Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.405
Filtrar
1.
Ecotoxicol Environ Saf ; 196: 110561, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32276163

RESUMO

A ternary catalysis system was investigated to evaluate the comparative degradation of toxic fungicide metabolite 3,5-dichloroaniline (3,5-DCA) by laccase and MnO2 with mediators. In this study, copper based fungal enzyme laccase (Trametes versicolor origin) and metal catalyst MnO2 with various combinations of phenolic mediators (catechol, syringaldehyde, syringic acid, caffeic acid and gallic acid) were monitored to optimize and screen the better one for 3,5-DCA degradation assay. Catechol showed better potentiality in reduction of 3,5-DCA among the studied mediators. Catechol (2mM) showed the highest reduction rate (99-100%) followed by syringaldehyde (40.51%) with 2U/mL of laccase at 25 °C within 24 h reaction time. Similarly, complete degradation of 3,5-DCA was obtained by catechol (2mM) with 2 mg/mL of MnO2 in MnO2-mediator assay. The notable finding of current study indicated the triggering of catechol for better 3,5-DCA degradation at higher pH condition but inertness in laccase-mediator assay due to laccase destabilization. The reaction pathways of optimized mediator-based catalysis for laccase and MnO2 were proposed. Finally, the optimized laccase-catechol based degradation was considered as a pioneer green catalysis approach to reduce the toxic metabolite 3,5-DCA concentrations in aqueous medium as compared to MnO2-catechol catalysis.


Assuntos
Compostos de Anilina/análise , Fungicidas Industriais/análise , Lacase/metabolismo , Compostos de Manganês/química , Óxidos/química , Trametes/enzimologia , Compostos de Anilina/metabolismo , Benzaldeídos/química , Catálise , Catecóis/química , Fungicidas Industriais/metabolismo , Fenóis/química
2.
Chemosphere ; 243: 125426, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995879

RESUMO

The rapid start-up of sequencing batch reactor (SBR) was studied by adding efficient aniline-degrading bacteria strain AD4 (Delftia sp.), and the reactor start-up completion took only 15 days. The loading rate of aniline was 0.7 g aniline (g VSS*d)-1, which has been completely removed. The NH4+-N produced in the degradation process of aniline was also converted, which made the concentration of NH4+-N in the effluent of the reactor was always lower than that in the influent. Nitrification and denitrification played some roles in forming a dynamic equilibrium state of the whole system. The variation of microbial community during the start-up of the reactor was analyzed by high-throughput sequencing. At the phylum level, Proteobacteria, Bacteroidetes and Actinobacteria have always accounted for a large proportion. They also serve as functional bacteria for both aniline degradation and nitrogen removal. The biggest percentage jump was Flavobacterium and Acidovorax. The amount of high efficiency aniline degradation bacterium AD4 in the reactor increased at first, followed by decreasing and finally stabilized, which played an important role in the degradation of aniline.


Assuntos
Compostos de Anilina/metabolismo , Bactérias/metabolismo , Biodegradação Ambiental , Reatores Biológicos/microbiologia , Esgotos/microbiologia , Desnitrificação , Microbiota , Nitrificação , Nitrogênio/metabolismo
3.
Ecotoxicol Environ Saf ; 189: 109995, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31785947

RESUMO

The use of p-chloroaniline (PCA) in various aspects leads to its existence and accumulation in the environment. Relevant researches showed that PCA was a prime toxic pollutant that had imposed a serious risk to public health and the environment. This paper investigated the toxicity effects of PCA on Platymonas subcordiformis (P. subcordiformis) and the biodegradation of PCA by the marine microalga. In the toxicity experiments, the EC50 of PCA on P. subcordiformis at 24 h, 48 h, 72 h and 96 h was 41.42, 24.04, 17.15 and 13.05 mg L-1, respectively. The pigment parameters including chlorophyll a, chlorophyll b, carotenoids, photosynthetic O2 release rate, respiration O2 consumption rate and the chlorophyll fluorescence parameters including Fv/Fm, ETR and qP decreased greatly while antioxidant enzyme activities (SOD, CAT) and the chlorophyll fluorescence parameter NPQ increased when P. subcordiformis exposed to PCA compared with the control group. Fv/Fm would be a suitable indicator for assessing the toxicity of PCA in marine environment based on the analysis of Pearson's correlation coefficient and Integrated Biomarker Response (IBR). The degradation assay in P. subcordiformis indicated that the green marine microalga had the ability to remove and degrade PCA, and the order of removal and degradation proportion of PCA was 2 mg L-1 > 5 mg L-1>10 mg L-1. The maximum removal and biodegradation percentage was 54% and 34%, respectively.


