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1.
Sci Total Environ ; 813: 152282, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34902398

RESUMO

Concurrence of pharmaceuticals and personal care products (PPCPs), pathogenic viruses, metals and microbial pollution along with their seasonal variations in the water environment are overarching in the context of existing pandemic, especially for tropical countries. The present study focuses on the seasonal influence on the vulnerability of urban water in Guwahati, the largest city in North-eastern India, through examining the concurrence of seven PPCPs, five viruses, faecal bacteria and nine metals in surface waters during monsoon (Summer-July 2017) and pre-monsoon (Winter-March 2018). Surface water sampling was carried out at different locations of the Brahmaputra River, its tributary Bharalu River (an unlined urban drain), and Dipor Bill Lake (Ramsar-recognized wetland). Both PPCPs and viruses were at high concentrations (e.g. up to 970 ng L-1 caffeine, 2.5 × 103 copies mL-1 pepper mild mottle virus (PMMoV)) at the confluence points of urban drains and the river, while they were mostly undetectable at both upstream and downstream locations, implying strong self-purification ability of the river. All the analysed PPCPs and viruses were at much higher concentrations during pre-monsoon i.e., winter than during monsoon, implying heavy dilution and temperature effect during the monsoon. Overall, PPCPs and viruses were more correlated in monsoon but the risk quotient in the urban tributary was higher in pre-monsoon (e.g. 5061 in pre-monsoon and 1515 in monsoon for caffeine). PMMoV was found to be an excellent faecal pollution indicator due to its prevalence, detectability and specificity in all seasons. Overall, the seasonal fluctuations of the non-enveloped viruses monitored in this study is likely to be relevant for SARS-CoV-2. We contribute to address the literature scarcity pertaining to seasonal variations in the prevalence of viruses and their concurrences with contaminants of emerging concern.

2.
J Hazard Mater ; 416: 126125, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492919

RESUMO

The ongoing COVID-19 pandemic increases the consumption of antimicrobial substances (ABS) due to the unavailability of approved vaccine(s). To assess the effect of imprudent consumption of ABS during the COVID-19 pandemic, we compare the 2020 prevalence of antidrug resistance (ADR) of Escherichia coli (E. coli) with a similar survey carried out in 2018 in Ahmedabad, India using SARS-CoV-2 gene detection as a marker of ABS usage. We found a significant ADR increase in 2020 compared to 2018 in ambient water bodies, harbouring a higher incidence of ADR E.coli towards non-fluoroquinolone drugs. Effective SARS-CoV-2 genome copies were found to be associated with the ADR prevalence. The prevalence of ADR depends on the efficiency of WWTPs (Wastewater Treatment Plants) and the catchment area in its vicinity. In the year 2018 study, prevalence of ADR was discretely distributed, and the maximum ADR prevalence recorded was ~60%; against the current homogenous ADR increase, and up to 85% of maximum ADR among the incubated E.coli isolated from the river (Sabarmati) and lake (Chandola and Kankaria) samples. Furthermore, wastewater treatment plants showed less increase in comparison to the ambient waters, which eventually imply that although SARS-CoV-2 genes and faecal pollution may be diluted in the ambient waters, as indicated by low Ct-value and E.coli count, the danger of related aftermath like ADR increase cannot be nullified. Also, Non-fluoroquinolone drugs exhibited overall more resistance than quinolone drugs. Overall, this is probably the first-ever study that traces the COVID-19 pandemic imprints on the prevalence of antidrug resistance (ADR) through wastewater surveillance and hints at monitoring escalation of other environmental health parameters. This study will make the public and policyholders concerned about the optimum use of antibiotics during any kind of treatment.


Assuntos
COVID-19 , Escherichia coli/genética , Humanos , Pandemias , SARS-CoV-2 , Águas Residuárias
3.
Sci Rep ; 11(1): 14115, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239000

RESUMO

Excessive ingestion of fluorides might adversely affect the health of humans. Hence, this study aimed to investigate the concentrations of infusible fluoride in five different types of tea and herbal products; additionally, the probabilistic health risks associated with the ingestion of fluoride in drinking tea and herbal products were estimated. The highest and lowest concentrations of infusible fluoride were detected in black and white tea, respectively. On average, the highest amount of infusible fluoride was extracted following a short brewing time of 5 min in the case of black tea (2.54 mg/L), herbal tea (0.40 mg/L), and white tea (0.21 mg/L). The level of infusible fluoride during brewing was inversely associated with the leaf size of the tea and herbal products. Furthermore, the type of water used influenced the release of infusible fluoride; purified water yielded lower amounts of infused fluoride. The findings of the probabilistic health risk assessment indicated that the consumption of black tea can increase the fluoride intake leading to chronic exposure. Thus, the health risk posed by fluoride intake from drinking tea needs to be evaluated in more details in the future. Appropriate measures for health risk mitigation need to be implemented to minimize the total body burden of fluorides in humans.


