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Black auroras are small-scale features embedded in the diffuse background aurora, typically occurring post-substorm after magnetic midnight and with an eastward drift imposed. Black auroras show a significant reduction in optical brightness compared to the surrounding diffuse aurora, and can appear as slow-moving arcs or rapidly-moving patches and arc segments. We report, for the first time, an even more elusive small-scale optical structure that has always been observed occurring paired with [Formula: see text] 10% of black aurora patches. A patch or arc segment of enhanced luminosity, distinctly brighter than the diffuse background, which we name the anti-black aurora, may appear adjacent to the black aurora. The anti-black aurora is of similar shape and size, and always moves in parallel to the drifting black aurora, although it may suddenly switch sides for no apparent reason. The paired phenomenon always drifts with the same average speed in an easterly direction. From the first dual-wavelength (427.8 nm and 844.6 nm) optical observations of the phenomenon recorded on 12 March 2016 outside Tromsø Norway, we show that the anti-black and black auroras have a higher and lower mean energy, respectively, of the precipitating electrons compared to the diffuse background.
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Vanadium is a metal whose toxicity towards terrestrial and aquatic species has been under-reported to date.. The biochemical responses of vanadium in amphibian species have not been determined. To establish the effects of vanadium (V) on exposed adult Xenopus laevis, acute and chronic exposures were conducted, and biomarker analyses were performed on liver and muscle tissues from exposed frogs. Biomarkers of exposure, such as acetylcholinesterase (AChE) and metallothioneins (MT), were analysed. Biomarkers of effect were also analysed to determine possible increases in reactive oxygen species (ROS), and the effect of the exposure on the energy balance in the organisms. These included superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), protein carbonyls (PC), malondialdehyde (MDA), and cellular energy allocation (CEA) (energy available, energy consumption, lipids, proteins and glucose). In acute exposures, the energy balances in organisms were distinctly affected, possibly due to insulin mimetic properties of V. In chronic exposures, MT, AChE, SOD, CAT and GSH responses were more pronounced. Although AChE is generally inhibited by pollutant exposure, in this study, it was stimulated. There were significant inhibitions of SOD and CAT, previously observed in frog species. PC levels increased in the highest acute exposure concentration, indicating protein damage. The IBR.v2 revealed the biochemical responses of V more effectively than traditional statistical analysis.
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Anfibios/fisiología , Antioxidantes/metabolismo , Contaminantes Químicos del Agua/toxicidad , Animales , Biomarcadores/metabolismo , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Malondialdehído/metabolismo , Metalotioneína/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Depression wetlands (colloquially referred to in South Africa (SA) as pans) are found worldwide and primarily occur in arid regions including North and South America, southern and central Africa and southern and western Australia. Surface water resources in SA, and specifically in Gauteng, are under pressure from urbanisation, poor agricultural practices and untreated mining and industrial effluent. Research of these wetlands will benefit the development of health assessment tools for these unique aquatic resources. The aim of this project was to determine the water quality and macroinvertebrate community structure for each perennial pan during consecutive dry and wet seasons and to establish a possible comparison between these pans that can be used as a baseline for future research on pans. The sampled pans in Gauteng presented higher TDS, Cl and Mg results compared to other South African studies, and similar SO4 results to pans in the Mpumalanga province. Ammonia, Al and Zn results of all pans through all sampling events exceed the Target Water Quality Range (TWQR) for aquatic ecosystems of the Water Quality Guidelines (WQG) from the Department of Water and Sanitation (DWS). The water quality from selected systems is suitable for livestock watering based on the DWS TWQR. Macroinvertebrate species of all sampled pans were mostly low water quality tolerant species with a predator dominant community structure. Seasonal variation of species was evident. Macroinvertebrate families found in the wet season include Hydrophilidae, Aeshnidae, Pleiidae, Ephemeroptera, Belostomatidae and Notonectidae. Families found in the dry season include Planaridae, Dysticidae, Hirudinidae and Daphnidae. Graphical representation of ordination analyses with Canoco version 5 (Ter Braak and Smilauer 2012) indicated that TDS, temperature, pH, sulphates and hardness are strong drivers of the existing macroinvertebrate community in most of the pans.
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Monitoreo del Ambiente/métodos , Calidad del Agua , Humedales , Agricultura , Animales , Ecosistema , Invertebrados , Minería , Estaciones del Año , Sudáfrica , UrbanizaciónRESUMEN
Eodromyia pumilio gen. et sp. nov., is described as the oldest record of the hybotid tribe Drapetini, from the Lowermost Eocene amber of Oise (France). It differs from described extant genera in the tribe, among other characters, by the complete absence of crossvein bm-cu.
