ABSTRACT
Understanding how bacterial community assembly and antibiotic resistance genes (ARGs) respond to antibiotic exposure is essential to deciphering the ecological risk of anthropogenic antibiotic pollution in soils. In this study, three loam soils with different land management (unmanured golf course, dairy-manured pasture, and swine-manured cornfield) were spiked with a mixture of 11 antibiotics at the initial concentration of 100 and 1000 µg kg-1 for each antibiotic and incubated over 132 days, mimicking a scenario of pulse disturbance and recovery in soils, with unspiked soil samples as the control treatment. The Infer Community Assembly Mechanisms by Phylogenetic-bin-based null model (iCAMP) analysis demonstrated that drift and dispersal limitation contributed to 57%-65% and 16%-25%, and homogeneous selection 12%-16% of soil bacterial community assembly. Interestingly, antibiotic exposure to 1000 µg kg-1 level significantly increased the contribution of drift to community assembly, largely due to the positive response from Acidobacteria-6 in the golf course and pasture soils and from Chthoniobacteraceae in the cornfield soil to the antibiotic exposure. However, ARG abundance and diversity in the three soils exhibited antibiotics-independent temporal fluctuations, but were associated with the changes in soil bacterial communities over time. This study provides the first insight into the relative contributions of different bacterial community assembly processes in soils upon antibiotic exposure at environmentally relevant concentrations.
Subject(s)
Anti-Bacterial Agents , Soil , Animals , Swine , Anti-Bacterial Agents/pharmacology , Genes, Bacterial/genetics , Phylogeny , Bacteria/genetics , Drug Resistance, Microbial/genetics , Manure/analysis , Soil MicrobiologyABSTRACT
Predicting plant uptake of pharmaceuticals from soils is very challenging because many pharmaceuticals are ionizable compounds, which experience highly variable sorption/desorption and transformation processes in soils. This study aimed to elucidate how the equilibrium between sorbed and dissolved phases influences radish uptake of 15 pharmaceuticals from three soils with different properties. After 30 days of uptake, the accumulation of acetaminophen, carbamazepine, lamotrigine, carbadox, trimethoprim, and triclosan in radish ranked as Riddles > Capac > Spinks soil. In contrast, radish accumulation of caffeine, lincomycin, monensin, tylosin, sulfadiazine, and sulfamethoxazole exhibited the opposite order of Riddles < Capac < Spinks soil. Oxytetracycline and estrone demonstrated similar accumulation in radish grown in the three soils. Accumulation of pharmaceuticals in radish demonstrated no apparent relation with their concentration in soils. However, we identified strong positive correlation between pharmaceutical accumulation in radish and their corresponding concentration in soil pore water. These results reveal that pharmaceutical in soil pore water is the dominant fraction bioavailable to plant uptake. Relatively constant root concentration factors (RCFs) on the basis of pharmaceutical concentration in soil pore water, compared to the highly variable RCFs derived from soils, suggest that pore water-based RCF is superior for describing pharmaceutical accumulation in plants grown in soils. We recommend that pharmaceuticals in soil pore water should be evaluated and included in modeling their uptake by plants.
Subject(s)
Raphanus , Soil Pollutants , Pharmaceutical Preparations , Plants , Soil , Soil Pollutants/analysis , WaterABSTRACT
In the photonic design problem, a scientist or engineer chooses the physical parameters of a device to best match some desired device behavior. Many instances of the photonic design problem can be naturally stated as a mathematical optimization problem that is computationally difficult to solve globally. Because of this, several heuristic methods have been developed to approximately solve such problems. These methods often produce very good designs, and, in many practical applications, easily outperform 'traditional' designs that rely on human intuition. Yet, because these heuristic methods do not guarantee that the approximate solution found is globally optimal, the question remains of just how much better a designer might hope to do. This question is addressed by performance bounds or impossibility results, which determine a performance level that no design can achieve. We focus on algorithmic performance bounds, which involve substantial computation to determine. We illustrate a variety of both heuristic methods and performance bounds on two examples. In these examples (and many others not reported here) the performance bounds show that the heuristic designs are nearly optimal, and can be considered globally optimal in practice. This review serves to clearly set up the photonic design problem and unify existing approaches for calculating performance bounds, while also providing some natural generalizations and properties.
