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This paper estimated the impact of intervention effects (state of emergency (SOE) or quasi-SOE requirements) and information effects (publicized increases in the number of coronavirus disease 2019 (COVID-19) deaths and fear of infection) on preventive behaviors and telecommuting during the COVID-19 pandemic using the Japan Household Panel Survey. Our results indicated that SOEs and quasi-SOEs had positive effects on the adoption of preventive behaviors among individuals, including handwashing, which indicates that an SOE has a direct effect and an indirect effect. Although SOEs in Japan were less enforceable and more lenient than those in other countries, they still had a certain effect on people's adoption of preventive behaviors. However, the contribution of information effects was much larger than that of intervention effects, suggesting the importance of how and when information should be communicated to the public to prevent the spread of infection.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , SARS-CoV-2 , Japón/epidemiología , Desinfección de las ManosRESUMEN
As the properties of graphene films depend on their stacked atomic layers, their thickness should be accurately controlled to improve their specific properties. However, by existing methods, controlling the homogeneity of graphene films at the atomic level remains difficult. In this work, photo-stimulated structural modifications of few-layer graphene epitaxially grown on 4H-SiC(0001) were studied using Raman scattering spectroscopy and core-level photoemission spectroscopy. Iterative excitation with laser pulses (800nm, 100fs, p-polarized, 250mJ/cm2) changed the graphene-related 2D Raman line, which is composed of three components characterized by their different responses upon photoexcitation: two components decaying at fast and slow rates, and a component highly resistant to excitation. Core-level photoemission spectroscopy revealed that the observed decay of the 2D line was associated with the elimination of carbon atoms from the graphene layers, finally leaving the robust thin film of single-layer graphene by prolonged excitation. Therefore, this work clearly demonstrates the thickness-dependent structural stability of graphene to optical excitation and opens a promising new method for thinning graphene. An underlying mechanism for the photo-stimulated modifications was also proposed.
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Along with the great interest in two-dimensional elemental materials that has emerged in recent years, atomically thin layers of bismuth have attracted attention due to physical properties on account of a strong spin-orbit coupling. Thickness dependent electronic band structure must be explored over the whole Brillouin zone in order to further explore their topological electronic properties. The anisotropic band structures along zig-zag and armchair directions of α-bismuthene (α-Bi) were resolved using the two-dimensional mapping of angle-resolved photoemission spectra. An increase in the number of layers from 1- to 2-bilayers (BLs) shifts the top of a hole band onΓ¯-X¯1line to high wavenumber regions. Subsequently, an electron pocket onΓ¯-X¯1line and a hole pocket centred atΓ¯point appears in the 3 BL α-Bi. Gapless Dirac-cone features with a large anisotropy were clearly resolved onX¯2point in the 1-BL and 2-BL α-Bi, which can be attributed to the strong spin-orbit coupling and protection by the nonsymmorphic symmetry of the α-Bi lattice.
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Spatially controlling the Fermi level of topological insulators and keeping their electronic states stable are indispensable processes to put this material into practical use for semiconductor spintronics devices. So far, however, such a method has not been established yet. Here we show a novel method for doping a hole into n-type topological insulators Bi2X3 (X= Se, Te) that overcomes the shortcomings of the previous reported methods. The key of this doping is to adsorb H2O on Bi2X3 decorated with a small amount of carbon, and its trigger is the irradiation of a photon with sufficient energy to excite the core electrons of the outermost layer atoms. This method allows controlling the doping amount by the irradiation time and acts as photolithography. Such a tunable doping makes it possible to design the electronic states at the nanometer scale and, thus, paves a promising avenue toward the realization of novel spintronics devices based on topological insulators.
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We report the complete genome sequence of Bifidobacterium longum subsp. longum JCM7052, isolated from human feces in Japan. This strain has the capability of growing on and utilizing gum arabic as an energy source. The complete genome is 2,273,627 bp long, with 1,929 protein-coding genes and 59.9 mol% G+C content.