Assuntos
Compostos de Anilina/toxicidade , Clorófitas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Compostos de Anilina/metabolismo , Biodegradação Ambiental , Carotenoides/metabolismo , Clorofila/metabolismo , Clorofila A/metabolismo , Clorófitas/metabolismo , Oxigênio/metabolismo , Fotossíntese/efeitos dos fármacos , Poluentes Químicos da Água/metabolismo
4.
Chemosphere ; 242: 125102, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31669985

RESUMO

Exposure history and adaptation of the inoculum to chemicals have been shown to influence the outcome of ready biodegradability tests. However, there is a lack of information about the mechanisms involved in microbial adaptation and the implication thereof for the tests. In the present study, we investigated the impact of a long-term exposure to N-methylpiperazine (NMP) and 4-chloroaniline (4CA) of an activated sludge microbial community using chemostat systems. The objective was to characterize the influence of adaptation to the chemicals on an enhanced biodegradation testing, following the OECD 310 guideline. Cultures were used to inoculate the enhanced biodegradability tests, in batch, before and after exposure to each chemical independently in chemostat culture. Composition and diversity of the microbial communities were characterised by 16s rRNA gene amplicon sequencing. Using freshly sampled activated sludge, NMP was not degraded within the 28 d frame of the test while 4CA was completely eliminated. However, after one month of exposure, the community exposed to NMP was adapted and could completely degrade it. This result was in complete contrast with that from the culture exposed for 3 months to 4CA. Long term incubation in the chemostat system led to a progressive loss of the initial biodegradation capacity of the community, as a consequence of the loss of key degrading microorganisms. This study highlights the potential of chemostat systems to induce adaptation to a specific chemical, ultimately resulting in its biodegradation. At the same time, one should be critical of these observations as the dynamics of a microbial community are difficult to maintain in chemostat, as the loss of 4CA biodegradation capacity demonstrates.


Assuntos
Compostos de Anilina/metabolismo , Biodegradação Ambiental , Microbiota/efeitos dos fármacos , Piperazina/metabolismo , Esgotos/microbiologia , RNA Ribossômico 16S , Fatores de Tempo
5.
Chemosphere ; 243: 125270, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31726261

RESUMO

Pendimethalin (PND) is a widely used herbicide in modern means of agricultural practices. So, its toxic residues exist extensively in the environment and can enter human body. Therefore, the in vitro interaction of PND with human serum albumin (HSA) has been explored by employing various biophysical, molecular docking and dynamics simulation studies as well as enzyme kinetics to unravel its binding mechanism. The binding constant of the PND-HSA complex was about 104 M-1 using Fluorescence quenching spectra. The negative value of Gibbs free energy change (ΔG0 = -32.0 kJ mol-1) indicates this interaction is a spontaneous process. A large negative ΔH0 and positive ΔS0 suggests that hydrophobic interactions and H-bonding are involved in the binding process of PND with HSA. The binding of PND can cause conformational and micro-environmental changes in HSA molecule, as shown by various biophysical and molecular dynamics simulation studies. The site marker competition and molecular docking and simulation experiments affirmed that the binding of PND to HSA occurs at or near site I. Esterase-like activity of HSA exhibited decline in the presence of PND revealed the direct involvement of Lys199 of subdomain IIA (Sudlow's site I) in the binding process.


Assuntos
Compostos de Anilina/química , Albumina Sérica Humana/química , Compostos de Anilina/metabolismo , Sítios de Ligação , Dicroísmo Circular , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Espectrometria de Fluorescência , Termodinâmica
6.
Artigo em Inglês | MEDLINE | ID: mdl-31707907

RESUMO

Among three monofluoroanilines, 2-fluoroaniline (2-FA) and 3-fluoroaniline (3-FA) exhibit relatively poor biodegradability. This work examined their degradation characteristics in a mixed culture system and also analyzed the microorganism community. After acclimation for 58 d and 43 d, the high removal efficiency of 100% of 2-FA and 95.3% of 3-FA was obtained by adding 25 mg L-1 of 2-FA or 3-FA to the two reactors, respectively. In addition, the high defluorination rates of 2-FA and 3-FA were observed to be 87.0% and 89.3%, respectively. The degradation kinetics showed that the maximum specific degradation rates of 2-FA and 3-FA were (21.23 ± 0.91) mg FA (g•VSS·h)-1, and (11.75 ± 0.99) mg FA (g•VSS·h)-1, respectively. PCR-DGGE analysis revealed that the unique bacteria degrading 2-FA were mainly composed of six genera (Novosphingobium, Bradyrhizobium, Aquaspirillum, Aminobacter, Ochrobactrum, and Labrys), and five genera that degraded 3-FA (Ochrobactrum, Aquaspirillum, Lachnobacterium, Bradyrhizobium, and Variovorax). Analysis of the key catabolic enzyme activities indicated that the simultaneous hydroxylation and dehalogenation were involved in monooxygenase elimination of 2-FA and conversion of 3-FA to 4-fluorocatechol by dioxygenase, indicating that enriched mixed cultures were effective to metabolize 2-FA or 3-FA by unconventional pathways to prevent the accumulation of toxic metabolites.


