RESUMO
Planetary rings are observed not only around giant planets1, but also around small bodies such as the Centaur Chariklo2 and the dwarf planet Haumea3. Up to now, all known dense rings were located close enough to their parent bodies, being inside the Roche limit, where tidal forces prevent material with reasonable densities from aggregating into a satellite. Here we report observations of an inhomogeneous ring around the trans-Neptunian body (50000) Quaoar. This trans-Neptunian object has an estimated radius4 of 555 km and possesses a roughly 80-km satellite5 (Weywot) that orbits at 24 Quaoar radii6,7. The detected ring orbits at 7.4 radii from the central body, which is well outside Quaoar's classical Roche limit, thus indicating that this limit does not always determine where ring material can survive. Our local collisional simulations show that elastic collisions, based on laboratory experiments8, can maintain a ring far away from the body. Moreover, Quaoar's ring orbits close to the 1/3 spin-orbit resonance9 with Quaoar, a property shared by Chariklo's2,10,11 and Haumea's3 rings, suggesting that this resonance plays a key role in ring confinement for small bodies.
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PURPOSE: Simultaneous pancreas-kidney transplantation (SPKT) remains the best treatment option in patients with type 1 diabetes and chronic kidney failure. There are only a few studies addressing the potential ischemic deterioration of peripheral arterial disease (PAD) due to blood diverting from the iliac artery to the kidney graft. We aimed to evaluate diabetic foot lesions and PAD evolution in SPKT recipients and investigate if they are more frequent in ipsilateral lower limb of kidney graft. METHODS: We developed a retrospective cohort, including patients submitted to SPKT in our tertiary center, between 2000 and 2017. Diabetic foot lesions and PAD frequencies were compared in the period before and after transplantation. RESULTS: Two hundred and eleven patients were included, 50.2% (n = 106) female, with a median age at transplantation of 35 years (IQR 9). After a median follow-up period of 10 years (IQR 7), patient, kidney, and pancreatic graft survival were 90.5% (n = 191), 83.4% (n = 176), and 74.9% (n = 158), respectively. Before transplant, 2.8% (n = 6) had PAD and 5.3% (n = 11) had history of foot lesions. In post-transplant period, 17.1% (n = 36) patients presented PAD and 25.6% (n = 54) developed diabetic foot ulcers, 47.6% (n = 35) of which in the ipsilateral and 53.3% (n = 40) in the contralateral lower limb of the kidney graft (p = 0.48). Nine patients (4.3%) underwent major lower limb amputation, 3 (30%) ipsilateral and 7 (70%) contralateral to the kidney graft (p = 0.29). CONCLUSIONS: Diabetic foot lesions were not more frequent in the ipsilateral lower limb of the kidney graft, therefore downgrading the 'steal syndrome' role in these patients.
Assuntos
Diabetes Mellitus Tipo 1 , Pé Diabético , Transplante de Rim , Doença Arterial Periférica , Humanos , Feminino , Criança , Pé Diabético/etiologia , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Doença Arterial Periférica/etiologia , Pâncreas , Resultado do TratamentoRESUMO
Natural mineral waters (NMWs) emerge from the earth as springs and their beneficial therapeutic effect has been empirically recognized in different countries. Portugal has diverse NMW resources that are sought for the relief of different afflictions including dermatological complications. However, there is a lack of scientific validation supporting this empiric knowledge. In this study, we aimed to screen the in vitro bioactivity of Portuguese NMWs with different chemical profiles, namely sulfurous/bicarbonate/sodic (SBS), bicarbonate/magnesium, sulfated/calcic, sulfurous/chlorinated/sodic, sulfurous/bicarbonate/fluoridated/sodic, and chlorinated/sodic, focusing on aging-related skin alterations. Mouse skin fibroblasts and macrophages were exposed to culture medium prepared in different NMWs. Cellular viability was evaluated by MTT assay and etoposide-induced senescence was analyzed through the beta-galactosidase staining kit. Wound healing was investigated by the scratch assay, and phototoxicity/photoprotection after UVA irradiation was evaluated using a neutral red solution. ROS production was quantified using the 2'7'-dichlorofluorescin diacetate dye, and the activity of superoxide dismutase (SOD) was analyzed by a commercial kit after lipopolysaccharide exposure. NMWs within the SBS profile demonstrated anti-senescence activity in skin fibroblasts, along with a variable effect on cellular viability. Among the tested NMWs, two decreased cellular senescence and preserved cell viability and were therefore selected for subsequent studies, together with a SBS NMW with therapeutic indications for dermatologic diseases. Overall, the selected NMW promoted wound healing in skin fibroblasts and activated SOD in macrophages, thus suggesting an anti-oxidant effect. None of the NMWs prevented phototoxicity after UV irradiation. Our results shed a light on the anti-aging potential of Portuguese NMW, supporting their putative application in cosmetic or medical products.