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Owing to the rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic worldwide, individuals experience considerable psychological distress daily. The present study aimed to clarify the prevalence of psychological distress and determine the population most affected by risk factors such as the pandemic, socioeconomic status (SES), and lifestyle-related factors causing psychological distress in the early phases of the pandemic in Japan. This study was conducted via a web-based survey using quota sampling to ensure representativeness of the Japanese population aged 20-64 years. A cross-sectional study of 11,342 participants (5,734 males and 5,608 females) was conducted using a self-administered questionnaire that included the Japanese version of the Kessler 6 Psychological Distress Scale (K6) and questions related to the pandemic, SES, and lifestyle. The prevalence of psychological distress, represented by a K6 score of 5 or more, was 50.3% among males and 52.6% among females. Both males and females with annual household incomes less than 2 million yen and males aged in their twenties had significantly higher K6 scores than those with annual household incomes above 2 million yen and males aged over 30 years. Binary logistic regression analyses found pandemic-related factors such as medical history, inability to undergo clinical tests immediately, having trouble in daily life, unavailability of groceries, new work style, and vague anxiety; SES-related factors such as lesser income; and lifestyle-related factors such as insufficient rest, sleep, and nutritious meals to be significantly related to psychological distress. Psychological distress was more prevalent among people with low income and in younger generations than among other groups. There is an urgent need to provide financial, medical, and social support to those affected by the coronavirus disease 2019 (COVID-19) pandemic.
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Ansiedad/psicología , COVID-19/psicología , Salud Mental/estadística & datos numéricos , Pandemias/estadística & datos numéricos , Adulto , COVID-19/epidemiología , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Distrés Psicológico , SARS-CoV-2/patogenicidad , Apoyo Social , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The association of socioeconomic status and lifestyle behaviours on mental health appears well-established in the literature, as several studies report that better socioeconomic status such as higher levels of disposable income and employment as well as practising healthy lifestyles can enhance mental well-being. However, the reliance on cross-sectional correlations and lack of adequate statistical controls are possible limitations. This study aims to add the evidence of longitudinal association to the literature by using Japanese representative longitudinal household panel data. We employed panel data analytical techniques such as the random-effects conditional logistic regression (RE-CLR) and the fixed-effects conditional logistic regression (FE-CLR) models with possible time variant confounders being controlled. Our sample was comprised of 14,717 observations of 3,501 individuals aged 22-59 years for five waves of the Japanese Household Panel Survey. We confirmed many of the factors associated with mental health reported in existing studies by analysing cross-sectional data. These significant associations are also longitudinal (within) associations estimated by the FE-CLR models. Such factors include unemployment, low household income, short nightly sleeping duration, and lack of exercise. However, we also found that several factors such as disposable income, living alone, and drinking habits are not significantly associated with mental health in the FE-CRL models. The results imply the reverse causality that poor mental health conditions cause lower disposal income, possibly due to the inability to exhibit higher productivity, but an increase in disposal income would not necessarily improve mental health conditions. In this case, aggressive policy interventions to increase the disposal income of people of lower socioeconomic backgrounds would not necessarily be effective to minimize health inequalities.