Assuntos
Compostos de Anilina/metabolismo , Fluorbenzenos/metabolismo , Microbiota , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biodegradação Ambiental , Reatores Biológicos/microbiologia , Halogenação , Hidroxilação , Cinética , Microbiota/genética
7.
J Pharm Biomed Anal ; 177: 112871, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31539712

RESUMO

Osimertinib is a "third-generation'' oral, irreversible, tyrosine kinase inhibitor. It is used in the treatment of non-small cellular lung carcinoma and spares wild-type EGFR. Due to its reactive nature, osimertinib is, in addition to oxidative routes, metabolized through GSH coupling and subsequent further metabolism of these conjugates. The extent of the non-oxidative metabolism of osimertinib is unknown, and methods to quantify this metabolic route have not been reported yet. To gain insight into this metabolic route, a sensitive bioanalytical assay was developed for osimertinib, the active desmethyl metabolite AZ5104, and the thio-metabolites osimertinibs glutathione, cysteinylglycine, and cysteine conjugates was developed. The ease of synthesis of these metabolites was a key-part in the development of this assay. This was done through simple one-step synthesis and subsequent LC-purification. The compounds were characterized by NMR and high-resolution mass spectrometry. Sample preparation was done by a simple protein crash with acetonitrile containing the stable isotopically labeled internal standards for osimertinib and the thio-metabolites, partial evaporation of solvents, and reconstitution in eluent, followed by UHPLC-MS/MS quantification. The assay was successfully validated in a 2-2000 nM calibration range for all compounds except the glutathione metabolite, where the LLOQ was set at 6 nM due to low accuracy at 2 nM. Limited stability was observed for osimertinib, AZ5104, and the glutathione metabolite. The clinical applicability of the assay was demonstrated in samples of patients treated with 80 mg osimertinib once daily, containing all investigated compounds at detectable and quantifiable levels.


Assuntos
Acrilamidas/farmacocinética , Compostos de Anilina/farmacocinética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacocinética , Acrilamidas/administração & dosagem , Acrilamidas/sangue , Acrilamidas/metabolismo , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/administração & dosagem , Compostos de Anilina/sangue , Compostos de Anilina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/genética , Cromatografia Líquida de Alta Pressão/métodos , Dipeptídeos/sangue , Dipeptídeos/síntese química , Dipeptídeos/metabolismo , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Glutationa/sangue , Glutationa/síntese química , Glutationa/metabolismo , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/genética , Pessoa de Meia-Idade , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/sangue , Inibidores de Proteínas Quinases/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/síntese química , Compostos de Sulfidrila/metabolismo , Espectrometria de Massas em Tandem/métodos
8.
Chemosphere ; 240: 124945, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31726594

RESUMO

In this study, the effect of high concentration of Mn2+ on the aerobic granular sludge (AGS) systems for aniline wastewater treatment was systematically investigated in terms of AGS formation and pollutant removal efficiency. Two parallel sequencing batch reactors were operated to treat the aniline-rich wastewater with and without 20 mg L-1 of Mn2+. In the presence of Mn2+, the time to granulation was prolonged from 23 d to 30 d due to the toxicity of the high concentration of Mn2+. However, the mature granules with Mn2+ produced more protein and polysaccharides, and had a larger size (870 µm) than that without Mn2+ (740 µm). The extracellular polymeric substances of the granules in the two reactors had similar protein compositions, but some functional groups increased with Mn2+. The reactors showed high overall removal efficiency of chemical oxygen demand, NH4+-N, and total nitrogen with average concentrations below 40, 1.0, and 19 mg L-1, respectively, in the effluents. In one typical operating cycle, however, Mn2+ retarded nitrification and the degradation of aniline, while promoted denitrification. The microbial community analysis revealed that the growth of Terrisporobacter, Pseudomonas, and many other bacteria responsible for aniline degradation was inhibited by Mn2+, and so were the strains involved in nitrification. In contrast, Mn2+ facilitated the growth of denitrifying bacteria.