ABSTRACT
BACKGROUND: High-throughput omics technologies have enabled the comprehensive reconstructions of genome-scale metabolic networks for many organisms. However, only a subset of reactions is active in each cell which differs from tissue to tissue or from patient to patient. Reconstructing a subnetwork of the generic metabolic network from a provided set of context-specific active reactions is a demanding computational task. RESULTS: We propose SWIFTCC and SWIFTCORE as effective methods for flux consistency checking and the context-specific reconstruction of genome-scale metabolic networks which consistently outperform the previous approaches. CONCLUSIONS: We have derived an approximate greedy algorithm which efficiently scales to increasingly large metabolic networks. SWIFTCORE is freely available for non-commercial use in the GitHub repository at https://mtefagh.github.io/swiftcore/.
Subject(s)
Metabolic Networks and Pathways/genetics , Software , Algorithms , Genome , HumansABSTRACT
Flux coupling analysis (FCA) aims to describe the functional dependencies among reactions in a metabolic network. Currently studied coupling relations are qualitative in the sense that they identify pairs of reactions for which the activity of one reaction necessitates the activity of the other one, but without giving any numerical bounds relating the possible activity rates. The potential applications of FCA are heavily investigated, however apart from some trivial cases there is no clue of what bottleneck in the metabolic network causes each dependency. In this article, we introduce a quantitative approach to the same flux coupling problem named quantitative flux coupling analysis (QFCA). It generalizes the current concepts as we show that all the qualitative information provided by FCA is readily available in the quantitative flux coupling equations of QFCA, without the need for any additional analysis. Moreover, we design a simple algorithm to efficiently identify these flux coupling equations which scales up to the genome-scale metabolic networks with thousands of reactions and metabolites in an effective way. Furthermore, this framework enables us to quantify the "strength" of the flux coupling relations. We also provide different biologically meaningful interpretations, including one which gives an intuitive certificate of precisely which metabolites in the network enforce each flux coupling relation. Eventually, we conclude by suggesting the probable application of QFCA to the metabolic gap-filling problem, which we only begin to address here and is left for future research to further investigate.
Subject(s)
Metabolic Networks and Pathways , Models, Biological , Algorithms , Linear Models , Mathematical Concepts , Metabolic Networks and Pathways/genetics , Systems BiologyABSTRACT
The present review examines the relations between sleep disturbance and anxiety in children and adolescents. The review begins with a detailed discussion of normative developmental trends in sleep, and the relation between sleep quality and emotion dysregulation in children. The extant literature on sleep disturbance in clinically anxious children with a focus on subjective versus objective measures of sleep is then summarized in detail. Finally, a review of the reciprocal relationship between sleep and emotion regulation is provided. The available research suggests that sleep disturbance is quite prevalent in children with anxiety disorders, although the directionality of the association between sleep disturbance and anxiety in children remains unclear. Despite this limitation, a reciprocal relationship between sleep quality and anxiety appears to be well established. Research using objective measures of sleep quality (e.g. polysomnography, sleep actigraphy, sleep bruxism) is warranted to better understand this relation. Further, complicating factors such as the environment in which sleep quality is measured, the developmental stage of participants, varying severity of anxiety and the timeframe during which assessment takes place should all be considered when examining sleep disturbance in this population.
Subject(s)
Anxiety Disorders/psychology , Neurodevelopmental Disorders/psychology , Sleep Wake Disorders/psychology , Actigraphy/methods , Adolescent , Anxiety Disorders/diagnosis , Anxiety Disorders/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Male , Neurodevelopmental Disorders/diagnosis , Neurodevelopmental Disorders/epidemiology , Polysomnography/methods , Sleep/physiology , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/epidemiologyABSTRACT
ABSTRACTBackground:The atypical antipsychotics (AAPs) are associated with a recognized class effect of glucose and lipid dysregulation. The use of these medications is rapidly increasing in elderly patients with, and without, dementia. However, the metabolic risks specific to elderly remain poorly studied. METHODS: Design: A case-control study. SETTING: Psychogeriatric service in Auckland, New Zealand. PARTICIPANTS: Elderly patients either receiving AAP treatment (cases) or not (controls) between 1 Jan 2008 and 1 Jan 2014. MAIN OUTCOME MEASURES: metabolic data of glucose, HbA1c, lipids, and cardiovascular events and death. The data were analyzed using t-tests and linear regression models for each metabolic outcome. RESULTS: There were 330 eligible cases and 301 controls from a total study population of 5,307. There was a statistically significant change in the HbA1c over time, within the cases group of -1.14 mmol/mol (p = 0.018, 95% CI -0.19 to -2.09). Also statistically significant was the reduction in total cholesterol of -0.13 mmol/L (p = 0.036, 95% CI -0.008 to -0.245). The only significant difference found between cases and controls was in the change in cholesterol ratio of 0.16 mmol/L between groups (95%CI 0.01-0.31, p = 0.036). CONCLUSIONS: AAP use was not associated with any clinically significant change in metabolic outcomes in this study population.