Assuntos
Fluoretos/análise , Probabilidade , Medição de Risco , Chá/química , Chás de Ervas/análise , Adolescente , Adulto , Criança , Humanos , Folhas de Planta/anatomia & histologia , Fatores de Tempo , Incerteza , Água
4.
Chem Eng J ; 425: 130635, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34149304

RESUMO

In the initial pandemic phase, effluents from wastewater treatment facilities were reported mostly free from Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) RNA, and thus conventional wastewater treatments were generally considered effective. However, there is a lack of first-hand data on i) comparative efficacy of various treatment processes for SARS-CoV-2 RNA removal; and ii) temporal variations in the removal efficacy of a given treatment process in the backdrop of active COVID-19 cases. This work provides a comparative account of the removal efficacy of conventional activated sludge (CAS) and root zone treatments (RZT) based on weekly wastewater surveillance data, consisting of forty-four samples, during a two-month period. The average genome concentration was higher in the inlets of CAS-based wastewater treatment plant (WWTP) in the Sargasan ward (1.25 × 103 copies/ L), than that of RZT-based WWTP (7.07 × 102 copies/ L) in an academic institution campus of Gandhinagar, Gujarat, India. ORF 1ab and S genes appeared to be more sensitive to treatment i.e., significantly reduced (p < 0.05) than N genes (p > 0.05). CAS treatment exhibited better RNA removal efficacy (p = 0.014) than RZT (p = 0.032). Multivariate analyses suggested that the effective genome concentration should be calculated based on the presence/absence of multiple genes. The present study stresses that treated effluents are not always free from SARS-CoV-2 RNA, and the removal efficacy of a given WWTP is prone to exhibit temporal variability owing to variations in active COVID-19 cases in the vicinity and genetic material accumulation over the time. Disinfection seems less effective than the adsorption and coagulation processes for SARS-CoV-2 removal. Results stress the need for further research on mechanistic insight on SARS-CoV-2 removal through various treatment processes taking solid-liquid partitioning into account.

5.
JCI Insight ; 6(10)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-33857021

RESUMO

Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the US Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevented the dyskinesia induced by dopamine D2 receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1). In mice, haloperidol-induced VCMs were also mitigated by treatment with AM404 applied to the dorsal striatum, an effect not seen in TRPV1-deficient mice. Acetaminophen prevented the haloperidol-induced decrease in the number of c-Fos+preproenkephalin+ striatal neurons in wild-type mice but not in TRPV1-deficient mice. Finally, chemogenetic stimulation of indirect pathway medium spiny neurons in the dorsal striatum decreased haloperidol-induced VCMs. These results suggest that acetaminophen activates the indirect pathway neurons by activating TRPV1 channels via AM404.

6.
J Hazard Mater ; 411: 125183, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-33858117

RESUMO

In April 2016, a series of earthquakes (M 7.3 on the Japan Meteorological Agency scale) occurred in Kumamoto, Japan causing serious damage to underground sewerage networks. In this study, we evaluated sewer exfiltration in groundwater in the Kumamoto area after the earthquakes by using multiple tracers. We used 14 pharmaceuticals, including carbamazepine and crotamiton, and anthropogenic Gd as tracers, and we measured concentrations of these tracers from September 2016 to November 2017 seasonally. The detection frequency of caffeine, carbamazepine, crotamiton, ibuprofen, and anthropogenic Gd ranged from 29% to 45%, and the concentrations of the pharmaceuticals in the groundwater were lower than those in previous studies. The median of all pharmaceutical concentrations did not decrease, whereas the median of the sum of crotamiton and carbamazepine concentrations, which are quantitative sewage markers, decreased with time. The sewer exfiltration rates in September 2016 estimated using carbamazepine, crotamiton, and anthropogenic Gd were 0.59 ± 0.27%, 0.66 ± 0.47%, and 0.11 ± 0.18% of sewage dry weather flow, respectively, indicating that the effect of the earthquakes on sewer exfiltration was small, probably because the damaged sewers were quickly repaired. This study demonstrated that a multiple-tracer approach is useful for evaluating sewer exfiltration after major earthquakes.