Assuntos
Compostos de Anilina/toxicidade , Manganês/toxicidade , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/toxicidade , Aerobiose , Compostos de Anilina/metabolismo , Bactérias/metabolismo , Análise da Demanda Biológica de Oxigênio , Reatores Biológicos/microbiologia , Desnitrificação , Microbiota , Nitrificação , Nitrogênio/análise , Esgotos/química , Águas Residuárias/química
9.
Chemosphere ; 238: 124571, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472351

RESUMO

Rhodococcus exhibits strong adaptability to environmental stressors and plays a crucial role in environmental bioremediation. However, seasonal changes in ambient temperature, especially rapid temperature drops exert an adverse effect on in situ bioremediation. In this paper, we studied the cell morphology and fatty acid composition of an aniline-degrading strain Rhodococcus sp. CNS16 at temperatures of 30 °C, 20 °C, and 10 °C. At suboptimal temperatures, cell morphology of CNS16 changed from short rod-shaped to long rod or irregular shaped, and the proportion of unsaturated fatty acids was upregulated. Transcriptomic technologies were then utilized to gain detailed insights into the adaptive mechanisms of CNS16 subjected to suboptimal temperatures. The results showed that the number of gene responses was significantly higher at 10 °C than that at 20 °C. The inhibition of peptidoglycan synthase expression and up-regulation of Filamentous Temperature Sensitive as well as unsaturated fatty acid synthesis genes at suboptimal temperatures might be closely related to corresponding changes in cell morphology and fatty acids composition. Strain CNS16 showed loss of catalase and superoxide dismutase activity, and utilized thioredoxin-dependent thiol peroxidase to resist oxidative stress. The up-regulation of carotenoid and Vitamin B2 synthesis at 10 °C might also be involved in the resistance to oxidative stress. Amino acid metabolism, coenzyme and vitamin metabolism, ABC transport, and energy metabolism are essential for peptidoglycan synthesis and regulation of cellular metabolism; therefore, synergistically resisting environmental stress. This study provides a mechanistic basis for the regulation of aniline degradation in Rhodococcus sp. CNS16 at low temperatures.


Assuntos
Aclimatação/fisiologia , Compostos de Anilina/metabolismo , Ácidos Graxos/metabolismo , Peptidoglicano/biossíntese , Rhodococcus/metabolismo , Biodegradação Ambiental , Catalase/metabolismo , Temperatura Baixa , Estresse Oxidativo/fisiologia , Proteínas de Ligação às Penicilinas/biossíntese , Peroxirredoxinas/metabolismo , Rhodococcus/genética , Estações do Ano , Superóxido Dismutase/metabolismo , Transcriptoma
10.
J Agric Food Chem ; 67(46): 12816-12823, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31675231

RESUMO

Microbial degradation plays a major role in the dissipation of pendimethalin, and nitroreduction is an initial and detoxicating step. Previously, a pendimethalin nitroreductase, PNR, was identified in Bacillus subtilis Y3. Here, another pendimethalin nitroreductase from strain Y3, LNR, was identified. LNR shares only 40% identity with PNR and reduces the aromatic ring C-6 nitro group of pendimethalin and both nitro groups of trifluralin, butralin, and oryzalin. The catalytic activities against the four dinitroanilines were much higher for LNR than for PNR. lnr deletion significantly reduced the pendimethalin-reduction activity (60% activity loss), while pnr deletion led to only 30% activity loss, indicating that both LNR and PNR were involved in pendimethalin nitroreduction in strain Y3; however, LNR played the major role. This study facilitates the elucidation of pendimethalin catabolism and provides degrading enzyme resources for the removal of dinitroaniline herbicide residues in environment and agricultural products.


Assuntos
Compostos de Anilina/metabolismo , Bacillus subtilis/enzimologia , Proteínas de Bactérias/metabolismo , Herbicidas/metabolismo , Nitrorredutases/metabolismo , Sequência de Aminoácidos , Compostos de Anilina/química , Bacillus subtilis/classificação , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Biodegradação Ambiental , Herbicidas/química , Nitrorredutases/química , Nitrorredutases/genética , Filogenia , Alinhamento de Sequência
11.
Chem Commun (Camb) ; 55(87): 13152-13155, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31617527

RESUMO

We designed a supported lipid bilayer (SLB) biomimetic membrane system that comprised polyaniline (PANI) to support a lipid bilayer membrane that incorporated Na+/H+ transporter proteins (NhaA) to give the system the capability of controllable electrogenic ion transport. The high turnover rate of NhaA (∼105 per min) provides the basis for this PANI-SLB-NhaA system to be a high-speed rechargeable biocapacitor that functions as a low-energy-consuming fast switch for biological engineering applications.