Subject(s)
Antipsychotic Agents/adverse effects , Blood Glucose/analysis , Dementia/blood , Metabolic Diseases/chemically induced , Aged , Antipsychotic Agents/therapeutic use , Dementia/drug therapy , Dementia/psychology , Female , Humans , Lipids/blood , MaleABSTRACT
Increasing concentrations of anthropogenic antibiotics in soils are partly responsible for the proliferation of bacterial antibiotic resistance. However, little is known about how soil-sorbed antibiotics exert selective pressure on bacteria in unsaturated soils. This study investigated the bioavailability of tetracycline sorbed on three soils (Webster clay loam, Capac sandy clay loam, and Oshtemo loamy sand) to a fluorescent Escherichia coli bioreporter under unsaturated conditions using agar diffusion assay, microscopic visualization, and model simulation. Tetracycline sorbed on the soils could be desorbed and become bioavailable to the E. coli cells at matric water potentials of -2.95 to -13.75 kPa. Bright fluorescent rings were formed around the tetracycline-loaded soils on the unsaturated agar surfaces, likely due to radial diffusion of tetracycline desorbed from the soils, tetracycline uptake by the E. coli cells, and its inhibition on E. coli growth, which was supported by the model simulation. The bioavailability of soil-sorbed tetracycline was much higher for the Oshtemo soil, probably due to faster diffusion of tetracycline in coarse-textured soils. Decreased bioavailability of soil-sorbed tetracycline at lower soil water potential likely resulted from reduced tetracycline diffusion in soil pore water at smaller matric potential and/or suppressed tetracycline uptake by E. coli at lower osmotic potential. Therefore, soil-sorbed tetracycline could still exert selective pressure on the exposed bacteria, which was influenced by soil physical processes controlled by soil texture and soil water potential.
Subject(s)
Biological Availability , Escherichia coli , Soil Pollutants/pharmacokinetics , Tetracycline/pharmacokinetics , Anti-Bacterial Agents , SoilABSTRACT
Activated carbon (AC) is an increasingly attractive remediation alternative for the sequestration of dioxins at contaminated sites globally. However, the potential for AC to reduce the bioavailability of dioxins in mammals and the residing gut microbiota has received less attention. This question was partially answered in a recent study examining 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced hallmark toxic responses in mice administered with TCDD sequestered by AC or freely available in corn oil by oral gavage. Results from that study support the use of AC to significantly reduce the bioavailability of TCDD to the host. Herein, we examined the bioavailability of TCDD sequestered to AC on a key murine gut commensal and the influence of AC on the community structure of the gut microbiota. The analysis included qPCR to quantify the expression of segmented filamentous bacteria (SFB) in the mouse ileum, which has responded to TCDD-induced host toxicity in previous studies and community structure via sequencing the 16S ribosomal RNA (rRNA) gene. The expression of SFB 16S rRNA gene and functional genes significantly increased with TCDD administered with corn oil vehicle. Such a response was absent when TCDD was sequestered by AC. In addition, AC appeared to have a minimal influence on murine gut community structure and diversity, affecting only the relative abundance of Lactobacillaceae and two other groups. Results of this study further support the remedial use of AC for eliminating bioavailability of TCDD to host and subsequent influence on the gut microbiome.