Assuntos
Terremotos , Água Subterrânea , Preparações Farmacêuticas , Japão , Esgotos/análise , Eliminação de Resíduos Líquidos
7.
Sci Total Environ ; 776: 145740, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33647647

RESUMO

Antiviral drugs have been used to treat the ever-growing number of coronavirus disease, 2019 (COVID-19) patients. Consequently, unprecedented amounts of such drug residues discharging into ambient waters raise concerns on the potential ecotoxicological effects to aquatic lives, as well as development of antiviral drug-resistance in wildlife. Here, we estimated the occurrence, fate and ecotoxicological risk of 11 therapeutic agents suggested as drugs for COVID-19 treatment and their 13 metabolites in wastewater and environmental waters, based on drug consumption, physical-chemical property, and ecotoxicological and pharmacological data for the drugs, with the aid of quantitative structure-activity relationship (QSAR) modelling. Our results suggest that the removal efficiencies at conventional wastewater treatment plants will remain low (<20%) for half of the substances, and consequently, high drug residues (e.g. 7402 ng/L ribavirin, 4231 ng/L favipiravir, 730 ng/L lopinavir, 319 ng/L remdesivir; each combined for both unchanged forms and metabolites; and when each drug is administered to 100 patients out of 100,000 populations on a day) can be present in secondary effluents and persist in the environmental waters. Ecotoxicological risk in receiving river waters can be high (risk quotient >1) by a use of favipiravir, lopinavir, umifenovir and ritonavir, and medium (risk quotient >0.1) by a use of chloroquine, hydroxychloroquine, remdesivir, and ribavirin, while the risk will remain low (risk quotient <0.1) for dexamethasone and oseltamivir. The potential of wild animals acquiring antiviral drug resistance was estimated to be low. Our prediction suggests a pressing need for proper usage and waste management of antiviral drugs as well as for improving removal efficiencies of drug residues in wastewater.


Assuntos
COVID-19 , Coronavirus , Animais , Antivirais/toxicidade , COVID-19/tratamento farmacológico , Humanos , SARS-CoV-2
8.
Sci Total Environ ; 754: 142329, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33254951

RESUMO

For the first time, we present, i) an account of decay in the genetic material loading of SARS-CoV-2 during Upflow Anaerobic Sludge Blanket (UASB) treatment of wastewater, and ii) comparative evaluation of polyethylene glycol (PEG), and ultrafiltration as virus concentration methods from wastewater for the quantification of SARS-CoV-2 genes. The objectives were achieved through tracking of SARS-CoV-2 genetic loadings i.e. ORF1ab, N and S protein genes on 8th and 27th May 2020 along the wastewater treatment plant (106000 m3 million liters per day) equipped with UASB system in Ahmedabad, India. PEG method performed better in removing materials inhibiting RT-qPCR for SARS-CoV-2 gene detection from the samples, as evident from constant and lower CT values of control (MS2). Using the PEG method, we found a reduction >1.3 log10 reduction in SARS-CoV-2 RNA abundance during UASB treatment, and the RNA was not detected at all in the final effluent. The study implies that i) conventional wastewater treatment systems is effective in SARS-CoV-2 RNA removal, and ii) UASB system significantly reduces SARS-CoV-2 genetic loadings. Finally, PEG method is recommended for better sensitivity and inhibition removal during SARS-CoV-2 RNA quantification in wastewater.


Assuntos
COVID-19 , Esgotos , Águas Residuárias , Anaerobiose , Reatores Biológicos , Humanos , Índia , Pandemias , RNA , Eliminação de Resíduos Líquidos
9.
J Hazard Mater ; 405: 124043, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33268203

RESUMO

In this review, we present the environmental perspectives of the viruses and antiviral drugs related to SARS-CoV-2. The present review paper discusses occurrence, fate, transport, susceptibility, and inactivation mechanisms of viruses in the environment as well as environmental occurrence and fate of antiviral drugs, and prospects (prevalence and occurrence) of antiviral drug resistance (both antiviral drug resistant viruses and antiviral resistance in the human). During winter, the number of viral disease cases and environmental occurrence of antiviral drug surge due to various biotic and abiotic factors such as transmission pathways, human behaviour, susceptibility, and immunity as well as cold climatic conditions. Adsorption and persistence critically determine the fate and transport of viruses in the environment. Inactivation and disinfection of virus include UV, alcohol, and other chemical-base methods but the susceptibility of virus against these methods varies. Wastewater treatment plants (WWTPs) are major reserviors of antiviral drugs and their metabolites and transformation products. Ecotoxicity of antiviral drug residues against aquatic organisms have been reported, however more threatening is the development of antiviral resistance, both in humans and in wild animal reservoirs. In particular, emergence of antiviral drug-resistant viruses via exposure of wild animals to high loads of antiviral residues during the current pandemic needs further evaluation.