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Estilo de Vida , Salud Mental/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Clase Social , Encuestas y Cuestionarios , Adulto JovenAsunto(s)
Betacoronavirus , Infecciones por Coronavirus , Neumonía Viral , COVID-19 , Humanos , Pandemias , SARS-CoV-2RESUMEN
The Japanese government instituted countermeasures against COVID-19, a pneumonia caused by the new coronavirus, in January 2020. Seeking "people's behavioral changes," in which the government called on the public to take precautionary measures or exercise self-restraint, was one of the important strategies. The purpose of this study is to investigate how and from when Japanese citizens have changed their precautionary behavior under circumstances in which the government has only requested their cooperation. This study uses micro data from a cross-sectional survey conducted on an online platform of an online research company, based on quota sampling that is representative of the Japanese population. By the end of March 2020, a total of 11,342 respondents, aged from 20 to 64 years, were recruited. About 85 percent reported practising the social distancing measures recommended by the government including more females than males and more older than younger participants. Frequent handwashing is conducted by 86 percent of all participants, 92 percent of female, and 87.9 percent of over-40 participants. The most important event influencing these precautionary actions was the infection aboard the Diamond Princess cruise ship, which occurred in early February 2020 (23 percent). Information from the central and local governments, received by 60 percent of the participants, was deemed trustworthy by 50 percent. However, the results also showed that about 20 percent of the participants were reluctant to implement proper prevention measures. The statistical analysis indicated that the typical characteristics of those people were male, younger (under 30 years old), unmarried, from lower-income households, a drinking or smoking habit, and a higher extraversion score. To prevent the spread of infection in Japan, it is imperative to address these individuals and encourage their behavioural changes using various means to reach and influence them.
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Conducta , Control de Enfermedades Transmisibles/estadística & datos numéricos , Infecciones por Coronavirus/prevención & control , Adhesión a Directriz/estadística & datos numéricos , Pandemias/prevención & control , Neumonía Viral/prevención & control , Adulto , Betacoronavirus , COVID-19 , Estudios Transversales , Femenino , Gobierno , Desinfección de las Manos , Humanos , Japón , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: There is rising public concern over the widening health inequalities in many countries. The aim of this study was to clarify the associations of socioeconomic status (SES)-related variables, such as levels of household disposable income and employment status, and lifestyle factors with mental health conditions among Japanese adults aged 40 to 69. METHODS: A cross-sectional study of 3085 participants (1527 males and 1558 females) was undertaken by using a self-administered questionnaire that included the Japanese version of the 12-item General Health Questionnaire (GHQ-12) and questions related to socioeconomic and lifestyle factors. RESULTS: The prevalence of poor mental health conditions, represented by a GHQ-12 score of 4 or more, was 33.4% among males and 40.4% among females. Males whose annual household disposable income was less than 2 million yen had significantly higher GHQ-12 scores than those with an annual household disposable income above 2 million yen. As per binary logistic regression analyses, short sleep duration and the absence of physical exercise were significantly related to poor mental health conditions among both males and females. Among females, a household disposable income of less than 2 million yen could be a risk factor for poor mental health conditions. Age and habitual drinking were inversely associated with poor mental health conditions. CONCLUSIONS: Low levels of household disposable income and unhealthy lifestyle factors were significantly associated with mental health conditions. These results suggest the importance of improving unhealthy lifestyle behaviours and developing effective health promotion programmes. In addition, there is a need for social security systems for people from different socioeconomic backgrounds.
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Disparidades en el Estado de Salud , Trastornos Mentales/epidemiología , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Japón/epidemiología , Estilo de Vida , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Factores Socioeconómicos , Encuestas y CuestionariosRESUMEN
BACKGROUND: We have previously reported that mRNA expression of chemotaxis- and angiogenesis-related factors in human monocytes increased following interaction with colon cancer cells. Recently, it was also reported that mRNA expression of the chemotaxis-related factor, monocyte chemotactic protein (MCP)-1, in mouse macrophages following treatment with low-dose lipopolysaccharide (LPS) was significantly lower compared to that following treatment with high-dose LPS, and that low-dose LPS failed to activate the classical nuclear factor (NF)-κB pathway. In the present study, we examined changes in mRNA expression of chemotaxis- and angiogenesis-related factors in human monocytes following low-dose LPS treatment and subsequent interaction with colon cancer cells. MATERIALS AND METHODS: The human monocyte cell line THP-1 was treated with LPS and subsequently co-cultured with the human colon cancer cell line DLD-1. mRNA expression was analyzed by quantitative real-time PCR. RESULTS: mRNA expression of MCP-1, vascular endothelial growth factor (VEGF)-A, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-8 in THP-1 cells treated with low-dose LPS (100 pg/ml) decreased compared to untreated THP-1 cells after five days of co-culture with DLD-1 cells. CONCLUSION: mRNA expression of chemotaxis- and angiogenesis-related factors in human monocytes following interaction with colon cancer cells is suppressed by prior treatment with low-dose LPS. Thus, low-dose LPS treatment of human monocytes may be useful for prevention and therapy of colon cancer.