Subject(s)
Charcoal/administration & dosage , Gastrointestinal Microbiome/drug effects , Polychlorinated Dibenzodioxins/administration & dosage , Animals , Biological Availability , Charcoal/pharmacokinetics , Corn Oil/administration & dosage , Corn Oil/pharmacokinetics , Female , Ileum/microbiology , Lactobacillaceae/metabolism , Mice , Polychlorinated Dibenzodioxins/pharmacokinetics , Polychlorinated Dibenzodioxins/toxicity , RNA, Ribosomal, 16S/genetics , TranscriptomeABSTRACT
BACKGROUND: A single-nucleotide polymorphism (SNP) in GABRA2 (rs279858) may moderate subjective response (SR) to alcohol. Results of studies in non-dependent drinkers examining this GABRA2 SNP on SR have been equivocal. This study examined this SNP's direct and indirect effects on alcohol self-administration in dependent drinkers. METHOD: The sample consisted of 63 Caucasian, non-treatment-seeking individuals with alcohol dependence. Subjective stimulation was assessed using the Biphasic Alcohol Effects Scale following consumption of an alcoholic priming drink (target breath alcohol content = 0.02 g%). Participants were subsequently offered the opportunity to self-administer up to eight additional drinks. RESULTS: Controlling for baseline stimulation, T-allele homozygotes, relative to individuals with at least one copy of the C-allele, reported greater initial stimulation, t(58) = 2.011, p = 0.049. Greater stimulation predicted greater subsequent alcohol self-administration, t(57) = 2.522, p = 0.015. Although rs279858 genotype did not directly impact self-administration (t(57) = -0.674, p = 0.503), it did have an indirect effect (95% confidence interval [0.068, 1.576]), such that T-allele homozygotes reported greater stimulation, which in turn predicted greater self-administration. CONCLUSION: These results suggest that the influence of this SNP on SR differs depending on dose or stage of dependence. This study is the first to demonstrate an indirect effect of rs279858 genotype on drinking through SR. Although C-allele carriers have been shown to have an increased risk for alcohol dependence, in our dependent sample, greater stimulation was found among T-allele homozygotes, suggesting that the influence of SR on developing and maintaining dependence differs based on rs279858 genotype.This study demonstrates an indirect effect of rs279858 genotype on drinking through SR. Although C-allele carriers have an increased risk for alcohol dependence, in our dependent sample, greater stimulation was found among T-allele homozygotes, suggesting that the influence of SR on developing dependence differs based on rs279858 genotype.
Subject(s)
Alcoholism/genetics , Ethanol/pharmacology , Polymorphism, Single Nucleotide , Receptors, GABA-A/genetics , Adult , Alcohol Drinking/genetics , Alcohol Drinking/physiopathology , Alcoholism/physiopathology , Alleles , Female , Homozygote , Humans , Male , Middle Aged , Receptors, GABA-A/physiology , Young AdultABSTRACT
The presence of antibiotics in agroecosystems raises concerns about the proliferation of antibiotic-resistant bacteria and adverse effects to human health. Soil amendment with biochars pyrolized from manures may be a win-win strategy for novel manure management and antibiotics abatement. In this study, lincomycin sorption by manure-derived biochars was examined using batch sorption experiments. Lincomycin sorption was characterized by two-stage kinetics with fast sorption reaching quasi-equilibrium in the first 2 d, followed by slow sorption over 180 d. The fast sorption was primarily attributed to surface adsorption, whereas the long-term slow sorption was controlled by slow diffusion of lincomycin into biochar pore structures. Two-day sorption experiments were performed to explore effects of biochar particle size, solid/water ratio, solution pH, and ionic strength. Lincomycin sorption to biochars was greater at solution pH 6.0 to 7.5 below the dissociation constant of lincomycin (7.6) than at pH 9.9 to 10.4 above its dissociation constant. The enhanced lincomycin sorption at lower pH likely resulted from electrostatic attraction between the positively charged lincomycin and the negatively charged biochar surfaces. This was corroborated by the observation that lincomycin sorption decreased with increasing ionic strength at lower pH (6.7) but remained constant at higher pH (10). The long-term lincomycin sequestration by biochars was largely due to pore diffusion plausibly independent of solution pH and ionic composition. Therefore, manure-derived biochars had lasting lincomycin sequestration capacity, implying that biochar soil amendment could significantly affect the distribution, transport, and bioavailability of lincomycin in agroecosystems.