Assuntos
Compostos de Anilina/metabolismo , Materiais Biomiméticos/metabolismo , Técnicas Biossensoriais , Proteínas de Escherichia coli/metabolismo , Bicamadas Lipídicas/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Compostos de Anilina/química , Materiais Biomiméticos/química , Espectroscopia Dielétrica , Eletrodos , Proteínas de Escherichia coli/química , Ouro/química , Ouro/metabolismo , Bicamadas Lipídicas/química , Trocadores de Sódio-Hidrogênio/química
12.
Ann Nucl Med ; 33(11): 848-854, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31456012

RESUMO

OBJECTIVE: Many studies have demonstrated the superiority of white matter (WM) reference regions (RR) in amyloid PET studies in comparison to cerebellar RR. However, the principle behind its improved measurement stability is yet to be elucidated. Our study aimed to determine the origin of WM stability; stability over cerebral blood flow and input function fluctuation or the greater statistical noise in the cerebellum due to its smaller size and its location in the axial periphery of the PET scanner bore. METHODS: We conducted simulations of [[Formula: see text]F] florbetapir using in-house program varying [Formula: see text] and input function, and adding statistical noise. RESULTS: Our simulations revealed that WM RR were more susceptible to CBF variation and input function fluctuation than cerebellar RR. WM RR did not gave superior measurement stability unless cerebellar statistical noise exceeded 4.55 times that in WM, a figure often surpassed in traditional amyloid PET studies. The greater statistical noise in cerebellum is likely the etiology for improved measurement stability of WM RR. CONCLUSION: A longitudinal [[Formula: see text]F] florbetapir PET study should be conducted with a long bore PET. It can also be hypothesized that a second scan with the cerebellum in the axial center of a 3D PET, using a cerebellar RR to calculate changes in tracer concentration may improve the measurement stability of longitudinal [[Formula: see text]F] florbetapir studies.


Assuntos
Compostos de Anilina/metabolismo , Etilenoglicóis/metabolismo , Modelos Biológicos , Tomografia por Emissão de Pósitrons , Substância Branca/diagnóstico por imagem , Substância Branca/metabolismo , Cinética , Razão Sinal-Ruído
13.
J Agric Food Chem ; 67(32): 9002-9008, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31322885

RESUMO

The diphenylurea 4,4'-dinitrocarbanilide (DNC) is the residue of concern left in edible tissues of broilers fed diets containing the anticoccidial nicarbazin. When chicken meat is submitted to thermal processing, p-nitroaniline (p-NA) is expected from DNC degradation. This work aimed at evaluating whether thermal processing of DNC-containing chicken meat induces p-NA appearance. First, a hydrolysis assay was performed in aqueous solutions at 100 °C in different pH, confirming that DNC cleavage yields p-NA. Then a novel LC-MS/MS method was used to detect traces of this aromatic amine in DNC-containing chicken breast fillets subjected to cooking methods. Our evidence showed p-NA occurrence in such chicken meat samples, which corroborated results from hydrolysis assay. The p-NA appearance in fillets was rather discrete during boiling treatment, but its concentration became pronounced over time for grilling, frying, and roasting, achieving respectively 326.3, 640.0, and 456.9 µg/kg. As far as we are concerned, no other research identified degradation products from DNC residue in heat-processed chicken fillets. Therefore, this study leads to additional approaches to assess impacts on food safety.


Assuntos
Compostos de Anilina/química , Carbanilidas/química , Coccidiostáticos/química , Resíduos de Drogas/química , Carne/análise , Nicarbazina/química , Compostos de Anilina/metabolismo , Animais , Carbanilidas/metabolismo , Galinhas/metabolismo , Coccidiostáticos/metabolismo , Culinária , Resíduos de Drogas/metabolismo , Temperatura Alta , Nicarbazina/metabolismo , Espectrometria de Massas em Tandem
14.
Syst Appl Microbiol ; 42(5): 125998, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345671