Assuntos
Antivirais , Farmacorresistência Viral/efeitos dos fármacos , Microbiologia Ambiental , Poluentes Ambientais , SARS-CoV-2 , Inativação de Vírus , Adsorção , Animais , Antivirais/química , Antivirais/uso terapêutico , Antivirais/toxicidade , Organismos Aquáticos/efeitos dos fármacos , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , COVID-19/etiologia , Ecotoxicologia , Poluentes Ambientais/química , Poluentes Ambientais/uso terapêutico , Poluentes Ambientais/toxicidade , Humanos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Estações do Ano , Inativação de Vírus/efeitos dos fármacos , Inativação de Vírus/efeitos da radiação , Purificação da Água
10.
Neurochem Int ; 143: 104935, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33301817

RESUMO

The nucleus accumbens (NAc) plays a crucial role in various mental activities, including positive and negative reinforcement. We previously hypothesized that a balance between dopamine (DA) and adenosine signals regulates the PKA-Rap1 pathway in medium spiny neurons expressing DA D1 receptors (D1R-MSNs) or D2 receptors (D2R-MSNs) and demonstrated that the PKA-Rap1 pathway in D1R-MSNs is responsible for positive reinforcement. Here, we show the role of the PKA-Rap1 pathway in accumbal D2R-MSNs in negative reinforcement. Mice were exposed to electric foot shock as an aversive stimulus. We monitored the phosphorylation level of Rap1gap S563, which leads to the activation of Rap1. Electric foot shocks increased the phosphorylation level of GluN1 S897 and Rap1gap S563 in the NAc. The aversive stimulus-evoked phosphorylation of Rap1gap S563 was detected in accumbal D2R-MSNs and inhibited by pretreatment with adenosine A2a receptor (A2aR) antagonist. A2aR antagonist-treated mice showed impaired aversive memory in passive avoidance tests. AAV-mediated inhibition of PKA, Rap1, or MEK1 in accumbal D2R-MSNs impaired aversive memory in passive avoidance tests, whereas activation of this pathway potentiated aversive memory. Optogenetic inactivation of mesolimbic DAergic neurons induced place aversion in real-time place aversion tests. Aversive response was attenuated by inhibition of PKA-Rap1 signaling in accumbal D2R-MSNs. These results suggested that accumbal D2R-MSNs regulate aversive behaviors through the A2aR-PKA-Rap1-MEK pathway. Our findings provide a novel molecular mechanism for regulating negative reinforcement.


Assuntos
Aprendizagem da Esquiva/fisiologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Neurônios/metabolismo , Núcleo Accumbens/metabolismo , Receptores de Dopamina D2/metabolismo , Proteínas rap1 de Ligação ao GTP/metabolismo , Antagonistas do Receptor A2 de Adenosina/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Estimulação Elétrica/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Purinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
11.
Curr Pollut Rep ; : 1-12, 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-32953402

RESUMO

Prevalence of SARS-CoV-2 in the aquatic environment pertaining to the COVID-19 pandemic has been a global concern. Though SARS-CoV-2 is known as a respiratory virus, its detection in faecal matter and wastewater demonstrates its enteric involvement resulting in vulnerable aquatic environment. Here, we provide the latest updates on wastewater-based epidemiology, which is gaining interest in the current situation as a unique tool of surveillance and monitoring of the disease. Transport pathways with its migration through wastewater to surface and subsurface waters, probability of infectivity and ways of inactivation of SARS-CoV-2 are discussed in detail. Epidemiological models, especially compartmental projections, have been explained with an emphasis on its limitation and the assumptions on which the future predictions of disease propagation are based. Besides, this review covers various predictive models to track and project disease spread in the future and gives an insight into the probability of a future outbreak of the disease.

