 10.5811/cpcem.2020.5.46703 -
Environment International Dec 2020Measurement of population tobacco use via wastewater-based epidemiology (WBE) provides objective data to evaluate the efficacy of tobacco control strategies. However,...
Measurement of population tobacco use via wastewater-based epidemiology (WBE) provides objective data to evaluate the efficacy of tobacco control strategies. However, current WBE tobacco-use estimates based on nicotine metabolites (cotinine and hydroxycotinine) can be masked by use of non-tobacco nicotine-containing products. To better understand nicotine and tobacco use, we analysed tobacco-specific biomarkers, anabasine and anatabine, as well as nicotine metabolites, cotinine and hydroxycotinine, in wastewater samples collected for 6 weeks per year over 6 years (2012-2017) from an Australian wastewater treatment plant serving approximately 100,000 people. Population-normalised mass loads were used to estimate tobacco and nicotine use trends and were compared with surveys and taxation statistics. Significant annual declines were observed for anabasine, anatabine, cotinine and hydroxycotinine of -3.0%, -2.7%, -2.4%, and -2.1%, respectively. The results corresponded with the annual declining trends reported from surveys (-5%) and taxation statistics (-4%). Significant annual decreases in the ratios of anabasine to cotinine (-1.2%) and anatabine to cotinine (-1.0%) suggested a relative increase in the use of non-tobacco nicotine products at the same time that tobacco use was declining. Monitoring tobacco use with anabasine and anatabine removed influence from nicotine-containing products, showing larger reductions in this Australian city than via nicotine biomarkers, whilst also demonstrating their suitability for monitoring long-term trends.
Topics: Anabasine; Australia; Cotinine; Humans; Nicotine; Nicotiana; Tobacco Use; Wastewater-Based Epidemiological Monitoring
PubMed: 32911244
DOI: 10.1016/j.envint.2020.106088 -
BMC Plant Biology Jun 2020Nicotine is a stimulant and potent parasympathomimetic alkaloid that accounts for 96-98% of alkaloid content. A reduction in the amount of nicotine in cigarettes to...
BACKGROUND
Nicotine is a stimulant and potent parasympathomimetic alkaloid that accounts for 96-98% of alkaloid content. A reduction in the amount of nicotine in cigarettes to achieve a non-addictive level is necessary. We investigated whether replacing tobacco root with eggplant by grafting can restrict nicotine biosynthesis and produce tobacco leaves with ultra-low nicotine content, and analyzed the gene expression differences induced by eggplant grafting.
RESULTS
The nicotine levels of grafted tobacco leaves decreased dramatically. The contents of nornicotine, anabasine, NNN, NNK, NAT, total TSNAs and the nicotine of mainstream cigarette smoke decreased, and the contents of amino acids and the precursors of alkaloids increased in grafted tobacco. Eggplant grafting resulted in the differential expression of 440 genes. LOC107774053 had higher degrees in two PPI networks, which were regulated by LOC107802531 and LOC107828746 in the TF-target network.
CONCLUSIONS
Replacing tobacco root with eggplant by grafting can restrict nicotine biosynthesis and produce tobacco leaves with ultra-low or zero nicotine content. The differential expression of LOC107774053 may be associated with eggplant grafting.
Topics: Nicotine; Smoke; Solanum melongena; Nicotiana
PubMed: 32571218
DOI: 10.1186/s12870-020-02459-4 -
Phytochemistry Sep 2020In this study, we determined the pyridine alkaloid content (nicotine, nornicotine, anabasine, anatabine, cotinine, and myosmine) of 58 species and 2 subspecies of the...