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Dípteros , Fósiles , Ámbar , Animales , FranciaRESUMEN
Rapid detection of disease biomarkers at the patient point-of-care is essential to timely and effective treatment. The research described herein focuses on the development of an electrochemical surface-enhanced Raman spectroscopy (EC-SERS) DNA aptasensor capable of direct detection of tuberculosis (TB) DNA. Specifically, a plausible DNA biomarker present in TB patient urine was chosen as the model target for detection. Cost-effective screen printed electrodes (SPEs) modified with silver nanoparticles (AgNP) were used as the aptasensor platform, onto which the aptamer specific for the target DNA was immobilized. Direct detection of the target DNA was demonstrated through the appearance of SERS peaks characteristic for adenine, present only in the target strand. Modulation of the applied potential allowed for a sizeable increase in the observed SERS response and the use of thiol back-filling prevented non-specific adsorption of non-target DNA. To our knowledge, this work represents the first EC-SERS study of an aptasensor for the direct, label-free detection of DNA hybridization. Such a technology paves the way for rapid detection of disease biomarkers at the patient point-of-care.
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Aptámeros de Nucleótidos/química , ADN Bacteriano/análisis , Técnicas Electroquímicas , Espectrometría Raman , Electrodos , Humanos , Nanopartículas del Metal/química , Mycobacterium/genética , Hibridación de Ácido Nucleico , Plata/química , Tuberculosis/diagnósticoRESUMEN
A fundamental goal in nano-toxicology is that of identifying particle physical and chemical properties, which are likely to explain biological hazard. The first line of screening for potentially adverse outcomes often consists of exposure escalation experiments, involving the exposure of micro-organisms or cell lines to a library of nanomaterials. We discuss a modeling strategy, that relates the outcome of an exposure escalation experiment to nanoparticle properties. Our approach makes use of a hierarchical decision process, where we jointly identify particles that initiate adverse biological outcomes and explain the probability of this event in terms of the particle physicochemical descriptors. The proposed inferential framework results in summaries that are easily interpretable as simple probability statements. We present the application of the proposed method to a data set on 24 metal oxides nanoparticles, characterized in relation to their electrical, crystal and dissolution properties.
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Nanotechnology introduces a new field that requires novel approaches and methods for hazard and risk assessment. For an appropriate scientific platform for safety assessment, nanoscale properties and functions of engineered nanomaterials (ENMs), including how the physicochemical properties of the materials relate to mechanisms of injury at the nano-bio interface, must be considered. Moreover, this rapidly advancing new field requires novel test strategies that allow multiple toxicants to be screened in robust, mechanism-based assays in which the bulk of the investigation can be carried out at the cellular and biomolecular level whilst maintaining limited animal use and is based on the contribution of toxicological pathways to the pathophysiology of disease. First, a predictive toxicological approach for the safety assessment of ENMs will be discussed against the background of a '21st-century vision' for using alternative test strategies (ATSs) to perform toxicological assessment of large numbers of untested chemicals, thereby reducing a backlog that could otherwise become a problem for nanotechnology. An ATS is defined here as an alternative to animal experiments or refinement/reduction alternative to traditional animal testing. Secondly, the approach of selecting pathways of toxicity to screen for the pulmonary hazard potential of carbon nanotubes and metal oxides will be discussed, as well as how to use these pathways to perform high-content or high-throughput testing and how the data can be used for hazard ranking, risk assessment, regulatory decision-making and 'safer-by-design' strategies. Finally, the utility and disadvantages of this predictive toxicological approach to ENM safety assessment, and how it can assist the 21st-century vision, will be addressed.
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Ensayo de Materiales , Nanoestructuras , Nanotecnología , Seguridad , Animales , Humanos , Medición de RiesgoRESUMEN
In sub-Saharan Africa, HIV incidence and prevalence remain disproportionately high among women. Vaginal rings (VRs) have been formulated for the delivery of antiretroviral-based microbicides, and their favorable safety and tolerability profiles reported in clinical studies. Although the concept of drug release through a VR has existed since 1970, and VRs have been marketed since 1992 for contraceptive or hormone replacement purposes, VR use as a microbicide delivery system is a novel application. This is the first study to evaluate VR adherence among African women in the context of its potential use as an HIV prevention method, to examine predictors of adherence, and to describe clinical or contextual reasons for VR removals or nonadherence. This was a randomized trial of the safety and acceptability of a placebo VR worn for 12 weeks in 170 HIV-negative, African women aged 18-35 in four clinic sites in South Africa and Tanzania. The findings suggest that adherence to VR use in the context of HIV prevention trials in these communities should be high, thereby enabling more accurate assessment of an active microbicide safety and efficacy.