Subject(s)
Charcoal , Lincomycin/chemistry , Manure , Adsorption , Soil , WaterABSTRACT
BACKGROUND AND OBJECTIVES: Percutaneous coronary intervention (PCI) in patients with lesions of large calibre coronary arteries (≥ 5 mm) and saphenous venous grafts (≥ 5 mm) can be challenging. There are no separate guidelines available to treat these vessels with PCI. Standard coronary stents of 4 mm diameter are used to treat these lesions conventionally but carry the risk of under deployment, distortion of stent architecture and future stent thrombosis even if they are subsequently expanded beyond 5 mm. METHODS AND RESULTS: Biliary stents (Herculink Elite™) provide a better alternative to standard coronary stents in these patients. These stents are of larger diameter (5-7 mm) and can be safely delivered over a 6 French sheath. In our case series, we demonstrate the use of intravascular ultrasound examination to confirm that biliary stents provide improved stent strut apposition within the coronary artery associated with extremely low repeat revascularisation rates. CONCLUSION: Our paper highlights that PCI of lesions in patients with large calibre coronary arteries can successfully be achieved using biliary stents.
Subject(s)
Coronary Stenosis/therapy , Prosthesis Implantation , Stents , Coronary Angiography , Coronary Stenosis/diagnostic imaging , Coronary Vessels/diagnostic imaging , Feasibility Studies , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention , Prosthesis Design , Retrospective Studies , Saphenous Vein/diagnostic imaging , Saphenous Vein/transplantation , Ultrasonography, InterventionalABSTRACT
Complexation of tetracycline with dissolved organic matter (DOM) in aqueous solution could alter the bioavailability of tetracycline to bacteria, thereby alleviating selective pressure for development of antibiotic resistance. In this study, an Escherichia coli whole-cell bioreporter construct with antibiotic resistance genes coupled to green fluorescence protein was exposed to tetracycline in the presence of DOM derived from humic acids. Complexation between tetracycline and DOM diminished tetracycline bioavailability to E. coli, as indicated by reduced expression of antibiotic resistance genes. Increasing DOM concentration resulted in decreasing bioavailability of tetracycline to the bioreporter. Freely dissolved tetracycline (not complexed with DOM) was identified as the major fraction responsible for the rate and magnitude of antibiotic resistance genes expressed. Furthermore, adsorption of DOM on bacterial cell surfaces inhibited tetracycline diffusion into the bioreporter cells. The magnitude of the inhibition was related to the amount of DOM adsorbed and tetracycline affinity for the DOM. These findings provide novel insights into the mechanisms by which the bioavailability of tetracycline antibiotics to bacteria is reduced by DOM present in water. Agricultural lands receiving livestock manures commonly have elevated levels of both DOM and antibiotics; the DOM could suppress the bioavailability of antibiotics, hence reducing selective pressure on bacteria for development of antibiotic resistance.
Subject(s)
Escherichia coli/drug effects , Tetracycline Resistance , Tetracycline/pharmacokinetics , Water Pollutants, Chemical/pharmacokinetics , Adsorption , Anti-Bacterial Agents/pharmacology , Biological Availability , Drug Resistance, Microbial/drug effects , Escherichia coli/genetics , Escherichia coli/metabolism , Humic Substances/analysis , Tetracycline/metabolism , Water/chemistry , Water Pollutants, Chemical/analysisABSTRACT
A new photoreduction pathway for nitro-aromatic compounds (NACs) and the underlying degradation mechanism are described. 1,3-Dinitrobenzene was reduced to 3-nitroaniline by the widely distributed aromatic molecule indole; the reaction is facilitated by montmorillonite clay mineral under both simulated and natural sunlight irradiation. The novel chemical reaction is strongly affected by the type of exchangeable cation present on montmorillonite. The photoreduction reaction is initiated by the adsorption of 1,3-dinitrobenzene and indole in clay interlayers. Under light irradiation, the excited indole molecule generates a hydrated electron and the indole radical cation. The structural negative charge of montmorillonite plausibly stabilizes the radical cation hence preventing charge recombination. This promotes the release of reactive hydrated electrons for further reductive reactions. Similar results were observed for the photoreduction of nitrobenzene. In situ irradiation time-resolved electron paramagnetic resonance and Fourier transform infrared spectroscopies provided direct evidence for the generation of hydrated electrons and the indole radical cations, which supported the proposed degradation mechanism. In the photoreduction process, the role of clay mineral is to both enhance the generation of hydrated electrons and to provide a constrained reaction environment in the galley regions, which increases the probability of contact between NACs and hydrated electrons.