In this study, we determined the pyridine alkaloid content (nicotine, nornicotine, anabasine, anatabine, cotinine, and myosmine) of 58 species and 2 subspecies of the Nicotiana genus by ultra-high-performance liquid chromatography coupled with mass spectrometry. We observed clear correlation between Noctiflorae and Suaveolentes sections and their above average accumulation of anabasine in the genus. In addition, the results demonstrated the presence of not only trace amounts but quantifiable levels of myosmine, an alkaloid previously detected in only minute quantities, in the leaves and roots of 16 species. In this study, analysis of gene expression of 58 species and 2 subspecies from the Nicotiana genus by mRNA sequencing was performed for the first time. Sequencing reads were mapped against annotated genes of a Nicotiana tabacum reference genome and expression values were subsequently calculated. Hierarchical clustering of alkaloid biosynthesis pathway genes and alkaloid content composition revealed patterns clearly segregating Nicotiana sections. Correlation of gene expression with alkaloid accumulation phenotypes was evident, including low putrescine methyltransferase expression for all species in the Suaveolentes section or clear correlation of nicotine demethylase with conversion rates of nicotine to nornicotine in the majority of species. Multiple additional correlations between alkaloid accumulation and gene expression values were identified, which makes this study an important fundament toward future scientific exploration of the Nicotiana genus.
Topics: Alkaloids; Anabasine; Plant Leaves; Nicotiana; Transcriptome
PubMed: 32526514
DOI: 10.1016/j.phytochem.2020.112424 -
Frontiers in Chemistry 2020Anabasine (ANA), a major piperidine alkaloid originally isolated from wild tobacco trees (), has been known to induce serious developmental toxicities such as skeletal...
Anabasine (ANA), a major piperidine alkaloid originally isolated from wild tobacco trees (), has been known to induce serious developmental toxicities such as skeletal deformities in livestock and humans. In this study, we thoroughly investigated the supramolecular nano-encapsulations of ANA by an artificial nanocontainer, cucurbit[7] uril (CB[7]), and examined the influences of the nano-encapsulation on ANA's inherent developmental toxicities on a zebrafish model. We have shown that CB[7] formed 1:1 host-guest inclusion complexes with ANA via a relatively high binding strength [ of (7.45 ± 0.31) × 10 M] in an aqueous solution, via UV-vis and H nuclear magnetic resonance spectroscopic titrations, as well as isothermal titration calorimetry titration. As a consequence, CB[7] significantly attenuated the developmental toxicity of ANA on zebrafish . In contrast, for a comparative purpose, β-CD didn't exert any influence on the toxicity of ANA due to its weak binding with ANA, which was not even measurable via either spectroscopic methods or ITC titration. This is the first head-to-head comparison of this pair of nanocontainers, CB[7] and β-CD, on their potential roles in influencing the toxicity of guest molecules and the results suggested that CB[7] could become a more promising functional excipient for reducing the inherent toxicities of active pharmaceutical ingredients, particularly alkaloids that may form relatively strong host-guest binding species with the host.
PubMed: 32185162
DOI: 10.3389/fchem.2020.00134 -
Trials Feb 2020Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking...
BACKGROUND
Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit?
METHODS
The Cessation in Pregnancy Incentives Trial (CPIT) III is a pragmatic, 42-month, multi-centre, parallel-group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual Stop Smoking Services (SSS) support, the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy. Participants (n = 940) are pregnant smokers (age > 16 years, < 24 weeks pregnant, English speaking), who consent via telephone to take part and are willing to be followed-up in late pregnancy and 6 months after birth. The primary outcome is cotinine/anabasine-validated abstinence from smoking in late pregnancy. Secondary outcomes include engagement with SSS, quit rates at 4 weeks from agreed quit date and 6 months after birth, and birth weight. Outcomes will be analysed by intention to treat, and regression models will be used to compare treatment effects on outcomes. A meta-analysis will include data from the feasibility study in Glasgow. An economic evaluation will assess cost-effectiveness from a UK NHS perspective. Process evaluation using a case-study approach will identify opportunities to improve recruitment and learning for future implementation. Research questions include: what is the therapeutic efficacy of incentives; are incentives cost-effective; and what are the potential facilitators and barriers to implementing incentives in different parts of the UK?
DISCUSSION
This phase III trial in Scotland, England and Northern Ireland follows a successful phase II trial in Glasgow, UK. The participating sites have diverse SSS that represent most cessation services in the UK and serve demographically varied populations. If found to be acceptable and cost-effective, this trial could demonstrate that financial incentives are effective and transferable to most UK SSS for pregnant women.