12.
Transl Psychiatry ; 10(1): 247, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32699248

RESUMO

Schizophrenia (SCZ) is known to be a heritable disorder; however, its multifactorial nature has significantly hampered attempts to establish its pathogenesis. Therefore, in this study, we performed genome-wide copy-number variation (CNV) analysis of 2940 patients with SCZ and 2402 control subjects and identified a statistically significant association between SCZ and exonic CNVs in the ARHGAP10 gene. ARHGAP10 encodes a member of the RhoGAP superfamily of proteins that is involved in small GTPase signaling. This signaling pathway is one of the SCZ-associated pathways and may contribute to neural development and function. However, the ARHGAP10 gene is often confused with ARHGAP21, thus, the significance of ARHGAP10 in the molecular pathology of SCZ, including the expression profile of the ARHGAP10 protein, remains poorly understood. To address this issue, we focused on one patient identified to have both an exonic deletion and a missense variant (p.S490P) in ARHGAP10. The missense variant was found to be located in the RhoGAP domain and was determined to be relevant to the association between ARHGAP10 and the active form of RhoA. We evaluated ARHGAP10 protein expression in the brains of reporter mice and generated a mouse model to mimic the patient case. The model exhibited abnormal emotional behaviors, along with reduced spine density in the medial prefrontal cortex (mPFC). In addition, primary cultured neurons prepared from the mouse model brain exhibited immature neurites in vitro. Furthermore, we established induced pluripotent stem cells (iPSCs) from this patient, and differentiated them into tyrosine hydroxylase (TH)-positive neurons in order to analyze their morphological phenotypes. TH-positive neurons differentiated from the patient-derived iPSCs exhibited severe defects in both neurite length and branch number; these defects were restored by the addition of the Rho-kinase inhibitor, Y-27632. Collectively, our findings suggest that rare ARHGAP10 variants may be genetically and biologically associated with SCZ and indicate that Rho signaling represents a promising drug discovery target for SCZ treatment.


Assuntos
Esquizofrenia , Animais , Variações do Número de Cópias de DNA , Proteínas Ativadoras de GTPase/genética , Humanos , Camundongos , Esquizofrenia/genética , Transdução de Sinais , Proteína rhoA de Ligação ao GTP
15.
Groundw Sustain Dev ; 11: 100400, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32322654

RESUMO

To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer compared to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.

16.
J Hazard Mater Lett ; 1: 100001, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34977840

RESUMO

Increased concern has recently emerged pertaining to the occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in aquatic environment during the current coronavirus disease 2019 (COVID-19) pandemic. While infectious SARS-CoV-2 has yet to be identified in the aquatic environment, the virus potentially enters the wastewater stream from patient excretions and a precautionary approach dictates evaluating transmission pathways to ensure public health and safety. Although enveloped viruses have presumed low persistence in water and are generally susceptible to inactivation by environmental stressors, previously identified enveloped viruses persist in the aqueous environment from days to several weeks. Our analysis suggests that not only the surface water, but also groundwater, represent SARS-CoV-2 control points through possible leaching and infiltrations of effluents from health care facilities, sewage, and drainage water. Most fecally transmitted viruses are highly persistent in the aquatic environment, and therefore, the persistence of SARS-CoV-2 in water is essential to inform its fate in water, wastewater and groundwater and subsequent human exposure.

17.
Cell Rep ; 29(10): 3235-3252.e9, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31801086

RESUMO

Dopamine (DA) activates mitogen-activated protein kinase (MAPK) via protein kinase A (PKA)/Rap1 in medium spiny neurons (MSNs) expressing the dopamine D1 receptor (D1R) in the nucleus accumbens (NAc), thereby regulating reward-related behavior. However, how MAPK regulates reward-related learning and memory through gene expression is poorly understood. Here, to identify the relevant transcriptional factors, we perform proteomic analysis using affinity beads coated with cyclic AMP response element binding protein (CREB)-binding protein (CBP), a transcriptional coactivator involved in reward-related behavior. We identify more than 400 CBP-interacting proteins, including Neuronal Per Arnt Sim domain protein 4 (Npas4). We find that MAPK phosphorylates Npas4 downstream of PKA, increasing the Npas4-CBP interaction and the transcriptional activity of Npas4 at the brain-derived neurotrophic factor (BDNF) promoter. The deletion of Npas4 in D1R-expressing MSNs impairs cocaine-induced place preference, which is rescued by Npas4-wild-type (WT), but not by a phospho-deficient Npas4 mutant. These observations suggest that MAPK phosphorylates Npas4 in D1R-MSNs and increases transcriptional activity to enhance reward-related learning and memory.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Expressão Gênica/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fosforilação/fisiologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células COS , Linhagem Celular , Chlorocebus aethiops , Cocaína/farmacologia , Dopamina/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação/efeitos dos fármacos , Proteômica/métodos , Receptores de Dopamina D1/metabolismo , Recompensa , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Transcrição Genética/efeitos dos fármacos , Transcrição Genética/fisiologia
18.
Sci Total Environ ; 692: 903-916, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539995