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Comunicación Celular , Quimiocina CCL2/genética , Neoplasias del Colon/terapia , Lipopolisacáridos/farmacología , Monocitos/fisiología , Neoplasias del Colon/patología , Humanos , Interleucina-8/genética , ARN Mensajero/análisis , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
BACKGROUND: In tumors, monocytes differentiate into tumor-associated macrophages following interaction with cancer cells. We have previously reported that angiogenesis- and chemotaxis-related factors are associated with human monocyte differentiation following interaction with colon cancer cells. However, the exact nature of factors remains unknown. We investigated factors associated with differentiation of human colon cancer cells following interaction with monocytes. MATERIALS AND METHODS: The human colon cancer cell line DLD-1 was co-cultured with the human monocyte cell line THP-1. mRNA expression was analyzed by quantitative real-time PCR. RESULTS: Expression of interleukin-1ß, matrix metalloproteinase (MMP)-1, MMP-2, and MMP-3 increased in human colon cancer cells after co-culture with monocytes. Conversely, the expression of monocyte chemotactic protein-1, tumor necrosis factor-α, and signal transducer and activator of transcription-3 did not increase. CONCLUSION: Differentiation of human colon cancer cells following interaction with monocytes may be associated with angiogenesis and metastasis but not chemotaxis and signaling pathways. Thus, angiogenesis- and metastasis-related factors associated with differentiation of human colon cancer cells may constitute important targets for colon cancer therapy.
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Biomarcadores de Tumor/metabolismo , Diferenciación Celular , Neoplasias del Colon/patología , Macrófagos/patología , Monocitos/patología , Neovascularización Patológica/patología , Transducción de Señal , Biomarcadores de Tumor/genética , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Quimiotaxis , Técnicas de Cocultivo , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Monocitos/metabolismo , Metástasis de la Neoplasia , Neovascularización Patológica/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
UNLABELLED: Monocytes are known to differentiate into tissue-specific macrophages in response to the tissue environment, and it has been suggested that tumor-associated macrophages might promote angiogenesis. Therefore, the factors associated with monocyte differentiation into tumor-associated macrophages may become new targets for cancer therapy. However, these factors remain unclear in human colon cancer. The aim of this study was to identify the factors associated with human monocyte differentiation into tumor-associated macrophages at human colon cancer sites. MATERIALS AND METHODS: A human monocyte cell line (THP-1) was co-cultured with a human colon cancer cell line (DLD-1) and mRNA expression was analyzed by quantitative real-time PCR. RESULTS: In THP-1 cells, monocyte chemotactic protein (MCP)-1 mRNA expression increased in a time-dependent manner from day 3 after co-culture with DLD-1 cells; furthermore, expression of vascular endothelial growth factor (VEGF)-A, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-8 mRNA was increased from day 5. This increase in mRNA expression in the THP-1 cells was attributable to the presence of the DLD-1 cells. Therefore, MCP-1, VEGF-A, TNF-α, IL-1ß, and IL-8 are suggested to be associated with differentiation of human monocytes into tumor-associated macrophages at human colon cancer sites.