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Antiinfecciosos Locales/administración & dosificación , Dispositivos Anticonceptivos Femeninos/estadística & datos numéricos , Infecciones por VIH/prevención & control , Cumplimiento de la Medicación/estadística & datos numéricos , Administración Intravaginal , Adolescente , Adulto , Antiinfecciosos Locales/efectos adversos , Estudios Cruzados , Femenino , Humanos , Cumplimiento de la Medicación/etnología , Cumplimiento de la Medicación/psicología , Análisis Multivariante , Investigación Cualitativa , Factores Socioeconómicos , Sudáfrica , Tanzanía , Adulto JovenRESUMEN
Vaginal rings (VRs) are new methods for continuous delivery of microbicides. This is the first study to quantitatively and qualitatively explore the acceptability of rings in Africa: 157 HIV-negative, sexually active women aged 18-35 used a placebo silicone elastomer ring for 12 weeks. They completed product acceptability questionnaires every 4 weeks. We conducted 6 exit focus group discussions with a subset of 48 women and 19 in-depth interviews with male partners. Retention in the study was high (97 %). Initial insertion at the clinic was successful on first attempt for 81 % of participants. Most women were comfortable using the ring, and very few (≤2 %) could feel it during daily activities or had ring-related physical or emotional problems. In the qualitative interviews many participants reported that they initially had concerns about using the ring. However, only a minority of women actually reported concerns with the ring during the study. The most frequent concern was that the ring would get lost inside the body (20 %), and this was significantly correlated with study site, frequently thinking about the ring and reporting that the ring was not very easy to remove. Qualitative data suggest that informants grew to like the ring because it felt securely placed, was unnoticeable during daily activities, and felt "normal" during sex. The ring appeared to be highly acceptable for women and men. Initial concerns with this novel method suggest a need for enhanced product counseling when VRs are introduced.
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Antiinfecciosos/administración & dosificación , Dispositivos Anticonceptivos Femeninos/estadística & datos numéricos , Infecciones por VIH/prevención & control , Aceptación de la Atención de Salud/estadística & datos numéricos , Administración Intravaginal , Población Negra/psicología , Estudios Cruzados , Femenino , Grupos Focales , Humanos , Entrevistas como Asunto , Análisis Multivariante , Satisfacción del Paciente , Investigación Cualitativa , Conducta Sexual , Parejas Sexuales/psicología , Factores Socioeconómicos , Sudáfrica , Encuestas y Cuestionarios , TanzaníaRESUMEN
Nesterenkonia strain AN1 was isolated from a screening program for nitrile- and amide-hydrolyzing microorganisms in Antarctic desert soil samples. Strain AN1 showed significant 16S rRNA sequence identity to known members of the genus. Like known Nesterenkonia species, strain AN1 was obligately alkaliphilic (optimum environmental pH, 9 to 10) and halotolerant (optimum environmental Na(+) content, 0 to 15% [wt/vol]) but was also shown to be an obligate psychrophile with optimum growth at approximately 21°C. The partially sequenced genome of AN1 revealed an open reading frame (ORF) encoding a putative protein member of the nitrilase superfamily, referred to as NitN (264 amino acids). The protein crystallized readily as a dimer and the atomic structure of all but 10 amino acids of the protein was determined, confirming that the enzyme had an active site and a fold characteristic of the nitrilase superfamily. The protein was screened for activity against a variety of nitrile, carbamoyl, and amide substrates and was found to have only amidase activity. It had highest affinity for propionamide but demonstrated a low catalytic rate. NitN had maximal activity at 30°C and between pH 6.5 and 7.5, conditions which are outside the optimum growth range for the organism.