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Águas Minerais , Envelhecimento da Pele , Animais , Antioxidantes/farmacologia , Bicarbonatos , Células Cultivadas , Etoposídeo/farmacologia , Lipopolissacarídeos/farmacologia , Magnésio , Camundongos , Vermelho Neutro/farmacologia , Portugal , Espécies Reativas de Oxigênio , Pele , Superóxido Dismutase , Raios Ultravioleta , beta-Galactosidase/farmacologiaRESUMO
Optosensing chitosan-based membranes have been applied for the detection of heavy metals, especially in drinking water. The novelty of this study is based on the use of sulphated polysaccharides, in such optosensing membranes, aiming at an improved analytical performance. The sulphated polysaccharides, such as ulvan, fucoidan and chondroitin sulfate, were extracted from by-products and wastes of marine-related activities. The membranes were developed for the analysis of aluminum. The variation in the visible absorbance of the sensor membranes after the contact between the chromophore and the aluminum cation was studied. The membranes containing sulphated polysaccharides showed improved signals when compared to the chitosan-only membrane. As for the detection limits for the membranes containing ulvan, fucoidan and chondroitin sulfate, 0.17 mg L-1, 0.21 mg L-1 and 0.36 mg L-1 were obtained, respectively. The values were much lower than that obtained for the chitosan-only membrane, 0.52 mg L-1, which shows the improvement obtained from the sulphated polysaccharides. The results were obtained with the presence of CTAB in analysis solution, which forms a ternary complex with the aluminum cation and the chromophore. This resulted in an hyperchromic and batochromic shift in the absorption band. When in the presence of this surfactant, the membranes showed lower detection limits and higher selectivity.
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Quitosana , Sulfatos de Condroitina , Alumínio , Cátions , Polissacarídeos/análise , SulfatosRESUMO
Mesenchymal stem/stromal cells (MSCs) have been increasingly used in clinical trials for low-back pain (LBP) and intervertebral disc (IVD) degeneration with promising results. Their action mechanisms are not fully understood, but they reduce IVD pro-inflammatory markers in a pro-inflammatory/degenerative IVD microenvironment. In this study the therapeutic potential of the MSC secretome, as an alternative cell-free approach for treating degenerated IVDs, was examined. Human bone marrow-derived MSC secretome (MSCsec) was collected after 48 h of preconditioning in IL-1ß (10 ng/mL) and low oxygen (6 % O2), mimicking the degenerative IVD. IL-1ß-pre-conditioning of MSCs increased secretion of pro-inflammatory markers hIL-6, hIL-8, hMCP-1, etc. The therapeutic effect of MSCsec was tested in a pro-inflammatory/degenerative IVD ex vivo model. MSCsec down-regulated IVD gene expression of pro-inflammatory cytokines (bIL-6, bIL-8) and matrix degrading enzyme bMMP1, while bMMP3 and bTIMP2 were up-regulated, at 48 h. After 14 d, MSCsec-treated IVDs revealed increased aggrecan deposition, although no differences in other ECM components were observed. Protein analysis of the MSCsec-treated IVD supernatant revealed a significant increase of CXCL1, MCP-1, MIP-3α, IL-6, IL-8 and GRO α/ß/γ (related to TNF, NOD-like receptor and neutrophil chemotaxis signalling), and a decrease of IFN-γ, IL-10, IL-4, IL-5 and TNF-α (associated with T-cell receptor signalling). MSCsec-treated IVD supernatants did not promote angiogenesis and neurogenesis in vitro. Overall, MSCsec can be a safe therapeutic approach, presenting a strong immunomodulatory role in degenerated IVD while potentiating aggrecan deposition, which can open new perspectives on the use of MSCsec as a cell-based/ cell-free therapeutic approach to LBP.