Subject(s)
Bentonite/chemistry , Nitro Compounds/chemistry , Photochemical Processes , Adsorption , Aluminum Silicates , Aniline Compounds/chemistry , Cations/chemistry , Clay , Dinitrobenzenes/chemistry , Electron Spin Resonance Spectroscopy , Electrons , Indoles/chemistry , Light , Nitrobenzenes/chemistry , Spectroscopy, Fourier Transform InfraredABSTRACT
Strong sorption of planar nonionic organic chemicals by clay minerals has been observed for important classes of organic contaminants including polyaromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and dioxins, and such affinity was hypothesized to relate to the interlayer hydrophobicity of smectite clays. In batch sorption experiments of two trichlorobiphenyls on homoionic Na-, K-, Cs-montmorillonites, considerably greater sorption coefficient (Kw) was observed for coplanar 3,3',5-trichlorobiphenyl (PCB 36); log Kw for Na-, K-, and Cs-montmorillonite were 3.69, 3.72, and 4.53 for coplanar PCB 36 vs 1.21, 1.46, and 0.87 for the nonplanar 2,2',6-trichlorobiphenyl (PCB 19). MD simulations were conducted utilizing X-ray diffraction determined clay interlayer distances (d-spacing). The trajectory, density distribution, and radial distribution function of interlayer cation, water, and PCBs collectively indicated that the hydrophobic nature of the interlayer regions was determined by the hydration status of exchangeable cations and the associated d-spacing. The sorption free energies calculated for both coplanar and nonplanar PCB molecules by adaptive biasing force (ABF) method with an extended interlayer-micropore two-phase model consisting of cleaved clay hydrates and "bulk water" are consistent with the Gibbs free energies derived from the measured log Kw, manifesting enhanced sorption of coplanar PCBs was attributed to shape selectivity and hydrophobic interactions.
Subject(s)
Bentonite/chemistry , Polychlorinated Biphenyls/chemistry , Adsorption , Cations , ThermodynamicsABSTRACT
BACKGROUND: Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) frequently co-occur. Previous research demonstrates the utility of goals in attaining improved SUD outcomes, however, no previous studies have examined goal choices in the context of integrated treatment for comorbid PTSD and SUD. OBJECTIVES: The present study investigated correlates of treatment entry goals to either reduce or abstain from substance use. METHODS: Participants (N = 60) were treatment-seeking veterans with current PTSD and SUD. Participants completed self-report and clinician-rated measures of substance use, PTSD, and affective symptoms as part of a larger randomized controlled trial. RESULTS: Half (30/60) of participants endorsed a treatment entry goal to reduce substance use (reducers). Compared to participants who endorsed a treatment entry goal of abstinence (abstainers), reducers were significantly younger, more likely to be employed, more likely to have served in recent military conflicts (Operations Enduring/Iraqi Freedom), and endorsed significantly fewer symptoms of alcohol dependence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The findings demonstrate clinically relevant differences based on treatment entry goals, suggesting that individuals are often able to choose conceivably appropriate treatment goals based, most notably, on the severity of their SUD. Collaboratively engaging patients in establishing treatment goals that are consistent with their beliefs and desires in conjunction with empirical findings is particularly relevant in the context of treatment for SUD and PTSD where many patients are ambivalent about treatment and attrition is common.