RESUMO

Desulfatiglans anilini is a sulfate-reducing bacterium (SRB) capable of oxidizing aniline, although growth and aniline turnover rates are slow, making it difficult to analyze the metabolism of the strain. Therefore, this study was designed to investigate the effect of sulfide on growth of D. anilini cultures, in order to improve its growth and aniline turnover rates, and study the biochemical mechanisms of sulfide inhibition. Hydrogen sulfide was found to inhibit growth of D. anilini, regardless of whether the strain was grown with aniline or phenol, and complete inhibition was observed at 20mM hydrogen sulfide. For improving the growth of D. anilini with aniline, the sulfide-consuming phototrophic bacterium Thiocapsa roseopersicina was co-cultured in a synthetic microbial community with D. anilini using a co-cultivation device that continuously removed hydrogen sulfide from the culture. The doubling time of D. anilini with aniline was 15 days in the co-cultivation device, compared to 26 days in the absence of a sulfide-oxidizing partner. Moreover, the aniline degradation rate was significantly increased by a factor of 2.66 during co-cultivation of D. anilini with T. roseopersicina. The initial carboxylation reaction during aniline degradation was measured in cell-free extracts of D. anilini with carbon dioxide (CO2) as a co-substrate in the presence of aniline and ATP. The effects of hydrogen sulfide on this aniline carboxylating system and on phenylphosphate synthase activity for phenol activation were studied, and it was concluded that hydrogen sulfide severely inhibited these enzyme activities.


Assuntos
Compostos de Anilina/metabolismo , Deltaproteobacteria/metabolismo , Microbiota , Thiocapsa roseopersicina/metabolismo , Biodegradação Ambiental , Técnicas de Cocultura , Deltaproteobacteria/efeitos dos fármacos , Deltaproteobacteria/crescimento & desenvolvimento , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Oxirredução , Fenóis/metabolismo
15.
Ann Neurol ; 86(4): 616-625, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31361916

RESUMO

OBJECTIVE: To determine whether amyloid imaging with the positron emission tomography (PET) agent Pittsburgh compound B (PiB) can detect vascular ß-amyloid (Aß) in the essentially pure form of cerebral amyloid angiopathy associated with the Dutch-type hereditary cerebral amyloid angiopathy (D-CAA) mutation. METHODS: PiB retention in a cortical composite of frontal, lateral, and retrosplenial regions (FLR) was measured by PiB-PET in 19 D-CAA mutation carriers (M+ ; 13 without neurologic symptoms, 6 with prior lobar intracerebral hemorrhage) and 17 mutation noncarriers (M- ). Progression of PiB retention was analyzed in a subset of 18 serially imaged individuals (10 asymptomatic M+ , 8 M- ). We also analyzed associations between PiB retention and cerebrospinal fluid (CSF) Aß concentrations in 17 M+ and 11 M- participants who underwent lumbar puncture and compared the findings to PiB-PET and CSF Aß in 37 autosomal dominant Alzheimer disease (ADAD) mutation carriers. RESULTS: D-CAA M+ showed greater age-dependent FLR PiB retention (p < 0.001) than M- , and serially imaged asymptomatic M+ demonstrated greater longitudinal increases (p = 0.004). Among M+ , greater FLR PiB retention associated with reduced CSF concentrations of Aß40 (r = -0.55, p = 0.021) but not Aß42 (r = 0.01, p = 0.991). Despite comparably low CSF Aß40 and Aß42, PiB retention was substantially less in D-CAA than ADAD (p < 0.001). INTERPRETATION: Increased PiB retention in D-CAA and correlation with reduced CSF Aß40 suggest this compound labels vascular amyloid, although to a lesser degree than amyloid deposits in ADAD. Progression in PiB signal over time suggests amyloid PET as a potential biomarker in trials of candidate agents for this untreatable cause of hemorrhagic stroke. ANN NEUROL 2019;86:616-625.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Angiopatia Amiloide Cerebral Familiar/diagnóstico por imagem , Heterozigoto , Adulto , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Compostos de Anilina/metabolismo , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos de Casos e Controles , Angiopatia Amiloide Cerebral Familiar/líquido cefalorraquidiano , Angiopatia Amiloide Cerebral Familiar/genética , Feminino , Neuroimagem Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem , Tomografia por Emissão de Pósitrons , Tiazóis/metabolismo
16.
Neurobiol Aging ; 81: 1-8, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207465