RESUMO

Land abandonment, e.g. agricultural land abandonment, can result in various social and ecological impacts. It would thus be helpful if the extent and spatial pattern of future land abandonment could be projected. However, the trajectory of future land abandonment generally depends on various factors, including biophysical conditions and future changes in socioeconomic indicators in the area. In this study, we developed a general framework for a scenario-based land abandonment projection, featuring a coupled regional economic and spatially explicit land change modeling approach. We applied this framework in selected municipalities in Fukushima Prefecture, Japan, under two socioeconomic development scenarios (2014-2050): low population and economic growth (LL scenario) and high population and economic growth (HH scenario). The case study results, which are also visualized through a set of hot spot maps, revealed that agricultural land abandonment would be more intense under the HH scenario due to the much higher future decline in farmer population driven by the shift in people's employment and main source of livelihood. Under the LL scenario, residential and urban land abandonment would be more profound because of the much higher future decline in total population. In general, our results provide insights into some plausible future socioeconomic changes, their interplay and their consequent land abandonment in the case study area, which would be useful in the context of forward-looking adaptive development planning. The proposed framework can be applied to other case study areas.

19.
Sci Total Environ ; 689: 843-853, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31280166

RESUMO

We investigated the multimedia fate of decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) in the densely populated catchment basin of Tokyo Bay, Japan, by using a georeferenced multimedia model. We estimated the daily per person consumption rate of these compounds in Japan according to literature. Emissions to the atmosphere accounted for almost all of the emissions of these compounds to the environment. The majority of these compounds was predicted to be distributed in the atmosphere (about 60%) and sediment (about 40%). The advective flows in and out of the atmosphere over the Tokyo Bay catchment basin dominated the flows of these compounds. The sewerage systems contributed considerably to the transport and fate of D5 and D6 in water. They transported these compounds from households to discharge outlets of sewage treatment plants (STPs), which in turn accounted for approximately one quarter of the emission of these compounds to rivers and to Tokyo Bay. The wastewater treatment plants also effectively removed these compounds from the wastewater. The overall persistence of D5 and D6 in the catchment basin was estimated to be 3.8-9.5 days. The horizontal distributions of these compounds were similar among environmental compartments; high concentrations were generally observed in populated areas. A sensitivity analysis demonstrated that the D5 discharge rate to Tokyo Bay excluding the direct discharge from STPs and the D5 mass in the river compartment were sensitive to changes of the organic-carbon-water partition coefficient. Comparison with the concentrations in rivers measured recently in the target area showed that the model captured overall trends of low to high concentrations in rivers. However, there was some variability and a bias toward underprediction. The model provided a better fit to measurements for D5 than for D6. One potential factor contributing to the bias toward underprediction was underestimation of the consumption rates.

20.
Neurochem Int ; 122: 8-18, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30336179

RESUMO

Medium spiny neurons (MSNs) expressing dopamine D1 receptor (D1R) or D2 receptor (D2R) are major components of the striatum. Stimulation of D1R activates protein kinase A (PKA) through Golf to increase neuronal activity, while D2R stimulation inhibits PKA through Gi. Adenosine A2A receptor (A2AR) coupled to Golf is highly expressed in D2R-MSNs within the striatum. However, how dopamine and adenosine co-operatively regulate PKA activity remains largely unknown. Here, we measured Rap1gap serine 563 phosphorylation to monitor PKA activity and examined dopamine and adenosine signals in MSNs. We found that a D1R agonist increased Rap1gap phosphorylation in striatal slices and in D1R-MSNs in vivo. A2AR agonist CGS21680 increased Rap1gap phosphorylation, and pretreatment with the D2R agonist quinpirole blocked this effect in striatal slices. D2R antagonist eticlopride increased Rap1gap phosphorylation in D2R-MSNs in vivo, and the effect of eticlopride was blocked by the pretreatment with the A2AR antagonist SCH58261. These results suggest that adenosine positively regulates PKA in D2R-MSNs through A2AR, while this effect is blocked by basal dopamine in vivo. Incorporating computational model analysis, we propose that the shift from D1R-MSNs to D2R-MSNs or vice versa appears to depend predominantly on a change in dopamine concentration.


Assuntos
Adenosina/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Transdução de Sinais , Animais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Agonistas de Dopamina/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Receptores de Dopamina D1/metabolismo , Proteínas rap1 de Ligação ao GTP/metabolismo
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