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Agrecanas/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Disco Intervertebral/metabolismo , Células-Tronco Mesenquimais/metabolismo , Secretoma/metabolismo , Adolescente , Adulto , Animais , Bovinos , Células Cultivadas , Citocinas/metabolismo , Humanos , Degeneração do Disco Intervertebral/metabolismo , Pessoa de Meia-Idade , Adulto JovemRESUMO
The diagnostic accuracy of the I3M to assess the legal age of 18 years has already been tested in several specific-population samples. The left lower third molar has been extensively used for discriminating between minors and adults. This research aimed to compare the usefulness of lower third molar maturity indexes, from both left and right side (I3ML and I3MR), in samples originating from four distinct continents in order to examine possible differences in their accuracy values. For this purpose, a sample of 10,181 orthopantomograms (OPGs), from Europe, Africa, Asia and America, was analysed and previously scored in other studies. The samples included healthy subjects with no systemic disorders with both third molars and clear depicted root apices. Wilcoxon Signed Rank test for left and right asymmetry did not show any significant differences. Data about sensitivity, specificity, predictive values, likelihood ratio and accuracy were pooled together and showed similar results for I3ML and I3MR, respectively. In addition, all these quantities were high when only the I3MR was considered to discriminate between adults and minors. The present referable database was the first to pool third molar measurements using panoramic radiographs of subjects coming from different continents. The results highlighted that both I3ML and I3MR are reliable indicators for assessing the legal age of 18 years old in those jurisdictions where this legal threshold has been set as the age of majority.
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Determinação da Idade pelos Dentes/métodos , Dente Serotino/diagnóstico por imagem , Dente Serotino/crescimento & desenvolvimento , Grupos Raciais , Etnicidade , Feminino , Humanos , Masculino , Mandíbula/diagnóstico por imagem , Mandíbula/crescimento & desenvolvimento , Radiografia Panorâmica , Sensibilidade e EspecificidadeRESUMO
Since the last revision in 2015, the taxonomy of section Flavipedes evolved rapidly along with the availability of new species delimitation techniques. This study aims to re-evaluate the species boundaries of section Flavipedes members using modern delimitation methods applied to an extended set of strains (n = 90) collected from various environments. The analysis used DNA sequences of three house-keeping genes (benA, CaM, RPB2) and consisted of two steps: application of several single-locus (GMYC, bGMYC, PTP, bPTP) and multi-locus (STACEY) species delimitation methods to sort the isolates into putative species, which were subsequently validated using DELINEATE software that was applied for the first time in fungal taxonomy. As a result, four new species are introduced, i.e. A. alboluteus, A. alboviridis, A. inusitatus and A. lanuginosus, and A. capensis is synonymized with A. iizukae. Phenotypic analyses were performed for the new species and their relatives, and the results showed that the growth parameters at different temperatures and colonies characteristics were useful for differentiation of these taxa. The revised section harbors 18 species, most of them are known from soil. However, the most common species from the section are ecologically diverse, occurring in the indoor environment (six species), clinical samples (five species), food and feed (four species), droppings (four species) and other less common substrates/environments. Due to the occurrence of section Flavipedes species in the clinical material/hospital environment, we also evaluated the susceptibility of 67 strains to six antifungals (amphotericin B, itraconazole, posaconazole, voriconazole, isavuconazole, terbinafine) using the reference EUCAST method. These results showed some potentially clinically relevant differences in susceptibility between species. For example, MICs higher than those observed for A. fumigatus wild-type were found for both triazoles and amphotericin B for A. ardalensis, A. iizukae, and A. spelaeus whereas A. lanuginosus, A. luppiae, A. movilensis, A. neoflavipes, A. olivimuriae and A. suttoniae were comparable to or more susceptible as A. fumigatus. Finally, terbinafine was in vitro active against all species except A. alboviridis.
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1. Uniformity in animal products is an important aspect of the production system. Several studies have reported estimates of genetics on residual variance in different species, indicating that it could be exploited to improve uniformity by selection. Nevertheless, there are no reports about the possibilities of such a selection strategy in meat quail.2. Records of hatching weight (HW) and body weight at 42 days (W42) of female and male birds from two meat quail lines (UFV1 and UFV2) were analysed. A three-step genetic evaluation was used to investigate the effect of genetic variation on residual variance of HW and W42 in both lines. In Step 1, a single-trait model was fitted to the data. In Step 2, log-transformed squared estimated residuals (ln(ê2)) were evaluated for these traits. In Step 3, a multi-trait analysis was performed to estimate the genetic correlation between the additive genetic effects for HW, W42, and their respective ln(ê2).3. The heritability estimates ranged from 0.12 to 0.23 for HW and from 0.22 to 0.35 for W42. The estimated heritabilities for the residual part were low and ranged from 0.0003 to 0.02 for both traits, and the genetic coefficient of variation residual variance estimates ranged from 0.31 to 0.42 for HW and from 0.09 to 0.25 for W42. Genetic correlations between the means (HW and W42) and ln(ê2) values were both positive and did not differ from zero, indicating no association between mean and ln(ê2).4. In conclusion, the uniformity of HW and W42 could be improved by selecting for lower residual variance in both meat quail lines, but the accuracy of selection may be low due to low heritability for uniformity, mainly for W42.
Assuntos
Galinhas , Codorniz , Animais , Teorema de Bayes , Peso Corporal/genética , Coturnix/genética , Feminino , Masculino , Carne , Codorniz/genéticaRESUMO
More and more by-products are being used in certain materials, especially in the construction industry. Natural construction materials contain amounts of heavy metals and radionuclides, but when by-products are used in these kinds of materials, this could lead to a growth in their concentrations and have a negative impact on public health.In this paper, red mud was used as a raw material (as a clay substitute) to manufacture fired bricks. Physical, mechanical, radiological and heavy metal leaching properties of fired bricks with a replacement ratio of up to 80â¯wt% of clay to red mud are discussed. In addition, the effect of different sintering temperatures (1173K and 1373K) was analyzed, and results showed that the higher the temperature produced, the higher the mechanical strength.To environmentally characterize materials, they were subjected to two different leaching tests: a batch test for raw materials and a monolithic test for the bricks, respectively. The results obtained were compared with the limits stated for several heavy metals by the European Landfill Directive. Results showed that red mud gives leachate concentration values for Cr higher than the limits stated for non-hazardous by-products. Bricks do not exhibit the same problem in the samples containing a high RM proportion and manufactured at a low sintering temperature (1173K), although in the case of V, a high concentration is observed.The contents of radionuclides such as Ra-220, Th-232 and K-40 of the final construction materials were analyzed and compared with different indexes. This paper indicates the maximum amounts of RM that can be used to replace clay for the manufacture of fired bricks without environmental risk.
Assuntos
Metais Pesados , Reciclagem , Silicatos de Alumínio , Argila , Materiais de Construção , Metais Pesados/análiseRESUMO
BACKGROUND: to understand if patients seen at Centro Hospitalar Psiquiátrico de Lisboa (CHPL) live in geographical clusters or randomly throughout the city, as well as determine their access to the psychiatric hospital and primary care facilities (PCF). METHODS: spatial autocorrelation statistics were performed (queen criterion of contiguity), regarding all patients observed at CHPL in 2017 (at the census subsection level), and considering not only their overall number but also main diagnosis, and admission to the psychiatric ward - voluntary or compulsory. Distance to the hospital and to the closest PCF was measured (for each patient and the variables cited above), and the mean values were compared. Finally, the total number of patients around each PCF was counted, considering specified radius sizes of 656 and 1000 m. RESULTS: All 5161 patients (509 psychiatric admissions) were geolocated, and statistical significance regarding patient clustering was found for the total number (p-0.0001) and specific group of disorders, namely Schizophrenia and related disorders (p-0.007) and depressive disorders (p-0.0002). Patients who were admitted in a psychiatric ward live farther away from the hospital (p-0.002), with the compulsory admissions (versus voluntary ones) living even farther (p-0.004). Furthermore, defining a radius of 1000 m for each PCF allowed the identification of two PCF with more than 1000 patients, and two others with more than 800. CONCLUSIONS: as patients seem to live in geographical clusters (and considering PCFs with the highest number of them), possible locations for the development of programs regarding mental health treatment and prevention can now be identified.
Assuntos
Serviços Comunitários de Saúde Mental , Acessibilidade aos Serviços de Saúde , Atenção Primária à Saúde , Adulto , Feminino , Hospitalização/estatística & dados numéricos , Hospitais Psiquiátricos/estatística & dados numéricos , Humanos , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Portugal/epidemiologia , Estudos Retrospectivos , Análise EspacialRESUMO
AIM: Steviol is a natural diterpenoid glycoside isolated from Stevia rebaudiana Bertoni leaves and widely used as a non-caloric sweetener. In addition to their sweet taste, Steviol glycosides may also have some therapeutic benefits. There are few reports on the cytotoxicity of Steviol in human cells. Our objective was to test this sweetener under and at average concentrations of consumption, evaluating parameters of cytotoxicity, genotoxicity, and immunotoxicity. METHODS: For this purpose, we made use of lymphocyte cultures and the analysis of their CD3+, CD4+, and CD8+ subpopulations. In a complementary way, the mechanism of action is proposed here by computational methods. RESULTS AND CONCLUSION: Our results showed that Steviol reduces the number of lymphocytes due to falls of CD4+, CD8+, and CD4+CD8+ subpopulations. Besides, we observed an increase in the level of DNA damage and a gradual incidence of structural changes in the lymphocyte chromosomal sets. It was possible to propose that Steviol modulates gene expression, mainly interfering with the SESN1, NAP1L1, SOX4, and TREX1 genes. Although Steviol is used globally as a sweetener, its use should be cautious, as our study points out that Steviol has cytotoxic, genotoxic and mutagenic effects in the concentrations and conditions tested in the culture of human lymphocyte cells.
Assuntos
Dano ao DNA , Diterpenos do Tipo Caurano/toxicidade , Subpopulações de Linfócitos/efeitos dos fármacos , Edulcorantes/toxicidade , Células Cultivadas , Relação Dose-Resposta a Droga , Exodesoxirribonucleases/genética , Exodesoxirribonucleases/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Subpopulações de Linfócitos/metabolismo , Subpopulações de Linfócitos/patologia , Proteína 1 de Modelagem do Nucleossomo/genética , Proteína 1 de Modelagem do Nucleossomo/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Medição de Risco , Fatores de Transcrição SOXC/genética , Fatores de Transcrição SOXC/metabolismo , Testes de ToxicidadeRESUMO
BACKGROUND: The aim was to examine the interval since first symptoms until final diagnosis of squamous cell carcinoma (SCC) in the head and neck region in southern Brazil. MATERIAL AND METHODS: The individuals were prospectively selected and underwent anamnesis, physical examination and interview in the first medical consultation at a Cancer Hospital from south of Brazil. RESULTS: From 488 patients who underwent clinical examination, 105 were included in the study with diagnosis of SCC. Patients average interval from first symptoms to final diagnosis was 152 days (median 86; max:1105; min: 1), the average professional interval was 108 days (median: 97; max:525; min: 1) , and the average total period interval was 258 days (median: 186; max:1177; min: 45). Factors statistically associated with patient and diagnosis itinerary intervals were smoking and poorly adapted dentures and distance from home to hospital, respectively. CONCLUSIONS: The identification of the itinerary characteristics of this specific population may reflect in more effective public policies, such as primary and secondary prevention programs, aiming to increase the survival of oncological patient. Furthermore, the knowledge of the variables that influence the late diagnosis minimizes patient's journey in search of care to cancer centers through health programs.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Brasil/epidemiologia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Pescoço , FumarRESUMO
Summary: Introduction. Sublingual immunotherapy (SLIT) with Pru p 3 can prevent severe allergic reactions to LTP-containing foods, but the standard initiation protocol is time-consuming. Objectives. Establish the safety of a novel ultra-rush initiation protocol for SLIT with Pru p 3. Methods. Prospective study comparing the side effects of the standard vs novel ultra-rush initiation protocols of SLIT with Pru p 3 in patients with anaphylaxis to LTP. Results. Fifteen patients were included (standard initiation, 5; ultra-rush initiation, 10), 80% females. All patients had oropharyngeal pruritus during initiation, 80% with spontaneous recovery, but no other gastro-intestinal, respiratory, cutaneous or systemic side effects occurred in any patient of both groups. Conclusion. The novel ultra-rush protocol halved the build-up time without increasing side effects.
Assuntos
Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Proteínas de Transporte/administração & dosagem , Hipersensibilidade Alimentar/terapia , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/imunologia , Imunoterapia Sublingual/métodos , Adolescente , Adulto , Anafilaxia/imunologia , Anafilaxia/patologia , Proteínas de Transporte/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Masculino , Estudos Prospectivos , Prunus persica/imunologia , Prurido/terapia , Estudos Retrospectivos , Imunoterapia Sublingual/efeitos adversos , Adulto JovemRESUMO
A sensing configuration for the real-time monitoring, detection, and quantification of dissolved carbon dioxide (dCO2) was developed for aquaculture and other applications in freshwater and saline water. A chemical sensing membrane, based on a colorimetric indicator, is combined with multimode optical fiber and a dual wavelength light-emitting diode (LED) to measure the dCO2-induced absorbance changes in a self-referenced ratiometric scheme. The detection and processing were achieved with an embeded solution having a mini spectrometer and microcontroller. For optrode calibration, chemical standard solutions using sodium carbonate in acid media were used. Preliminary results in a laboratory environment showed sensitivity for small added amounts of CO2 (0.25 mg·L-1). Accuracy and response time were not affected by the type of solution, while precision was affected by salinity. Calibration in freshwater showed a limit of detection (LOD) and a limit of quantification (LOQ) of 1.23 and 1.87 mg·L-1, respectively. Results in saline water (2.5%) showed a LOD and LOQ of 1.05 and 1.16 mg·L-1, respectively. Generally, performance was improved when moving from fresh to saline water. Studies on the dynamics of dissolved CO2 in a recirculating shallow raceway system (SRS+RAS) prototype showed higher precision than the tested commercial sensor. The new sensor is a compact and robust device, and unlike other sensors used in aquaculture, stirring is not required for correct and fast detection. Tests performed showed that this new sensor has a fast accurate detection as well as a strong potential for assessing dCO2 dynamics in aquaculture applications.
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Aquicultura/métodos , Dióxido de Carbono/análise , Águas Salinas/análise , Colorimetria , Monitoramento Ambiental/métodos , Fibras ÓpticasRESUMO
Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that recognize lipid antigens presented on CD1d molecules at the surface of antigen-presenting cells. GM2 is a glycosphingolipid abundant in cellular membranes and known to bind CD1d molecules, but the functional consequences of this binding are not completely clarified. Herein, we analyzed the effect of GM2 in iNKT cell activation. We found that culturing antigen-presenting cells or total peripheral blood mononuclear cells with GM2 did not induce activation of human iNKT cells, implying that this lipid is not antigenic for human iNKT cells. To investigate if this lipid could inhibit iNKT cell activation, we simultaneously incubated antigen-presenting cells with GM2 and the iNKT cell antigen α-Galactosylceramide (α-GalCer) and used them to stimulate iNKT cells. We found that GM2 reduced human iNKT cell activation in a dose-dependent manner. An explanation for this effect could be a direct competition of GM2 with antigenic lipids for CD1d binding. This was demonstrated by the use of an antibody (L363) that stains mouse CD1d:α-GalCer complexes, as in the presence of GM2 the amount of CD1d:α-GalCer complexes are reduced. We further explored the consequences of chronic GM2 overload on human iNKT cells by analyzing iNKT cells in patients diagnosed with GM2 gangliosidoses. We found that pediatric patients present a higher frequency of circulating CD4+ iNKT cells and concomitant lower frequency of CD4-CD8- iNKTs. A lower percentage of iNKT cells expressing the NK marker CD161 was also observed in these patients. In contrast, in two adult patients studied, no differences on iNKT cell phenotype were observed. Altogether, this study uncovers a new role for GM2 in the modulation of iNKT cell activation, thus strengthening the central role of lipid metabolism in iNKT cell biology.
Assuntos
Antígenos CD1d/genética , Galactosilceramidas/metabolismo , Gangliosidoses GM2/metabolismo , Glicoesfingolipídeos/metabolismo , Animais , Antígenos CD1d/metabolismo , Humanos , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/metabolismoRESUMO
BACKGROUND AND PURPOSE: Anterior temporal lobectomy for mesial temporal sclerosis (MTS) is a very effective measure for the control of seizures, and the probability of becoming seizure-free is approximately 70-90%. However, 30% of patients still experience seizures after surgery. An aura is a subjective ictal phenomenon that may precede an observable seizure. However, there are few studies on the prognostic factor aura although, being the initial symptoms of epileptic seizures, many types of auras have significant localizing or lateralizing value. This study hypothesized that the type of pre-operative aura may predict the post-surgical outcome in patients with medically refractory temporal lobe epilepsy due to MTS. METHODS: Of 1214 patients evaluated for surgery in the Epilepsy Center of Faculdade de Medicina de São Jose do Rio Preto (FAMERP), a tertiary Brazilian epilepsy center, 400 underwent anterior temporal lobectomy (ATL) for MTS. The number and type of auras were analyzed and compared with the Engel classification for outcome. RESULTS: Analyzing the patients by the type of aura, those who had extratemporal auras had the worst post-surgical result according to the Engel classification. Although mesial auras are apparently a good prognostic factor, patients without aura also had a worse prognosis. There were no differences between simple and multiple auras. To identify the most appropriate candidates for ATL, it is very important to consider the favorable prognostic factors for counseling patients in daily practice. CONCLUSIONS: Patients with symptoms and clinical signs that suggest extratemporal involvement may have unfavorable outcomes.
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Lobectomia Temporal Anterior , Epilepsia do Lobo Temporal/cirurgia , Epilepsia/complicações , Lobo Temporal/cirurgia , Adolescente , Adulto , Idoso , Brasil , Criança , Pré-Escolar , Epilepsia/patologia , Epilepsia/cirurgia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/patologia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Esclerose/patologia , Lobo Temporal/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, approximately 50-200 nucleotides in length, transcribed from the 5' end of polycomb target genes in primary T cells and embryonic stem cells. Short RNA transcription is associated with RNA polymerase II and H3K4me3, occurs in the absence of mRNA transcription, and is independent of polycomb activity. Short RNAs form stem-loop structures resembling PRC2 binding sites in Xist, interact with PRC2 through SUZ12, cause gene repression in cis, and are depleted from polycomb target genes activated during cell differentiation. We propose that short RNAs play a role in the association of PRC2 with its target genes.
Assuntos
RNA/metabolismo , Proteínas Repressoras/metabolismo , Transcrição Gênica , Animais , Sequência de Bases , Células Cultivadas , Cromatina/genética , Cromatina/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Histonas/genética , Histonas/metabolismo , Lisina/metabolismo , Camundongos , Dados de Sequência Molecular , Neurônios/citologia , Neurônios/fisiologia , Conformação de Ácido Nucleico , Proteínas do Grupo Polycomb , Regiões Promotoras Genéticas , RNA/química , RNA/genética , Proteínas Repressoras/genética , Linfócitos T/citologia , Linfócitos T/fisiologiaRESUMO
Zika virus is an emerging arbovirus, which is expanding in epidemic proportions through tropical and subtropical areas of the world. Although Zika is linked to a number of congenital and neurological complications, there is scarce knowledge on the impact of ZIKV infection in human skin. We report the case of a 68-year old woman who presented with generalized pustular psoriasis after a preceding and otherwise uneventful episode of ZIKV infection. Based on recent experimental data on the biology of ZIKV infection in the cutaneous environment, we speculate that ZIKV may have directly triggered the development of generalized pustular psoriasis by stimulation of keratinocyte-derived mediators of inflammation and a polyfunctional T-cell driven immune reaction in the cutaneous milieu.
Assuntos
Psoríase/virologia , Infecção por Zika virus/complicações , Zika virus , Idoso , Eritema/virologia , Feminino , Humanos , Pele/patologia , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnósticoRESUMO
Trypanosoma cruzi, the etiologic agent of Chagas disease, has to cope with reactive oxygen and nitrogen species during its life cycle in order to ensure its survival and infection. The parasite detoxifies these species through a series of pathways centered on trypanothione that depend on glutathione or low molecular mass dithiol proteins such as tryparedoxins. These proteins transfer reducing equivalents to peroxidases, including mitochondrial and cytosolic peroxiredoxins, TcMPx and TcCPx, respectively. In T. cruzi two tryparedoxins have been identified, TXNI and TXNII with different intracellular locations. TXNI is a cytosolic protein while TXNII due to a C-terminal hydrophobic tail is anchored in the outer membrane of the mitochondrion, endoplasmic reticulum and glycosomes. TXNs have been suggested to be involved in a majority of biological processes ranging from redox mechanisms to protein translation. Herein, a comparison of the TXNII interactomes under physiological and oxidative stress conditions was examined. Under physiological conditions, apart from the proteins with unknown biological process annotation, the majority of the identified proteins are related to cell redox homeostasis and biosynthetic processes, while under oxidative stress conditions, are involved in stress response, cell redox homeostasis, arginine biosynthesis and microtubule based process. Interestingly, although TXNII interacts with both peroxiredoxins under physiological conditions, upon oxidative stress, TcMPx interaction prevails. The relevance of the interactions is discussed opening a new perspective of TXNII functions.