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Neoplasias del Colon/patología , Regulación Neoplásica de la Expresión Génica , Monocitos/metabolismo , ARN Mensajero/biosíntesis , Diferenciación Celular/genética , Línea Celular , Línea Celular Tumoral/metabolismo , Quimiocina CCL2/biosíntesis , Quimiocina CCL2/genética , Técnicas de Cocultivo , Sistemas de Computación , Humanos , Interleucina-1beta/biosíntesis , Interleucina-1beta/genética , Interleucina-8/biosíntesis , Interleucina-8/genética , Macrófagos/citología , Monocitos/citología , Neovascularización Patológica/genética , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genética , Factor A de Crecimiento Endotelial Vascular/biosíntesis , Factor A de Crecimiento Endotelial Vascular/genéticaRESUMEN
AIM: The response to fluoropyrimidine chemotherapeutic drugs is different in individual tumors. Predictive biomarkers of antitumor effects by these drugs are unknown. 5'-Deoxy-5-fluorouridine (5'-DFUR), a fluoro-pyrimidine chemotherapeutic drug, is converted to 5-fluorouracil (5-FU) by pyrimidine nucleoside phosphorylase (PyNPase). It is suggested that 5'-DFUR will efficiently exert antitumor effects via PyNPase in tumor tissues. The change of PyNPase activity in tumor tissues following 5'-DFUR administration may reflect antitumor effects, and may be useful for detecting predictive factors of antitumor effects. The aim of this study was to search for predictive factors of antitumor effects by analyzing the relationship between clinicopathological factors and the change of PyNPase activity in colorectal tumor tissues after preoperative 5'-DFUR administration. PATIENTS AND METHODS: PyNPase activity in colorectal tissues from 45 patients with colorectal tumors was measured using an ELISA method. RESULTS: The reduction rate of PyNPase activity in colorectal tumor tissues after preoperative 5'-DFUR administration was correlated with significant differences in lymphatic invasion, stage, and histologic classification. It is suggested that lymphatic invasion, stage (distant metastasis), and histologic classification may be predictive factors for evaluating antitumor effects and selecting 5-FU-based chemotherapeutic drugs for patients with colorectal tumors.
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Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/enzimología , Floxuridina/administración & dosificación , Pentosiltransferasa/metabolismo , Neoplasias Colorrectales/patología , Humanos , Pirimidina FosforilasasRESUMEN
AIMS: Previously, we have proposed that methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (C677T) could be a risk factor for diabetic retinopathy. To support our suggestion, we examined in detail the association of MTHFR polymorphism with diabetic retinopathy and nephropathy in Japanese type 2 diabetic patients. METHODS: Subjects (n=190) were free of cardiovascular diseases and were not on hemodialysis. Retinopathy was assessed according to fundamental differentiation; nephropathy was determined according to urinary albumin level; and MTHFR genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. We also analyzed how hyperglycemia affected these three conditions in 131 patients with glycosylated hemoglobin > or =6.5% and fasting blood sugar > or =110 mg/dl. RESULTS: The frequency of 677T/677T homozygous subjects with retinopathy was higher than the frequencies of the other two genotypes, and a significant difference was observed in the distribution of the genotypes (677C/677C, 41.9%; 677C/677T, 31.1%; 677T/677T, 61.5%; P<.05). The susceptibility of 677T/677T homozygote to retinopathy approached significance [odds ratio (OR)=2.17; 95% confidence interval (95% CI)=0.87-5.42]. However, in the population with hyperglycemia, the 677T/677T homozygote modified the risk for retinopathy (OR=4.30; 95% CI=1.42-13.1), especially the risk for nonproliferative retinopathy. In contrast, the 677T/677T homozygote did not affect the risk for nephropathy (OR=1.17; 95% CI=0.45-3.05), even in subjects with hyperglycemia (OR=1.50; 95% CI=0.50-4.48). CONCLUSIONS: Our results are highly suggestive of an important role for MTHFR genotype in susceptibility to retinopathy under hyperglycemia, but not to nephropathy. Preventive therapies based on MTHFR polymorphism could delay the onset of retinopathy in type 2 diabetic patients.