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Amidohidrolasas/química , Amidohidrolasas/metabolismo , Ácidos Grasos/metabolismo , Micrococcaceae/enzimología , Amidohidrolasas/genética , Secuencia de Aminoácidos , Regiones Antárticas , Dominio Catalítico , Análisis por Conglomerados , Cristalografía por Rayos X , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Estabilidad de Enzimas , Concentración de Iones de Hidrógeno , Micrococcaceae/crecimiento & desarrollo , Micrococcaceae/aislamiento & purificación , Modelos Moleculares , Datos de Secuencia Molecular , Filogenia , Multimerización de Proteína , Estructura Cuaternaria de Proteína , ARN Ribosómico 16S/genética , Alineación de Secuencia , Análisis de Secuencia de ADN , Cloruro de Sodio/metabolismo , Microbiología del Suelo , Especificidad por Sustrato , TemperaturaRESUMEN
Nanomaterials hold great promise for medical, technological and economical benefits. Knowledge concerning the toxicological properties of these novel materials is typically lacking. At the same time, it is becoming evident that some nanomaterials could have a toxic potential in humans and the environment. Animal based systems lack the needed capacity to cope with the abundance of novel nanomaterials being produced, and thus we have to employ in vitro methods with high throughput to manage the rush logistically and use high content readouts wherever needed in order to gain more depth of information. Towards this end, high throughput screening (HTS) and high content screening (HCS) approaches can be used to speed up the safety analysis on a scale that commensurate with the rate of expansion of new materials and new properties. The insights gained from HTS/HCS should aid in our understanding of the tenets of nanomaterial hazard at biological level as well as assist the development of safe-by-design approaches. This review aims to provide a comprehensive introduction to the HTS/HCS methodology employed for safety assessment of engineered nanomaterials (ENMs), including data analysis and prediction of potentially hazardous material properties. Given the current pace of nanomaterial development, HTS/HCS is a potentially effective means of keeping up with the rapid progress in this field--we have literally no time to lose.
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Bioensayo/métodos , Bioensayo/tendencias , Nanoestructuras/toxicidad , Nanotecnología/métodos , Nanotecnología/tendencias , Pruebas de Toxicidad/métodos , Pruebas de Toxicidad/tendencias , Femenino , Humanos , MasculinoRESUMEN
In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS effects in apolipoprotein E knockout (ApoE-/-) mice exposed to two levels of concentrated ultrafine particulate matter in central Los Angeles. Mice were euthanized 24h after the last exposure and brain, liver, heart, lung and spleen tissues were collected and frozen for subsequent bioassays. There was clear evidence of aberrant immune activation in the brains of exposed animals as judged by a dose-related increase in nuclear translocation of two key transcription factors, NF-kappaB and AP-1. These factors are involved in the promotion of inflammation. Increased levels of glial fibrillary acidic protein (GFAP) were also found consequent to particulate inhalation suggesting that glial activation was taking place. In order to determine the mechanism by which these events occurred, levels of several MAP kinases involved in activation of these transcription factors were assayed by Western blotting. There were no significant changes in the proportion of active (phosphorylated) forms of ERK-1, IkB and p38. However, the fraction of JNK in the active form was significantly increased in animals receiving the lower concentration of concentrated ambient particles (CAPs). This suggests that the signaling pathway by which these transcription factors are activated involves the activation of JNK.
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Enfermedades del Sistema Nervioso Central/inducido químicamente , Enfermedades del Sistema Nervioso Central/patología , Proteínas Quinasas Activadas por Mitógenos/fisiología , Material Particulado/toxicidad , Transducción de Señal/efectos de los fármacos , Animales , Apolipoproteínas E/genética , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Enfermedades del Sistema Nervioso Central/enzimología , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Proteína Ácida Fibrilar de la Glía/metabolismo , Inflamación/enzimología , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/fisiología , Neuroglía/metabolismo , Neuroglía/patología , Estrés Oxidativo/efectos de los fármacos , Tamaño de la Partícula , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factor de Transcripción AP-1/metabolismoAsunto(s)
Apoptosis/fisiología , Carbono , Daño del ADN , Células Epiteliales/fisiología , Neumonía/fisiopatología , Mucosa Respiratoria/fisiopatología , Emisiones de Vehículos/toxicidad , Animales , Recuento de Células , Ciclina E/metabolismo , Quinasa 2 Dependiente de la Ciclina/metabolismo , Humanos , Estrés Oxidativo/fisiología , Tamaño de la Partícula , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The underlying pathophysiological basis of tardive dyskinesia (TD) remains speculative. Haloperidol (HP) inhibits neuronal nitric oxide (NO) synthase (NOS) activity in vitro, but has not to date been studied in an intact animal model. Recent animal studies have found that extrapyramidal dysfunction evoked by chronic HP is associated with suppression of striatal cyclic guanosine monophosphate (cGMP), as well as plasma nitrogen oxides. Striatal dopamine (DA) is central to motor control, while NO plays an important neuroregulatory role in striatal DA function. Recent case reports suggest that atypical antipsychotics, such as olanzapine (OLZ), may be effective in reversing TD. Here, rats treated with HP (1.5 mg/kg per day p.o.) for 28 days developed significant vacuous chewing movements (VCMs) together with significant suppression of striatal NOS activity. Acute challenge with OLZ (1 and 2 mg/kg i.p.) significantly reversed both HP-induced VCMs and suppression of striatal NOS activity. Therefore TD may involve attenuation of NO-mediated neuromodulation in the striatum. Reversal of VCMs and NOS suppression with OLZ suggests that disinhibition of striatal NOS activity may underlie the clinical benefit of OLZ in TD.