TRIAL REGISTRATION
Current Controlled Trials, ISRCTN15236311. Registered on 9 October 2017.
Topics: Adolescent; Adult; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; England; Equivalence Trials as Topic; Female; Financial Support; Follow-Up Studies; Humans; Motivation; Multicenter Studies as Topic; Northern Ireland; Pragmatic Clinical Trials as Topic; Pregnancy; Prenatal Care; Randomized Controlled Trials as Topic; Scotland; Smoking; Smoking Cessation; State Medicine; Young Adult
PubMed: 32059684
DOI: 10.1186/s13063-019-4042-8 -
Marine Drugs Feb 2020Many organisms possess "secondary" compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more...
Many organisms possess "secondary" compounds to avoid consumption or to immobilize prey. While the most abundant or active compounds are initially investigated, more extensive analyses reveal other "minor" compounds with distinctive properties that may also be of biomedical and pharmaceutical significance. Here, we present an initial in vitro investigation of the actions of two isomeric tetrahydropyridyl ring-containing anabasine analogs: isoanatabine, an alkaloid isolated from a marine worm, and anatabine, a relatively abundant minor alkaloid in commercial tobacco plants. Both compounds have a double bond that is distal to the piperidine ring nitrogen of anabasine. Racemic isoanatabine and anatabine were synthesized and their S- and R-enantiomers were isolated by chiral high pressure liquid chromatography (HPLC). Both isoanatabines displayed higher efficacies at α4β2 nicotinic acetylcholine receptors (nAChRs) relative to the anatabines; R-isoanatabine was most potent. Radioligand binding experiments revealed similar α4β2 nAChR binding affinities for the isoanatabines, but R-anatabine affinity was twice that of S-anatabine. While the two anatabines and S-isoanatabine were highly efficacious agonists at α7 nAChRs, R-isoanatabine was only a weak partial agonist. The four compounds share an ability to stimulate both α4β2 and α7 nAChRs, a property that may be useful in developing more efficacious drugs to treat neurodegenerative and other medical disorders.
Topics: Alkaloids; Anabasine; Animals; Humans; Isomerism; Marine Toxins; Nicotine; Nicotinic Agonists; Pyridines; Receptors, Nicotinic; Nicotiana; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 32053997
DOI: 10.3390/md18020106 -
Phytochemistry Feb 2020Nicotinic acetylcholine receptor (nAChR) subtype-selective pharmacological profiles of tobacco alkaloids are essential for understanding the physiological effects of...
Nicotinic acetylcholine receptor (nAChR) subtype-selective pharmacological profiles of tobacco alkaloids are essential for understanding the physiological effects of tobacco products. In this study, automated electrophysiology was used to functionally characterize the effects of distinct groups of tobacco alkaloids on human α4β2 and α7 nAChRs. We found that, in tobacco alkaloids, pyridine as a hydrogen bond acceptor and a basic nitrogen atom at a distance of 4-7 Å are pharmacophoric elements necessary for molecular recognition by α4β2 and α7 nAChRs with various degrees of selectivity, potency, and efficacy. While four alkaloids-nicotine, nornicotine, anabasine and R-anatabine-potently activated α4β2, they were also weak agonists of α7 nAChRs. Nicotine was the most potent agonist of α4β2, while anabasine elicited the highest activation of α7. None of the tobacco alkaloids enhanced nAChR activity elicited by the endogenous ligand acetylcholine; therefore, none was considered to be a positive allosteric modulator (PAM) of either α4β2 or α7 nAChRs. In contrast, we identified tobacco alkaloids, such as the tryptophan metabolite 6-hydroxykynurenic acid, that decreased the activity of both α4β2 and α7 nAChRs. Our study identified a class of alkaloids with positive and negative effects against human α4β2 and α7 nAChRs. It also revealed human α4β2 to be the principal receptor for sensing the most abundant alkaloids in tobacco leaves.
Topics: Alkaloids; Biological Products; Dose-Response Relationship, Drug; Humans; Ligands; Molecular Structure; Phytochemicals; Receptors, Nicotinic; Structure-Activity Relationship; Nicotiana; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 31865001
DOI: 10.1016/j.phytochem.2019.112187