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Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/genética , Retinopatía Diabética/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Adulto , Anciano , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/enzimología , Angiopatías Diabéticas/enzimología , Angiopatías Diabéticas/genética , Nefropatías Diabéticas/enzimología , Retinopatía Diabética/enzimología , Retinopatía Diabética/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Hiperglucemia/enzimología , Hiperglucemia/genética , Hipertensión/epidemiología , Hipertensión/genética , Japón , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
In the process of lipolysis, adipocytes are stimulated by catecholamines through beta(1), beta(2), and beta(3) adrenergic receptors (ARs). So far, beta(2) and beta(3) AR polymorphisms have been reported related to obesity. However, the relation of beta(1)AR polymorphisms to obesity has not been evaluated. In the present study, we examined whether betaAR polymorphisms are associated with obesity-related phenotype in type II diabetic patients. Polymorphisms of beta(1)Ser49Gly, beta(1)Arg389Gly, beta(2)Arg16Gly, beta(2)Gln27Glu and beta(3)Trp64Arg were genotyped in 188 type II diabetic patients by PCR-RFLP. Among these polymorphisms, beta(1)Ser49Gly was found to be associated with obesity. Subjects with beta(1)Gly49 allele showed higher body mass index (BMI) than those with Ser49/Ser49 genotype (24.7+/-3.7 vs. 23.4+/-3.3 kg/m(2); p=0.031). Subjects with beta(1)Gly49 allele were more frequently overweight (BMI >or= 25 kg/m(2)) compared with beta(1)Ser49 homozygous group (42.1 vs. 24.4%, p=0.015). By multiple linear regression analysis, beta(1)Ser49Gly polymorphism was independently associated with higher BMI (p=0.019, beta=0.166). Our data indicate that the Gly49 allele in beta(1)AR is associated with higher BMI in type II diabetic patients. Genotyping for beta(1)Ser49Gly polymorphism in type II diabetic patients may have clinical benefit to predict obesity, thereby contributing to the prevention of insulin resistance.
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Diabetes Mellitus Tipo 2/genética , Obesidad/genética , Receptores Adrenérgicos beta 1/genética , Anciano , ADN/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético/genética , Polimorfismo Genético/fisiología , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 3/genética , Análisis de Regresión , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Oxigenasas de Función Mixta/genética , Warfarina/administración & dosificación , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Citocromo P-450 CYP2C9 , Relación Dosis-Respuesta a Droga , Genotipo , Hemorragia/tratamiento farmacológico , Hemorragia/genética , Homocigoto , Humanos , Estereoisomerismo , Vitamina K Epóxido Reductasas , Warfarina/sangre , Warfarina/químicaRESUMEN
A denitrifying phototroph, Rhodobacter sphaeroides f. sp. denitrificans, has the ability to denitrify by respiring nitrate. The periplasmic respiratory nitrate reductase (Nap) catalyses the first step in denitrification and is encoded by the genes, napKEFDABC. By assaying the ss-galactosidase activity of napKEFD-lacZ fusions in wild type and nap mutant cells grown under various growth conditions, the environmental signal for inducing nap expression was examined. Under anoxic conditions with nitrate, nap genes expression in the wild-type strain was highest in the dark, and somewhat lowered by incident light, but that of the napA, napB, and napC mutant strains was low, showing that nap expression is dependent on nitrate respiration. Under oxic conditions, both the wild type and nap mutant cells showed high ss-galactosidase activities, comparable to the wild-type grown under anoxic conditions with nitrate. Myxothiazol, a specific inhibitor of the cytochrome bc (1) complex, did not affect the beta-galactosidase activity in the wild-type cells grown aerobically, suggesting that the redox state of the quinone pool was not a candidate for the activation signal for aerobic nap expression. These results suggested that the trans-acting regulatory signals for nap expression differ between anoxic and oxic conditions. Deletion analysis showed that the nucleotide sequence from -135 to -88 with respect to the translational start point is essential for nap expression either under anoxic or oxic conditions, suggesting that the same cis-acting element is involved in regulating nap expression under either anoxic with nitrate or oxic conditions.