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Antipsicóticos/efectos adversos , Cuerpo Estriado/metabolismo , Discinesia Inducida por Medicamentos/metabolismo , Haloperidol/efectos adversos , Óxido Nítrico Sintasa/metabolismo , Pirenzepina/análogos & derivados , Pirenzepina/efectos adversos , Animales , Benzodiazepinas , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/enzimología , GMP Cíclico/metabolismo , Discinesia Inducida por Medicamentos/psicología , Masculino , Masticación , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Olanzapina , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of this study was to establish and validate a method to permit microsatellite analysis of DNA profiles obtained from frozen-thawed stallion sperm cells. This would provide reliable and accurate verification of the identification of a semen donor. Ejaculates from 5 pony stallions were collected, processed and frozen in 0.5 ml plastic straws. Aliquots of 100 microl of the frozen-thawed semen thus obtained were either placed directly, or diluted (1:10; 1:100; and 1:1000) and placed on slides of FTA paper. Similarly, blood samples obtained from each of the stallions were placed onto slides of FTA paper. A punch was removed from each sample after drying Each sample was mixed with FTA purification reagent, Dithiothreitol and Proteinase K before incubation and processing. All samples were processed with a set of 13 microsatellite markers. Further analysis permitted a comparison of the DNA profiles of the frozen-thawed semen and the blood samples. A full profile of markers was obtained from the 1:10 and 1:100 dilutions of the frozen-thawed semen samples as well as from the blood samples. The DNA profiles from the frozen-thawed semen and blood samples obtained from the stallions matched in all cases.
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Criopreservación/veterinaria , ADN/análisis , Caballos/genética , Repeticiones de Microsatélite , Preservación de Semen/veterinaria , Espermatozoides/química , Animales , MasculinoRESUMEN
Menadione (vitamin K3) a redox cycling quinone, is a clinically important chemotherapeutic agent. The objective of this study was to clarify the cytotoxic mechanisms by which menadione induces cell death in a lymphoblastoid cell line. Our results show that while the Jun kinase cascade and FasL expression may contribute to cell death at lower drug concentrations, a mitochondrial pathway dominates the cytotoxic effect at higher menadione concentrations. Menadione treatment clearly affected the mitochondrial function of Jurkat T cells by inducing a collapse of the inner transmembrane potential (DeltaPsi(m)) and a decrease in inner membrane mass, which could be completely reversed by N-acetylcysteine. Importantly, while a broad range of fmk-derived caspase inhibitors had potent effects on Fas-induced apoptosis, they failed to interfere in menadione cytotoxicity, indicating that menadione-induced cell death is predominantly Fas-independent. In addition, the mitochondrial changes coincided with ATP depletion. The failure in ATP production explains the occurrence of Fas-independent death events.
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Antifibrinolíticos/toxicidad , Apoptosis/inmunología , Estrés Oxidativo/inmunología , Linfocitos T/inmunología , Linfocitos T/patología , Vitamina K 3/toxicidad , Receptor fas/inmunología , Apoptosis/efectos de los fármacos , Proteína Ligando Fas , Humanos , Células Jurkat , Glicoproteínas de Membrana/inmunología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Transducción de Señal , Linfocitos T/metabolismoRESUMEN
We review the literature indicating that the adverse health effects of ambient particulate matter involve the generation of oxidative stress and inflammation, as well as immunomodulating effects by particle-associated chemicals. We discuss evidence that diesel exhaust particle organic extracts induce reactive oxygen species in macrophages and bronchial epithelial cells, two key cell types targeted by particulate matter in the lung. Reactive oxygen species activate the promoters of cytokines and chemokines involved in allergic inflammation through activator protein-1 and nuclear factor- kappaB signaling pathways, which may explain exacerbation of allergic inflammation. Organic diesel exhaust particle chemicals also induce apoptosis and necrosis in bronchial epithelial cells via a mitochondrial pathway. This may be responsible for epithelial shedding and bronchial hyperreactivity in asthma.