Subject(s)
Goals , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/psychology , Substance-Related Disorders/epidemiology , Substance-Related Disorders/psychology , Veterans/psychology , Adolescent , Adult , Aged , Comorbidity , Female , Humans , Male , Middle Aged , South Carolina/epidemiology , Young AdultABSTRACT
Tetracycline contains ionizable functional groups that manifest several species with charges at different locales and differing net charge; the fractional distribution of each species depends on pH-pKa relationship in the aqueous phase. In nature, these species interact with naturally abundant cations (e.g., Ca(2+) and Mg(2+)) to form metal-tetracycline complexes in water. In this study, we used Escherichia coli MC4100/pTGM whole-cell bioreporter to investigate tetracycline uptake from solution under varying conditions of pH, salt composition and concentration by quantifying the corresponding expression of antibiotic resistance gene. The expression of antibiotic resistance gene in the E. coli bioreporter responded linearly to intracellular tetracycline concentration. Less tetracycline entered E. coli cells at solution pH of 8.0 than at pH 6.0 or 7.0 indicating reduced bioavailability of the antibiotic at higher pH. Both Mg(2+) and Ca(2+) in solution formed metal-tetracycline complexes which reduced uptake of tetracycline by E. coli hence diminishing the bioresponse. Among the various tetracycline species present in solution, including both metal-complexed and free (noncomplexed) species, zwitterionic tetracycline was identified as the predominant species that most readily passed through the cell membrane eliciting activation of the antibiotic resistance gene in E. coli. The results indicate that the same total concentration of tetracycline in ambient solution can evoke very different expression of antibiotic resistance gene in the exposed bacteria due to differential antibiotic uptake. Accordingly, geochemical factors such as pH and metal cations can modulate the selective pressure exerted by tetracycline for development and enrichment of antibiotic resistant bacteria. We suggest that tetracycline speciation analysis should be incorporated into the risk assessment framework for evaluating environmental exposure and the corresponding development of antibiotic resistance.
Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacokinetics , Drug Resistance, Microbial , Escherichia coli/metabolism , Tetracyclines/chemistry , Tetracyclines/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Biological Availability , Chromatography, Liquid , Escherichia coli/drug effects , Escherichia coli/genetics , Genes, Bacterial , Genes, Reporter , Hydrogen-Ion Concentration , Promoter Regions, Genetic , Tandem Mass Spectrometry , Tetracyclines/pharmacologyABSTRACT
Manganese(III) geocomponents are commonly found in the soil environment, yet their roles in many biogeochemical processes remain unknown. In this study, we demonstrated that Mn(III) generated from the reaction of MnO(2) and oxalic acid caused rapid and extensive decompositions of a quinoxaline-di-N-oxide antibiotics, viz carbadox. The reaction occurred primarily at the quinoxaline-di-N-oxide moiety resulting in the removal of one -O from N1-oxide and formation of desoxycarbadox. The reaction rate was accelerated by increasing amounts of Mn(III), carbadox and oxalate. The critical step in the overall reaction was the formation of a quinoxaline-di-N-oxide/Mn(III)/oxalate ternary complex in which Mn(III) functioned as the central complexing cation and electron conduit in which the arrangement of ligands facilitated electron transfer from oxalate to carbadox. In the complex, the C-C bond in oxalate was cleaved to create CO(2)(-â¢) radicals, followed by electron transfer to carbadox through the Mn(III) center. This proposed reaction mechanism is supported by the reaction products formed, reaction kinetics, and quantum mechanical calculations. The results obtained from this study suggest that naturally occurring Mn(III)-oxalic acid complexes could reductively decompose certain organic compounds in the environment such as the antibiotic quinoxaline-di-N-oxide.
Subject(s)
Carbadox/chemistry , Manganese/chemistry , Oxalic Acid/chemistry , Kinetics , Models, Chemical , Oxidation-Reduction , Quinoxalines/chemistry , Solutions , ThermodynamicsABSTRACT
Neuropsychologists can expect to meet with increasing rates of patients who use methamphetamine (MA), as MA use is on the rise, often comorbid with other substance use disorders, and frequently accompanied by changes in cognitive functioning. To detect impairment, neuropsychologists must apply the appropriate normative data according to important demographic factors such as age, sex, and education. This study involved 241 adults with and without MA dependence who were administered the Neuropsychological Assessment Battery. Given the high rates of polysubstance use among adults who use MA, we included adults with mono-dependence and poly-dependence on MA and at least one other substance. We compared the rates of adults with and without previous MA dependence classified as impaired on neurocognitive testing when using norms corrected for age, education, and sex versus norms corrected only for age. Norms corrected for age, education, and sex resulted in less frequent identification of impairment compared to norms corrected only for age, but both sets of norms appeared sufficient and similar enough to warrant their use with this population. It may be appropriate to explore the possible implications of discrepancies between education-corrected and non-education corrected sets of scores when assessing impairment in individuals who use MA.