RESUMO

Individuals with autosomal dominant Alzheimer's disease (ADAD) present amyloid deposits before symptoms onset. We aimed to investigate efficacy and safety of 18F-florbetaben (FBB) for assessing amyloid deposition in ADAD. We acquired FBB positron emission tomography and magnetic resonance imaging of 25 individuals from PSEN1 families (NCT02362880). We studied individual uptake patterns, group differences, and correlation with estimated years to symptoms onset, as well as adverse events. We found that asymptomatic carriers (N = 14) showed increased FBB uptake across the cerebral cortex and in the caudate. FBB accumulation appeared more than 15 years before onset in the precuneus and bankssts, among other regions, overlapping regions showing increased cortical thickness in the same subjects. FBB uptake correlated with estimated years to symptoms onset in several areas, especially the rostral anterior cingulate. Symptomatic carriers (N = 7) had an elevated FBB uptake plateau. No adverse events were reported. Overall, we found progressive FBB uptake in ADAD starting 2 decades before symptoms. The rostral anterior cingulate is a candidate area to track Aß deposition in addition to the precuneus.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina/metabolismo , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/metabolismo , Radioisótopos de Flúor/metabolismo , Heterozigoto , Imagem por Ressonância Magnética , Mutação , Tomografia por Emissão de Pósitrons , Presenilinas/genética , Compostos Radiofarmacêuticos/metabolismo , Estilbenos/metabolismo , Adulto , Doença de Alzheimer/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Neurobiol Aging ; 81: 22-29, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31207466

RESUMO

We evaluated the associations of subjective (self-reported everyday cognition [ECog]) and objective cognitive measures with regional amyloid-ß (Aß) and tau accumulation in 86 clinically normal elderly subjects from the Alzheimer's Disease Neuroimaging Initiative. Regression analyses were conducted to identify whether individual ECog domains (Memory, Language, Organization, Planning, Visuospatial, and Divided Attention) were equally or differentially associated with regional [18F]florbetapir and [18F]flortaucipir uptake and how these associations compared to those obtained with objective cognitive measures. A texture analysis, the weighted 2-point correlation, was used as an additional approach for estimating the whole-brain tau burden without positron emission tomography intensity normalization. Although the strongest models for ECog domains included either tau (planning and visuospatial) or Aß (memory and organization), the strongest models for all objective measures included Aß. In Aß-negative participants, the strongest models for all ECog domains of executive functioning included tau. Our results indicate differential associations of individual subjective cognitive domains with Aß and tau in clinically normal adults. Detailed characterization of ECog may render a valuable prescreening tool for pathological prediction.


Assuntos
Envelhecimento , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina/metabolismo , Cognição , Disfunção Cognitiva , Etilenoglicóis/metabolismo , Radioisótopos de Flúor/metabolismo , Humanos , Neuroimagem , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/metabolismo
18.
Brain ; 142(7): 2096-2112, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31211359

RESUMO

Early biomarkers are needed to identify individuals at high risk of preclinical Alzheimer's disease and to better understand the pathophysiological processes of disease progression. Preclinical Alzheimer's disease EEG changes would be non-invasive and cheap screening tools and could also help to predict future progression to clinical Alzheimer's disease. However, the impact of amyloid-ß deposition and neurodegeneration on EEG biomarkers needs to be elucidated. We included participants from the INSIGHT-preAD cohort, which is an ongoing single-centre multimodal observational study that was designed to identify risk factors and markers of progression to clinical Alzheimer's disease in 318 cognitively normal individuals aged 70-85 years with a subjective memory complaint. We divided the subjects into four groups, according to their amyloid status (based on 18F-florbetapir PET) and neurodegeneration status (evidenced by 18F-fluorodeoxyglucose PET brain metabolism in Alzheimer's disease signature regions). The first group was amyloid-positive and neurodegeneration-positive, which corresponds to stage 2 of preclinical Alzheimer's disease. The second group was amyloid-positive and neurodegeneration-negative, which corresponds to stage 1 of preclinical Alzheimer's disease. The third group was amyloid-negative and neurodegeneration-positive, which corresponds to 'suspected non-Alzheimer's pathophysiology'. The last group was the control group, defined by amyloid-negative and neurodegeneration-negative subjects. We analysed 314 baseline 256-channel high-density eyes closed 1-min resting state EEG recordings. EEG biomarkers included spectral measures, algorithmic complexity and functional connectivity assessed with a novel information-theoretic measure, weighted symbolic mutual information. The most prominent effects of neurodegeneration on EEG metrics were localized in frontocentral regions with an increase in high frequency oscillations (higher beta and gamma power) and a decrease in low frequency oscillations (lower delta power), higher spectral entropy, higher complexity and increased functional connectivity measured by weighted symbolic mutual information in theta band. Neurodegeneration was associated with a widespread increase of median spectral frequency. We found a non-linear relationship between amyloid burden and EEG metrics in neurodegeneration-positive subjects, either following a U-shape curve for delta power or an inverted U-shape curve for the other metrics, meaning that EEG patterns are modulated differently depending on the degree of amyloid burden. This finding suggests initial compensatory mechanisms that are overwhelmed for the highest amyloid load. Together, these results indicate that EEG metrics are useful biomarkers for the preclinical stage of Alzheimer's disease.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/fisiopatologia , Eletroencefalografia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/classificação , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina/metabolismo , Biomarcadores/metabolismo , Ondas Encefálicas/fisiologia , Estudos de Casos e Controles , Progressão da Doença , Etilenoglicóis/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Degeneração Neural/patologia , Tomografia por Emissão de Pósitrons , Sintomas Prodrômicos
19.
Pharmacol Res ; 146: 104297, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31175939