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Aerobiosis/fisiología , Anaerobiosis/fisiología , Genes Bacterianos , Nitrato Reductasas/genética , Nitratos/metabolismo , Rhodobacter sphaeroides/genética , Complejo III de Transporte de Electrones/antagonistas & inhibidores , Eliminación de Gen , Regulación Bacteriana de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Metacrilatos/farmacología , Mutación , Nitrato Reductasas/biosíntesis , Periplasma/enzimología , Regiones Promotoras Genéticas/genética , Proteínas Recombinantes de Fusión/genética , Rhodobacter sphaeroides/enzimología , Rhodobacter sphaeroides/crecimiento & desarrollo , Tiazoles/farmacologíaRESUMEN
Platelet activating factor (PAF) is a key molecule for inflammation. To examine a role of peroxisome proliferator-activated receptor gamma (PPARgamma) in inflammatory reactions of atherosclerosis, we investigated the effects of 15-deoxy-(Delta12,14)-Prostaglandin J2 (15d-PGJ2) and pioglitazone, PPARgamma ligands, on plasma PAF-acetylhydrolase (PAF-AH) expression in THP-1 macrophages. PAF-AH mRNA and protein were up-regulated by the PPARgamma ligands. Prostaglandin F2alpha (PGF2alpha), a PARgamma inhibitor, abrogated the up-regulation of PAF-AH mRNA by pioglitazone, suggesting that PPARgamma activation is involved in the induction of PAF-AH by pioglitazone. As PAF promotes the cell motility with cytoskeletal reorganization, we investigated the effect of pioglitazone on PAF-mediated morphological changes in THP-1 macrophages. In the absence of pioglitazone, PAF promoted the elongation of actin cytoskeleton, which was inhibited by pretreatment with pioglitazone. In contrast, pioglitazone was not able to inhibit the morphological changes induced by C-PAF, a non-hydrolyzable PAF agonist. Thus, it is suggested that PAF-induced morphological changes could be inhibited by pioglitazone through PAF-AH, which rapidly hydrolyzed PAF. These data propose that PPARgamma/PAF-AH pathway is a clinical target for the prevention against atherosclerosis.
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1-Alquil-2-acetilglicerofosfocolina Esterasa/biosíntesis , Citoesqueleto/metabolismo , Macrófagos/efectos de los fármacos , Factor de Activación Plaquetaria/antagonistas & inhibidores , Tiazolidinedionas/farmacología , 1-Alquil-2-acetilglicerofosfocolina Esterasa/genética , 1-Alquil-2-acetilglicerofosfocolina Esterasa/fisiología , Línea Celular , Dinoprost/fisiología , Inducción Enzimática , Humanos , Macrófagos/enzimología , Macrófagos/metabolismo , Pioglitazona , Receptores Citoplasmáticos y Nucleares/fisiología , Factores de Transcripción/fisiologíaRESUMEN
Hyperhomocysteinemia has been reported to be an independent risk factor for atherosclerosis and atherothrombosis. However, the molecular mechanism by which hyperhomocysteinemia can lead to atherosclerosis and atherothrombosis has not been completely described. Vascular endothelial growth factor (VEGF) has been proposed to play an important role in the progression of atherosclerosis. In the present study, we hypothesized that hyperhomocysteinemia might be associated with VEGF expression in atherosclerotic lesions. We investigated VEGF mRNA expression and VEGF secretion by homocysteine (Hcy) in differentiated THP-1 macrophages. As a result, it has been revealed that VEGF mRNA was upregulated by Hcy in a dose- and time-dependent manner in THP-1 macrophages with the increase in VEGF secretion. Importantly, other sulfur compounds, such as methionine and cysteine, showed no effect on VEGF expression, indicating that homocysteine specifically induced VEGF. Our findings suggest that hyperhomocysteinemia could promote the development of atherosclerotic lesions through VEGF induction in macrophages.