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Asma/etiología , Contaminantes Ambientales/efectos adversos , Compuestos Orgánicos/efectos adversos , Estrés Oxidativo , Neumonía/etiología , Neumonía/fisiopatología , Hidrocarburos Policíclicos Aromáticos/efectos adversos , Asma/fisiopatología , Monitoreo del Ambiente , Femenino , Humanos , Masculino , Tamaño de la Partícula , Pronóstico , Medición de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
We investigated the role of protein kinase C theta (PKCtheta) in the activation of the NF-kappaB cascade in primary human CD4(+) lymphocytes. Among six or so PKC isoforms expressed in T cells, only PKCtheta participates in the assembly of the supramolecular activation clusters at the contact site of the TCR with Ag. Signaling via both the TCR and CD28 is required for optimal activation of the multisubunit IkappaB kinase (IKK) complex in primary human T lymphocytes; this activation could be inhibited by a Ca(2+)-independent PKC isoform inhibitor, rottlerin. Moreover, endogenous PKCtheta physically associates with activated IKK complexes in CD3/CD28-costimulated primary CD4(+) T cells. The same set of stimuli also induced relocation of endogenous PKCtheta and IKKs to a GM1 ganglioside-enriched, detergent-insoluble membrane compartment in primary T cells. IKKs recruited to these lipid rafts were capable of phosphorylating a recombinant IkappaBalpha sustrate. Confocal microscopy further demonstrated that exogenously expressed PKCtheta and IKKss colocalize in the membrane of CD3/CD28-costimulated Jurkat T cells. Constitutively active but not kinase-inactive PKCtheta activated IKKbeta in Jurkat T cells. Expression of dominant-active PKCtheta also had stimulatory effects on the CD28 response element of the IL-2 promoter. Taken together, these data show that the activation of PKCtheta by the TCR and CD28 plays an important role in the assembly and activation of IKK complexes in the T cell membrane.
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Antígenos CD28/fisiología , Inhibidores Enzimáticos/metabolismo , Isoenzimas/fisiología , Microdominios de Membrana/enzimología , FN-kappa B/metabolismo , Proteína Quinasa C/fisiología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T/fisiología , Transducción de Señal/inmunología , Antígenos CD28/genética , Antígenos CD28/metabolismo , Complejo CD3/fisiología , Linfocitos T CD4-Positivos/enzimología , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Activación Enzimática/inmunología , Regulación de la Expresión Génica/inmunología , Humanos , Quinasa I-kappa B , Isoenzimas/biosíntesis , Isoenzimas/metabolismo , Células Jurkat/enzimología , Células Jurkat/metabolismo , Microdominios de Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Regiones Promotoras Genéticas/inmunología , Proteína Quinasa C/biosíntesis , Proteína Quinasa C/metabolismo , Proteína Quinasa C-theta , Proteínas Serina-Treonina Quinasas/metabolismo , Elementos de Respuesta/inmunología , Talina/metabolismoRESUMEN
Diesel exhaust particles (DEP) enhance allergic inflammation by increasing in vivo IgE and cytokine production in the human upper respiratory mucosa. CC chemokines have been shown to play an important role in inflammation. We examined whether DEP could alter the production of CC chemokines by cells residing in the human nasal mucosa. At both 6 and 24 h following intranasal DEP challenge, the levels of nasal RANTES, MIP-1alpha, and MCP-3 were significantly elevated compared to baseline. In contrast, DEP did not enhance levels of Eotaxin at any time, demonstrating that the action of DEP was not simply a global effect on all CC chemokines. Challenge with saline resulted in no significant change in expression of any chemokine at any time. Challenge with DEP also resulted in an increase in total cell counts in nasal lavage fluids. Increases in lymphocyte, monocyte/macrophage, and neutrophil cells were observed but there was no change in eosinophil cell numbers. In contrast, there was a significant enhancement of ECP protein levels in washes performed 6 to 24 h after DEP challenge. Elevated specific nasal chemokine expression following exposure to DEP likely participates in the inflammation, cellular infiltration, and increase in IgE observed in the absence of allergen.