RESUMO

Osimertinib is an irreversible EGFR inhibitor registered for advanced NSCLC patients whose tumors harbor recurrent somatic activating mutations in EGFR (EGFRm+) or the frequently occurring EGFR-T790M resistance mutation. Using in vitro transport assays and appropriate knockout and transgenic mouse models, we investigated whether the multidrug efflux transporters ABCB1 and ABCG2 transport osimertinib and whether they influence the oral availability and brain accumulation of osimertinib and its most active metabolite, AZ5104. In vitro, human ABCB1 and mouse Abcg2 modestly transported osimertinib. In mice, Abcb1a/1b, with a minor contribution of Abcg2, markedly limited the brain accumulation of osimertinib and AZ5104. However, no effect of the ABC transporters was seen on osimertinib oral availability. In spite of up to 6-fold higher brain accumulation, we observed no acute toxicity signs of oral osimertinib in Abcb1a/1b;Abcg2 knockout mice. Interestingly, even in wild-type mice the intrinsic brain penetration of osimertinib was already relatively high, which may help to explain the documented partial efficacy of this drug against brain metastases. No substantial effects of mouse Cyp3a knockout or transgenic human CYP3A4 overexpression on oral osimertinib pharmacokinetics were observed, presumably due to a dominant role of mouse Cyp2d enzymes in osimertinib metabolism. Our results suggest that pharmacological inhibition of ABCB1 and ABCG2 during osimertinib therapy might potentially be considered to further benefit patients with brain (micro-)metastases positioned behind an intact blood-brain barrier, or with substantial expression of these transporters in the tumor cells, without invoking a high toxicity risk.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Acrilamidas/metabolismo , Compostos de Anilina/metabolismo , Encéfalo/metabolismo , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Linhagem Celular , Citocromo P-450 CYP3A/metabolismo , Cães , Humanos , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Distribuição Tecidual/fisiologia
20.
Appl Microbiol Biotechnol ; 103(15): 6333-6344, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31119351

RESUMO

The residues of aniline and its derivatives are serious environment pollutants. Aniline dioxygenase (AD) derived from aerobic bacteria catalyzes the conversion of aniline to catechol, which has potential use in the bioremediation of aromatic amines and biorefining process. AD contains four components: a glutamine synthetase (GS)-like enzyme, a glutamine amidotransferase (GAT)-like enzyme, oxygenase, and reductase. ADs from diverse hosts exhibit different substrate specificities against aniline derivatives. However, what component of AD determines AD's substrate specificity is still unknown which limits the effects of extending AD's substrate spectrum through mutagenesis. Here, each component of two ADs (AtdA1A2A3A4A5 and AdoQTA1A2B) which have different substrate ranges was heterologously expressed and purified. The activity of both ADs was successfully constructed in vitro using the purified components. To identify the component that affects the substrate specificity of the ADs, the substrate specificity of each component was studied. The inability of AtdA1A2A3A4A5 to catalyze 4-methylaniline was determined with GS-like enzyme AtdA1; its inability to convert 2-isopropylaniline was caused by the oxygenase component, and its inability to convert 4-isopropylaniline was caused by both GS-like enzyme AtdA1 and oxygenase components. The inability of AdoQTA1A2B to catalyze 2-methylaniline was determined by GS-like enzyme AdoQ; its inability to convert 2-isopropylaniline was caused by both GS-like enzyme AdoQ and oxygenase components. Together, these results show that GS-like enzyme and oxygenase but not GAT-like enzyme or reductase play dominant roles in the substrate specificity of AD, and this finding will facilitate the engineering of AD to expand its substrate range.


Assuntos
Compostos de Anilina/metabolismo , Dioxigenases/metabolismo , Glutamato-Amônia Ligase/metabolismo , Complexos Multienzimáticos/metabolismo , Dioxigenases/química , Poluentes Ambientais/metabolismo , Glutamato-Amônia Ligase/química , Complexos Multienzimáticos/química , Especificidade por Substrato , Transaminases/química , Transaminases/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA