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1.
BMC Biol ; 20(1): 233, 2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36266680

RESUMO

BACKGROUND: Lipid homeostasis is an evolutionarily conserved process that is crucial for energy production, storage and consumption. Drosophila larvae feed continuously to achieve the roughly 200-fold increase in size and accumulate sufficient reserves to provide all energy and nutrients necessary for the development of the adult fly. The mechanisms controlling this metabolic program are poorly understood. RESULTS: Herein we identified a highly conserved gene, orsai (osi), as a key player in lipid metabolism in Drosophila. Lack of osi function in the larval fat body, the regulatory hub of lipid homeostasis, reduces lipid reserves and energy output, evidenced by decreased ATP production and increased ROS levels. Metabolic defects due to reduced Orsai (Osi) in time trigger defective food-seeking behavior and lethality. Further, we demonstrate that downregulation of Lipase 3, a fat body-specific lipase involved in lipid catabolism in response to starvation, rescues the reduced lipid droplet size associated with defective orsai. Finally, we show that osi-related phenotypes are rescued through the expression of its human ortholog ETFRF1/LYRm5, known to modulate the entry of ß-oxidation products into the electron transport chain; moreover, knocking down electron transport flavoproteins EtfQ0 and walrus/ETFA rescues osi-related phenotypes, further supporting this mode of action. CONCLUSIONS: These findings suggest that Osi may act in concert with the ETF complex to coordinate lipid homeostasis in the fat body in response to stage-specific demands, supporting cellular functions that in turn result in an adaptive behavioral response.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Metabolismo dos Lipídeos , Animais , Humanos , Trifosfato de Adenosina/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Corpo Adiposo/metabolismo , Flavoproteínas/metabolismo , Larva , Lipase/genética , Lipase/metabolismo , Metabolismo dos Lipídeos/genética , Lipídeos , Espécies Reativas de Oxigênio/metabolismo
2.
Infect Immun ; 88(4)2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-31964743

RESUMO

Invasive aspergillosis (IA) is a life-threatening infection that affects an increasing number of patients undergoing chemotherapy or allo-transplantation, and recent studies have shown that genetic factors contribute to disease susceptibility. In this two-stage, population-based, case-control study, we evaluated whether 7 potentially functional single nucleotide polymorphisms (SNPs) within the ARNT2 and CX3CR1 genes influence the risk of IA in high-risk hematological patients. We genotyped selected SNPs in a cohort of 500 hematological patients (103 of those had been diagnosed with proven or probable IA), and we evaluated their association with the risk of developing IA. The association of the most interesting markers of IA risk was then validated in a replication population, including 474 subjects (94 IA and 380 non-IA patients). Functional experiments were also performed to confirm the biological relevance of the most interesting markers. The meta-analysis of both populations showed that carriers of the ARNT2rs1374213G, CX3CR1rs7631529A, and CX3CR1rs9823718G alleles (where the RefSeq identifier appears as a subscript) had a significantly increased risk of developing IA according to a log-additive model (P value from the meta-analysis [PMeta] = 9.8 · 10-5, PMeta = 1.5 · 10-4, and PMeta =7.9 · 10-5, respectively). Haplotype analysis also confirmed the association of the CX3CR1 haplotype with AG CGG with an increased risk of IA (P = 4.0 · 10-4). Mechanistically, we observed that monocyte-derived macrophages (MDM) from subjects carrying the ARNTR2rs1374213G allele or the GG genotype showed a significantly impaired fungicidal activity but that MDM from carriers of the ARNT2rs1374213G and CX3CR1rs9823718G or CX3CR1rs7631529A alleles had deregulated immune responses to Aspergillus conidia. These results, together with those from expression quantitative trait locus (eQTL) data browsers showing a strong correlation of the CX3CR1rs9823718G allele with lower levels of CX3CR1 mRNA in whole peripheral blood (P = 2.46 · 10-7) and primary monocytes (P = 4.31 · 10-7), highlight the role of the ARNT2 and CX3CR1 loci in modulating and predicting IA risk and provide new insights into the host immune mechanisms involved in IA development.


Assuntos
Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Aspergillus/imunologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Receptor 1 de Quimiocina CX3C/genética , Predisposição Genética para Doença , Aspergilose Pulmonar Invasiva/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Genótipo , Doenças Hematológicas/complicações , Humanos , Medição de Risco
3.
RNA Biol ; 16(3): 295-308, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30734641

RESUMO

Viroids are small infectious, non-protein-coding circular RNAs that replicate independently and, in some cases, incite diseases in plants. They are classified into two families: Pospiviroidae, composed of species that have a central conserved region (CCR) and replicate in the cell nucleus, and Avsunviroidae, containing species that lack a CCR and whose multimeric replicative intermediates of either polarity generated in plastids self-cleave through hammerhead ribozymes. The compact, rod-like or branched, secondary structures of viroid RNAs have been predicted by RNA folding algorithms and further examined using different in vitro and in vivo experimental techniques. However, direct data about their native tertiary structure remain scarce. Here we have applied atomic force microscopy (AFM) to image at single-molecule resolution different variant RNAs of three representative viroids: potato spindle tuber viroid (PSTVd, family Pospiviroidae), peach latent mosaic viroid and eggplant latent viroid (PLMVd and ELVd, family Avsunviroidae). Our results provide a direct visualization of their native, three-dimensional conformations at 0 and 4 mM Mg2+ and highlight the role that some elements of tertiary structure play in their stabilization. The AFM images show that addition of 4 mM Mg2+ to the folding buffer results in a size contraction in PSTVd and ELVd, as well as in PLMVd when the kissing-loop interaction that stabilizes its 3D structure is preserved.


Assuntos
Microscopia de Força Atômica , Conformação de Ácido Nucleico , RNA Viral/química , Imagem Individual de Molécula , Viroides/genética , Microscopia de Força Atômica/métodos , Vírus de Plantas/genética , Vírus de Plantas/ultraestrutura , Imagem Individual de Molécula/métodos
4.
J Anat ; 232(4): 699-715, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29315537

RESUMO

Its high metabolic rate and high polyunsaturated fatty acid content make the brain very sensitive to oxidative damage. In the brain, neuronal metabolism occurs at a very high rate and generates considerable amounts of reactive oxygen species and free radicals, which accumulate inside neurons, leading to altered cellular homeostasis and integrity and eventually irreversible damage and cell death. A misbalance in redox metabolism and the subsequent neurodegeneration increase throughout the course of normal aging, leading to several age-related changes in learning and memory as well as motor functions. The neuroprotective function of antioxidants is crucial to maintain good brain homeostasis and adequate neuronal functions. Vitamins E and C are two important antioxidants that are taken up by brain cells via the specific carriers αTTP and SVCT2, respectively. The aim of this study was to use immunohistochemistry to determine the distribution pattern of these vitamin transporters in the brain in a mouse model that shows fewer signs of brain aging and a higher resistance to oxidative damage. Both carriers were distributed widely throughout the entire brain in a pattern that remained similar in 4-, 12-, 18- and 24-month-old mice. In general, αTTP and SVCT2 were located in the same regions, but they seemed to have complementary distribution patterns. Double-labeled cell bodies were detected only in the inferior colliculus, entorhinal cortex, dorsal subiculum, and several cortical areas. In addition, the presence of αTTP and SVCT2 in neurons was analyzed using double immunohistochemistry for NeuN and the results showed that αTTP but not SVCT2 was present in Bergmann's glia. The presence of these transporters in brain regions implicated in learning, memory and motor control provides an anatomical basis that may explain the higher resistance of this animal model to brain oxidative stress, which is associated with better motor performance and learning abilities in old age.


Assuntos
Envelhecimento/metabolismo , Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Estresse Oxidativo , Transportadores de Sódio Acoplados à Vitamina C/metabolismo , Animais , Antígenos Nucleares/metabolismo , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Biomarcadores/metabolismo , Encéfalo/diagnóstico por imagem , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica/métodos , Aprendizagem , Masculino , Memória , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/metabolismo , Neuroglia/ultraestrutura , Neurônios/metabolismo , Neurônios/ultraestrutura , Vitamina E/metabolismo
5.
Nanotechnology ; 29(35): 355707, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-29888710

RESUMO

Core-shell gallium nanoparticles (Ga NPs) have recently been proposed as an ultraviolet plasmonic material for different applications but only at room temperature. Here, the thermal stability as a function of the size of the NPs is reported over a wide range of temperatures. We analyze the chemical and structural properties of the oxide shell by x-ray photoelectron spectroscopy and atomic force microscopy. We demonstrate the inverse dependence of the shell breaking temperature with the size of the NPs. Spectroscopic ellipsometry is used for tracking the rupture and its mechanism is systematically investigated by scanning electron microscopy, grazing incidence x-ray diffraction and cathodoluminescence. Taking advantage of the thermal stability of the NPs, we perform complete oxidations that lead to homogenous gallium oxide NPs. Thus, this study set the physical limits of Ga NPs to last at high temperatures, and opens up the possibility to achieve totally oxidized NPs while keeping their sphericity.

6.
Doc Ophthalmol ; 136(3): 157-164, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29779071

RESUMO

PURPOSE: To investigate within-test variability of the steady-state PERG (SS-PERG). METHODS: SS-PERGs were recorded in response to black-white horizontal gratings (1.6 cycles/deg, 98% contrast, 15.63 reversals/s, LED display, 25 deg square field, 800 cd/sqm mean luminance) using skin electrodes. PERG and noise (± reference) signals were averaged over 1024 epochs (~ 2.2 min) and Fourier analyzed to retrieve SS-PERG amplitude and phase. SS-PERGs were split into 16 partial averages (samples) of 64 epochs each, and corresponding amplitudes and phases combined in polar coordinates to assess their dispersion (within-test variability). To assess time-dependent variability, samples were clustered in four successive time segments of ~ 33 s each. Amplitude adaptation was defined as amplitude difference between initial and final clusters, and PERG phase adaptation as the corresponding phase difference. To determine the dynamic range of SS-PERG adaptation, recording was performed in normal controls of different age (n = 32) and patients with different severity of optic nerve dysfunction (early manifest glaucoma, EMG, n = 7; non-arteritic ischemic optic neuropathy, NAION, n = 5). RESULTS: Amplitude adaptation was largest in younger controls (amplitude adaptation ÷ noise, SNR = 9.5, 95% CI 13.1, 5.9) and progressively decreased with increasing age (older subjects, SNR = 5.5, 95% CI 9.2, 1.8) and presence of disease (EMG: SNR = 2.4, 95% CI 3.5, 1.4; NAION: SNR = 1.9, 95% CI 6.5,-2.2). In 11 young subjects, amplitude adaptation was repeatable (test-retest in two sessions a week apart; intraclass correlation coefficient = 0.59). Phase adaptation was not significantly different from zero in all groups. CONCLUSIONS: SS-PERG adaptation accounts for a sizeable portion of the within-test variability. As it has robust SNR, sufficient test-retest variability, and is altered in disease, it may have physiological and clinical significance. This study suggests that SS-PERG protocols should include adaptation in addition to SS-PERG amplitude and phase/latency.


Assuntos
Eletrorretinografia/métodos , Glaucoma/fisiopatologia , Neuropatia Óptica Isquêmica/fisiopatologia , Células Ganglionares da Retina/fisiologia , Adulto , Idoso , Eletrodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reconhecimento Visual de Modelos/fisiologia , Adulto Jovem
7.
Langmuir ; 33(17): 4269-4279, 2017 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-28391698

RESUMO

Since the past decade, there has been growing interest to grant nanoparticles with diffusion properties across mucosae. In this sense, the nonionic block copolymer Pluronic F127 (PF127) has emerged as a promising coating agent to formulate mucus-penetrating particles. In the journey to find efficient coating agents, researchers have focused more on the effect of the coating agent architecture rather than on the role of the physicochemical properties of the nanoparticle used as the substrate. The current knowledge about mucodiffusive particles is in general based on model-like nanoparticles, such as polystyrene or poly(lactic-co-glycolic) acid nanoparticles, but there is a lack of information about the potential of PF127 on other colloidal systems. This work aims to shed some light on this issue by selecting three oils, palm (solid), coconut (semisolid), and wheat germ (liquid), with different physicochemical properties to formulate PF127-coated nanoemulsions. The obtained nanoemulsions were characterized, and their colloidal stability was tested. Their diffusion capacity was determined by particle tracking after challenging the nanoemulsions across an intestinal porcine mucus layer. In accordance with the evidence of model-like nanoparticles, our results state that PF127 allows mucodiffusion, but its effectiveness as a coating agent clearly depends on the physicochemical properties of the nanostructure core over which PF127 is placed. Among other physicochemical properties, the results certainly showed that the hydrophobic character of the nanostructure core emerges as a critical factor in the formulation of successful PF127 coatings.


Assuntos
Emulsões/química , Excipientes/química , Nanopartículas/química , Poloxâmero/química , Tensoativos/química , Administração Oral , Animais , Óleo de Coco/química , Difusão , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Muco/química , Óleo de Palmeira/química , Pancreatina/química , Tamanho da Partícula , Pepsina A/química , Óleos de Plantas/química , Suínos , alfa-Tocoferol/química
8.
J Anim Physiol Anim Nutr (Berl) ; 101(4): 723-732, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27121753

RESUMO

The dietary contents of crude protein and free amino acids (AA) may affect the protein digestion and AA absorption in pigs. Trypsin and chymotrypsin activities, AA serum concentrations and expression of AA transporters in the small intestine of pigs fed a low protein, AA-supplemented (19.2%, LPAA) or a high protein (28.1%, HP), wheat-soybean meal diet were measured in two 14-d trials. The LPAA diet contained free L-Lys, L-Thr, DL-Met, L-Leu, L-Ile, L-Val, L-His, L-Trp and L-Phe. All pigs were fed the same amount of feed (890 and 800 g/d for trial 1 and 2 respectively). In trial 1, samples of mucosa (duodenum, jejunum and ileum) and digesta (duodenum and jejunum) were collected from 14 pigs (17.2 ± 0.4 kg); in trial 2, blood samples were collected from 12 pigs (12.7 ± 0.3 kg). The trypsin and chymotrypsin activities in both intestinal segments were higher in pigs fed the HP diet (p < 0.01). Trypsin activity was higher in jejunum than in duodenum regardless the dietary treatment (p < 0.05). Pigs fed the LPAA diet expressed more b0,+ AT in duodenum, B0 AT1 in ileum (p < 0.05), and tended to express more y+ LAT1 in duodenum (p = 0.10). In pigs fed the LPAA diet, the expression of b0,+ AT was higher in duodenum than in jejunum and ileum (p < 0.01), but no difference was observed in pigs fed the HP diet. Ileum had the lowest b0,+ AT expression regardless the diet. The serum concentrations of Lys, Thr and Met were higher in LPAA pigs while serum Arg was higher in HP pigs (p < 0.05). Serum concentrations of AA appear to reflect the AA absorption. In conclusion, these data indicate that the dietary protein contents affect the extent of protein digestion and that supplemental free AA may influence the intestinal site of AA release and absorption, which may impact their availability for growth of young pigs.


Assuntos
Aminoácidos/farmacologia , Ração Animal/análise , Proteínas Alimentares/farmacologia , Pâncreas/enzimologia , Peptídeo Hidrolases/metabolismo , Suínos/fisiologia , Sistemas de Transporte de Aminoácidos/metabolismo , Aminoácidos/sangue , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeo Hidrolases/genética
9.
Nanotechnology ; 27(44): 444001, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27670245

RESUMO

We have produced self-organised silicide nanodot patterns by medium-energy ion beam sputtering (IBS) of silicon targets with a simultaneous and isotropic molybdenum supply. Atomic force microscopy (AFM) studies show that these patterns are qualitatively similar to those produced thus far at low ion energies. We have determined the relevance of the ion species on the pattern ordering and properties. For the higher ordered patterns produced by Xe(+) ions, the pattern wavelength depends linearly on the ion energy. The dot nanostructures are silicide-rich as assessed by x-ray photoelectron spectroscopy (XPS) and emerge in height due to their lower sputtering yield, as observed by electron microscopy. Remarkably, a long wavelength corrugation is observed on the surface which is correlated with both the Mo content and the dot pattern properties. Thus, as assessed by electron microscopy, the protrusions are Mo-rich with higher and more spaced dots on their surface whereas the valleys are Mo-poor with smaller dots that are closer to each other. These findings indicate that there is a correlation between the local metal content of the surface and the nanodot pattern properties both at the nanodot and the large corrugation scales. These results contribute to advancing the understanding of this interesting nanofabrication method and aid in developing a comprehensive theory of nanodot pattern formation and evolution.

11.
Phys Chem Chem Phys ; 18(42): 29218-29225, 2016 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-27731445

RESUMO

The morphology as well as the electric and electronic properties of aryl diazonium, in particular 4-nitrobenzene-diazonium (NBD), films on HOPG surfaces have been studied at the nanoscale level. By controlling the 2,2-diphenyl-1-picrylhydrazyl concentration during the NBD film growth, we have been able to control the thickness of the layer. The implications of NBD submonolayer adsorption on the electrical properties of this system have been analysed through Density Functional Theory (DFT) calculations, Atomic Force (AFM), Electric Force (EFM) and Kelvin Probe Force (KPFM) microscopies. DFT simulations showed that the NBD molecule adsorbs almost perpendicularly to the HOPG surface, which was confirmed experimentally through AFM imaging in the dynamic mode. In addition, DFT calculations showed that the adsorbed NBD has an appreciable dipole moment directed towards the HOPG surface and along the vertical direction of the HOPG surface. The existence of this dipole is the origin of the EFM contrast observed between the NBD-free and NBD-covered regions when a bias of -2 V was applied to the tip. Besides, the KPFM measurements show that the NBD adsorption leads to higher work function values, which is in agreement with the DFT calculations. Noticeably, our studies show that the KPFM signal is sensitive to the partial NBD coverage of the HOPG surface below the monolayer level.

12.
Inflammopharmacology ; 24(2-3): 127-31, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27188987

RESUMO

Alkylglycerols (AKGs), isolated or present in shark liver oil have anti-inflammatory properties. Complement 3 (C3) and 4 (C4) participate in lipid metabolism and in obesity, contributing to the metabolic syndrome and to the low-grade inflammation associated with obesity. In a randomized, controlled, crossover study, 26 non-diabetes obese individuals were assigned two preparations with low (LAC, 10 mg AKGs) and high (HAC, 20 mg AKGs) AKG content. Intervention periods were of 3 weeks preceded by 2-week washout periods in which shark liver oil was avoided. Cholesterol, C3, C4, and vascular endothelial growth factor (VEGF) decreased in a linear trend (P < 0.01) from baseline (control) to LAC and HAC. Values after HAC were significantly lower (P < 0.05) versus both baseline and after LAC. No adverse effects were observed or reported. Data from this pilot study open a promising field for the study of the beneficial effects of AKGs on cardiovascular risk factors in obese individuals.


Assuntos
Anti-Inflamatórios/administração & dosagem , Óleos de Peixe/administração & dosagem , Glicerol/administração & dosagem , Obesidade/sangue , Obesidade/dietoterapia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Anti-Inflamatórios/isolamento & purificação , Biomarcadores/sangue , Estudos Cross-Over , Método Duplo-Cego , Feminino , Óleos de Peixe/isolamento & purificação , Glicerol/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Projetos Piloto , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto Jovem
13.
Med Intensiva ; 40(7): 422-30, 2016 Oct.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-26976118

RESUMO

OBJECTIVE: To identify risk factors for worsened quality of life (QoL) and activities of daily living (ADL) at 3 and 12 months after discharge from the Intensive Care Unit (ICU) in patients on mechanical ventilation (MV). DESIGN: A prospective, multicentric observational study was made. SETTING: Three ICUs in Argentina. PATIENTS: The study included a total of 84 out of 129 mainly clinical patients admitted between 2011-2012 and requiring over 24hours of MV. INTERVENTIONS: No interventions were carried out. VARIABLES: Quality of life was assessed with the EQ-5D (version for Argentina), and ADL with the Barthel index. RESULTS: The EQ-5D and Barthel scores were assessed upon admission to the ICU (baseline) and after three months and one year of follow-up. Comorbidities, delirium, ICU acquired weakness (ICUAW), and medication received were daily assessed during ICU stay. The baseline QoL of the global sample showed a median index of [0.831 (IQR25-75% 0.527-0.931)], versus [0.513 (IQR0.245-0.838)] after three months and [0.850 (IQR0.573-1.00)] after one year. Significant differences were observed compared with QoL in the Argentinean general population [mean 0.880 (CI 0.872-0.888), p<0.001; p<0.001; p0.002]. Individual analysis showed that 67% of the patients had worsened their QoL at three months, while 33% had recovered their QoL. In the multivariate analysis, the variables found to be independent predictors of worsened QoL were a hospital stay ≥21 days [OR 12.57 (2.75-57.47)], age ≥50 years [OR 5.61 (1.27-24.83)], previous poor QoL [OR 0.11 (0.02-0.54)] and persistent ICUAW [OR 8.32 (1.22-56.74)]. Similar results were found for the worsening of ADL. CONCLUSIONS: Quality of life is altered after critical illness, and its recovery is gradual over time. Age, length of hospital stay, previous QoL and persistent ICUAW seem to be risk factors for worsened QoL.


Assuntos
Qualidade de Vida , Respiração Artificial , Atividades Cotidianas , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Estudos Prospectivos , Fatores de Risco
14.
Infect Immun ; 84(3): 643-57, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26667837

RESUMO

Recent studies suggest that immune-modulating single-nucleotide polymorphisms (SNPs) influence the risk of developing cancer-related infections. Here, we evaluated whether 36 SNPs within 14 immune-related genes are associated with the risk of invasive aspergillosis (IA) and whether genotyping of these variants might improve disease risk prediction. We conducted a case-control association study of 781 immunocompromised patients, 149 of whom were diagnosed with IA. Association analysis showed that the IL4Rrs2107356 and IL8rs2227307 SNPs (using dbSNP numbering) were associated with an increased risk of IA (IL4Rrs2107356 odds ratio [OR], 1.92; 95% confidence interval [CI], 1.20 to 3.09; IL8rs2227307 OR, 1.73; 95% CI, 1.06 to 2.81), whereas the IL12Brs3212227 and IFNγrs2069705 variants were significantly associated with a decreased risk of developing the infection (IL12Brs3212227 OR, 0.60; 95% CI, 0.38 to 0.96; IFNγrs2069705 OR, 0.63; 95% CI, 0.41 to 0.97). An allogeneic hematopoietic stem cell transplantation (allo-HSCT)-stratified analysis revealed that the effect observed for the IL4Rrs2107356 and IFNγrs2069705 SNPs was stronger in allo-HSCT (IL4Rrs2107356 OR, 5.63; 95% CI, 1.20 to 3.09; IFNγrs2069705 OR, 0.24; 95% CI, 0.10 to 0.59) than in non-HSCT patients, suggesting that the presence of these SNPs renders patients more vulnerable to infection, especially under severe and prolonged immunosuppressive conditions. Importantly, in vitro studies revealed that carriers of the IFNγrs2069705C allele showed a significantly increased macrophage-mediated neutralization of fungal conidia (P = 0.0003) and, under stimulation conditions, produced higher levels of gamma interferon (IFNγ) mRNA (P = 0.049) and IFNγ and tumor necrosis factor alpha (TNF-α) cytokines (P value for 96 h of treatment with lipopolysaccharide [PLPS-96 h], 0.057; P value for 96 h of treatment with phytohemagglutinin [PPHA-96 h], 0.036; PLPS+PHA-96 h = 0.030; PPHA-72 h = 0.045; PLPS+PHA-72 h = 0.018; PLPS-96 h = 0.058; PLPS+PHA-96 h = 0.0058). Finally, we also observed that the addition of SNPs significantly associated with IA to a model including clinical variables led to a substantial improvement in the discriminatory ability to predict disease (area under the concentration-time curve [AUC] of 0.659 versus AUC of 0.564; P-2 log likehood ratio test = 5.2 · 10(-4) and P50.000 permutation test = 9.34 · 10(-5)). These findings suggest that the IFNγrs2069705 SNP influences the risk of IA and that predictive models built with IFNγ, IL8, IL12p70, and VEGFA variants can used to predict disease risk and to implement risk-adapted prophylaxis or diagnostic strategies.


Assuntos
Aspergilose/genética , Aspergilose/imunologia , Predisposição Genética para Doença , Interferon gama/genética , Subunidade p40 da Interleucina-12/genética , Subunidade alfa de Receptor de Interleucina-4/genética , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Hospedeiro Imunocomprometido/genética , Interferon gama/imunologia , Subunidade p40 da Interleucina-12/imunologia , Subunidade alfa de Receptor de Interleucina-4/imunologia , Interleucina-8/imunologia , Masculino , Pessoa de Meia-Idade
15.
Transpl Infect Dis ; 17(2): 221-33, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25652036

RESUMO

BACKGROUND: Umbilical cord blood transplantation (CBT) is an established alternative source of stem cells in the setting of unrelated transplantation. When compared with other sources, single-unit CBT (sCBT) is associated with a delayed hematologic recovery, which may lead to a higher infection-related mortality (IRM). Co-infusion with the sCBT of CD34+ peripheral blood stem cells from a third-party donor (TPD) (sCBT + TPDCD34+) has been shown to markedly accelerate leukocyte recovery, potentially reducing the IRM. However, to our knowledge, no comparative studies have focused on severe infections and IRM with these 2 sCBT strategies. METHODS: A total of 148 consecutive sCBT (2000-2010, median follow-up 4.5 years) were included in a multicenter retrospective study to analyze the incidence and risk factors of IRM and severe viral and invasive fungal infections (IFIs). Neutrophil engraftment occurred in 90% of sCBT (n = 77) and 94% sCBT + TPDCD34+ (n = 71) recipients at a median of 23 and 12 days post transplantation, respectively (P < 0.01). RESULTS: The 4-year IRM was 24% and 20%, respectively (P = 0.7), with no differences at day +30 (5% and 4%, respectively) and day +100 (10% and 8%, respectively). In multivariate analysis early status of the underlying malignancy, cytomegalovirus (CMV)-seronegative recipient and high CD34+ cell content in the cord blood unit before cryostorage (≥1.4 × 10(5) /kg) were protective of IRM. Among the causes of IRM, bacterial infections and IFIs were more common in sCBT (15% vs. 4%), while CMV disease and parasitic infections were more common in the sCBT + TPDCD34+ cohort (5% vs. 16%). CONCLUSION: These data show that sCBT supported with TPDCD34(+) cells results in much shorter periods of post-transplant leukopenia, but the short- and long-term rates of IRM were comparable to those of sCBT, presumably because immune recovery is equally delayed in both graft types.


Assuntos
Infecções Bacterianas/epidemiologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Imunossupressores/uso terapêutico , Leucemia/terapia , Linfoma/terapia , Micoses/epidemiologia , Agonistas Mieloablativos/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/métodos , Viroses/epidemiologia , Adolescente , Adulto , Antígenos CD34 , Infecções Bacterianas/mortalidade , Bussulfano/uso terapêutico , Estudos de Coortes , Ciclosporina/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Micoses/mortalidade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Tiotepa/uso terapêutico , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Viroses/mortalidade , Irradiação Corporal Total , Adulto Jovem
16.
J Appl Microbiol ; 119(6): 1692-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26434743

RESUMO

AIMS: The objective of this study was to produce stable inclusions of chitinase ChiA74Δsp in Bacillus thuringiensis subsp. israelensis (Bti) and to assay its insecticidal activity against Aedes aegypti larvae. METHODS AND RESULTS: Bti was transformed with chiA74Δsp regulated by its own promoter or by the strong chimeric cytAp/STAB-SD promoter system to generate two recombinant Bti strains. These recombinants produced their native parasporal bodies composed of Cry4Aa, Cry4Ba, Cry11Aa and Cyt1Aa and ChiA74Δsp inclusions, and showed a approx. threefold increase in both endochitinase activity and viable spore count when compared with the parental strain. Both recombinants were approximately twofold more toxic (LC50s 8·02, 9·6 ng ml(-1) ) than parental Bti (19·8 ng ml(-1) ) against 4(th) instars of A. aegypti larvae. CONCLUSIONS: ChiA74Δsp inclusions, together with the insecticidal crystals and spores of Bti increased the toxicity against A. aegypti larvae by at least twofold. SIGNIFICANCE AND IMPACT OF THE STUDY: We report for the first time the engineering of Bti to produce spore-parasporal body-ChiA74∆sp inclusions in the same sporangium, which are released together following autolysis. Our work lays a foundation for engineering Bti to produce more efficacious combinations of Cry4Aa, Cry4Ba, Cry11Aa, Cyt1Aa and chitinase inclusions.


Assuntos
Aedes/efeitos dos fármacos , Bacillus thuringiensis , Proteínas de Bactérias , Quitinases , Inseticidas , Larva/efeitos dos fármacos , Animais , Bacillus thuringiensis/enzimologia , Bacillus thuringiensis/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/farmacologia , Quitinases/metabolismo , Quitinases/farmacologia , Inseticidas/metabolismo , Inseticidas/farmacologia
17.
Phys Rev Lett ; 112(9): 094103, 2014 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-24655256

RESUMO

We report the experimental observation of a submicron cellular structure on the surface of silicon targets eroded by an ion plasma. Analysis by atomic force microscopy allows us to assess the time evolution and show that the system can be described quantitatively by the convective Cahn-Hilliard equation, found in the study of domain coarsening for a large class of driven systems. The space-filling trait of the ensuing pattern relates it to evolving foams. Through this connection, we are actually able to derive the coarsening law for the pattern wavelength from the nontrivial topological dynamics of the cellular structure. Thus, the study of the topological properties of patterns in nonvariational spatially extended systems emerges as complementary to morphological approaches to their challenging coarsening properties.

18.
Nanotechnology ; 25(41): 415301, 2014 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-25248515

RESUMO

We address the impact of metal co-deposition in the nanodot patterning dynamics of Si(100) surfaces under normal-incidence 1 keV Ar(+) ion-beam sputtering (IBS). In particular, the effect of both the metal nature (Fe or Mo) and flux has been studied. Morphological and compositional evolution were followed by atomic force microscopy (AFM) and Rutherford backscattering spectrometry, respectively. For the same type of impurity, the dynamics is faster for a higher co-deposition flux, which also drives to larger asymptotic roughness and wavelength. Mo co-deposition yields rougher surfaces for a lower metal coverage than Fe and, remarkably, higher ordered patterns. X-ray photoelectron spectroscopy reveals the formation of silicide bonds even before pattern onset, stressing the relevant role of the affinity of the co-deposited metals for silicon. Further, current-sensing AFM performed at the initial and asymptotic stages indicates that the nanodot structures are metal-rich, resulting in coupled compositional and morphological patterns. These results are discussed in terms of phase segregation, morphology-driven local flux variations of impurities and silicide formation. This analysis reveals that the underlying (concurrent) mechanisms of pattern formation are complex since many processes can come into play with a different relative weight depending on the specific patterning conditions. From a practical point of view, it is shown that, by proper selection of the process parameters, IBS with metal co-deposition can be used to tune the dynamics and pattern properties and, interestingly, to produce highly ordered arrays.

19.
Anal Bioanal Chem ; 406(29): 7483-95, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24817353

RESUMO

The roughness induced during glow-discharge optical-emission spectroscopy (GDOES) measurements has been reported to cause a loss of resolution during GDOES depth-profiling analysis. In this paper, we undertake for the first time a study of the dynamics of the surface morphology of chromium and titanium thin films (designed in mono and multilayer structures) under the impinging of GDOES incoming ions. We performed this study under the theoretical framework of the dynamic scaling theory, by analysing surface morphology changes, as measured ex-situ by AFM, with irradiation time. For single metal layers it was found that, after an initial surface smoothening, the surface undergoes a rapid steep roughening for both systems, with quite similar quantitative dynamics. Once this roughening ends a second temporal scaling regime arises, operating for long length scales with dynamics depending on the sputtering rate of the material. For the chromium layer, with a very high sputtering rate of 5.5 µm min(-1), this regime is consistent with the KPZ model, whereas for the titanium layer an EW scaling regime is indicated. These different scaling regimes are consistent with the development of larger surface slopes for the Cr system. In the multilayer systems, the initial roughness induced on the top Cr layer by GDOES has similar dynamics to that for single-layer Cr. However, a clear decrease in the roughness was observed once the underlying Ti layer, with a lower sputtering rate, was reached. This decrease in the induced roughness is maintained while the Ti layer is eroded. Therefore, choice of appropriate material (i.e. sputtering yield values) combinations and of their depth of location can enable tuning of GDOES-induced roughness and achieve substantial control over the depth profiling process.

20.
Int J Drug Policy ; 123: 104281, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38056222

RESUMO

INTRODUCTION: This study aimed to evaluate the feasibility of molecular point-of-care testing for STIs, the prevalence of STIs and associated factors, and testing and treatment uptake among street-based female sex workers (FSWs) attending a mobile harm reduction unit in Madrid, Spain. METHODS: This was a prospective, longitudinal study. From August 15th to December 6th, 2022, participants were screened for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis using molecular testing (Xpert) on self-collected urine samples at a mobile harm reduction unit. Additionally, rapid tests were used to screen participants for HIV, hepatitis C virus (HCV), and syphilis. On-site same-day results and treatment for those infected were offered. RESULTS: Among 77 FSWs included the median age was 40 (range, 33-48), 64 % were homeless, and 84 % reported drug use in the past six months. Four participants self-reported having HIV, of whom all were on antiretroviral therapy, and 14 (18 %) had HCV antibodies, including three with current infection. The prevalence of at least one STI was 66 %. When categorized by type of STI, the prevalences were as follows: 15 % for CT, 15 % for NG, 51 % for TV, and 21 % for syphilis. Notably, the prevalence of STIs was higher among FSW with recent drug use, with no cases of CT or NG detected among FSWs who did not recently use drugs. In adjusted analysis, drug use was associated an increased odds of having an STI (adjusted odds ratio, 10.47; 95 % CI: 1.67-65.42). All participants consented to screening, and all but one received on-site result-based linkage to treatment. CONCLUSIONS: This study demonstrates the feasibility, high STI prevalence, and high linkage to testing and treatment following point-of-care molecular testing among street-based FSWs who have recently used drugs in Madrid, Spain.


Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Profissionais do Sexo , Infecções Sexualmente Transmissíveis , Sífilis , Feminino , Humanos , Adulto , Sífilis/diagnóstico , Sífilis/epidemiologia , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Redução do Dano , Espanha/epidemiologia , Estudos Prospectivos , Estudos Longitudinais , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/terapia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Testes Imediatos , Prevalência
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