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Daily oral pre-exposure prophylaxis (PrEP) offers effective HIV prevention. In South Africa, PrEP is publicly available, but use among young women remains low. We explored young women's perceptions of PrEP to inform a gender-focused intervention to promote PrEP uptake. Six focus group discussions and eight in-depth interviews exploring perceptions of PrEP were conducted with forty-six women not using PrEP, ages 18-25, from central Durban. Data were thematically analyzed using a team-based consensus approach. The study was conducted among likely PrEP users: women were highly-educated, with 84.8% enrolled in post-secondary education. Qualitative data revealed intersecting social stigmas related to HIV and women's sexuality. Women feared that daily PrEP pills would be confused with anti-retroviral treatment, creating vulnerability to misplaced HIV stigma. Women also anticipated that taking PrEP could expose them to assumptions of promiscuity from the community. To address these anticipated community-level reactions, women suggested community-facing interventions to reduce the burden on young women considering PrEP. Concerns around PrEP use in this group of urban, educated women reflects layered stigmas that may inhibit future PrEP use. Stigma-reducing strategies, such as media campaigns and educational interventions directed at communities who could benefit from PrEP, should re-frame PrEP as an empowering and responsible choice for young women.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Sexualidad , Estigma Social , Sudáfrica/epidemiología , Adulto JovenRESUMEN
Negative thermal expansion is an unusual phenomenon appearing in only a handful of materials, but pursuit and mastery of the phenomenon holds great promise for applications across disciplines and industries. Here we report use of x-ray spectroscopy and diffraction to investigate the 4f-electronic properties in Y-doped SmS and employ the Kondo volume collapse model to interpret the results. Our measurements reveal an unparalleled decrease of the bulk Sm valence by over 20% at low temperatures in the mixed-valent golden phase, which we show is caused by a strong coupling between an emergent Kondo lattice state and a large isotropic volume change. The amplitude and temperature range of the negative thermal expansion appear strongly dependent on the Y concentration and the associated chemical disorder, providing control over the observed effect. This finding opens avenues for the design of Kondo lattice materials with tunable, giant, and isotropic negative thermal expansion.
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OBJECTIVE: To describe the receipt of a diagnosis, referral and treatment for depression in people receiving antiretroviral therapy (ART), with depressive symptoms and attending primary care clinics in South Africa, and investigate factors associated with receiving these components of care. METHODS: This is a secondary analysis of data from a randomised controlled trial of an intervention intended to improve detection and treatment of depression in primary care patients receiving ART. In this analysis, we combined cross-sectional and longitudinal data from the intervention and control arms. Using regression models and adjusting for intra-cluster correlation of outcomes, we investigated associations between socioeconomic characteristics, depressive symptoms, stress, disability and stigma, and receipt of a diagnosis, referral and treatment for depression. RESULTS: Of 2002 participants enrolled, 18% reported a previous diagnosis of depression by a healthcare worker and 10% reported having received counselling from a specialist mental health worker. Diagnosis, referral and counselling during the follow-up period were appropriately targeted, being independently more frequent in participants with higher enrolment scores for depressive symptoms, stress or disability. Participants with higher stigma scores at enrolment were independently less likely to receive counselling. Severe socio-economic deprivation was common but was not associated with treatment. CONCLUSION: While the receipt of a diagnosis, referral and treatment for depression were uncommon, they seemed to be appropriately targeted. Socio-economic deprivation was not associated with treatment.
OBJECTIF: Décrire la réception d'un diagnostic, de l'orientation et du traitement pour la dépression chez les personnes recevant un traitement antirétroviral (ART), présentant des symptômes dépressifs et fréquentant des cliniques de soins primaires en Afrique du Sud, et étudier les facteurs associés à la réception de ces éléments de soins. MÉTHODES: Il s'agit ici d'une analyse secondaire des données d'un essai contrôlé randomisé d'une intervention destinée à améliorer la détection et le traitement de la dépression chez les patients sous ART dans les soins primaires. Dans cette analyse, nous avons combiné les données transversales et longitudinales des bras d'intervention et témoin. En utilisant des modèles de régression et en ajustant la corrélation intra-grappes des résultats, nous avons étudié les associations entre les caractéristiques sociodémographiques, les symptômes dépressifs, le stress, l'invalidité et la stigmatisation, et la réception d'un diagnostic, d'une orientation et d'un traitement pour la dépression. RÉSULTATS: Sur 2.002 participants inscrits, 18% ont déclaré un diagnostic antérieur de dépression par un agent de santé et 10% ont déclaré avoir reçu des conseils d'un agent spécialisé pour la santé mentale. Le diagnostic, l'orientation et le conseil pendant la période de suivi ont été ciblés de manière appropriée, étant indépendamment plus fréquents chez les participants ayant des scores d'inscription plus élevés pour les symptômes dépressifs, le stress ou l'invalidité. Les participants ayant des scores de stigmatisation plus élevés à l'inscription étaient indépendamment moins susceptibles de recevoir des conseils. La privation socioéconomique sévère était courante mais n'était pas associée au traitement. CONCLUSION: Bien que la réception d'un diagnostic, l'orientation et le traitement de la dépression soient rares, ils semblaient bien ciblés. La privation socioéconomique n'était pas associée au traitement.
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Depresión/diagnóstico , Depresión/terapia , Infecciones por VIH/psicología , Atención Primaria de Salud , Derivación y Consulta , Adulto , Antirreumáticos/uso terapéutico , Consejo , Estudios Transversales , Depresión/epidemiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pobreza , Estigma Social , Sudáfrica/epidemiologíaRESUMEN
BACKGROUND: Consumers purchase fresh strawberries all year long. Extending the fruiting season for new strawberry cultivars is a common breeding goal. Understanding the inheritance of repeat fruiting is key to improving breeding efficiency. Several independent research groups using multiple genotypes and analytic approaches have all identified a single genomic region in strawberry associated with repeat fruiting. Markers mapped to this region were used to evaluate breeding parents from the United States Department of Agriculture - Agricultural Research Service (USDA-ARS) strawberry breeding program at Beltsville, Maryland. RESULTS: Markers mapped to repeat fruiting identified once-fruiting genotypes but not repeat-fruiting genotypes. Eleven of twenty-three breeding parents with repeat-fruiting marker profiles were actually once fruiting, indicating at least one additional locus acting epistatically to suppress repeat fruiting. Family segregation ratios could not be predicted reliably by the combined use of parental phenotypes and marker profiles, when using a single-gene model. Expected segregation ratios were calculated for all phenotypic and marker-profile combinations possible from the mapped locus combined with a hypothetical dominant or recessive suppressor locus. Segregation ratios specific to an epistatic suppressor acting on the mapped locus were observed in four families. The segregation ratios for two families were best explained by a dominant suppressor acting on the mapped locus, and, for the other two, by a recessive suppressor. Not all of the observed ratios could be explained by one model or the other, and when multiple families with a common parent were compared, there was no predicted genotype for the common parent that would lead to all of the observed segregation ratios. CONCLUSIONS: Considering all lines of evidence in this study and others, repeat-fruiting in commercial strawberry is controlled primarily by a dominant allele at a single locus, previously mapped by multiple groups. At least two additional genes, one dominant and one recessive, exist that act epistatically to suppress repeat fruiting. Environmental effects and/or incomplete penetrance likely affect phenotype through the suppressor loci, rather than the primary mapped locus. One of the dominant suppressors acts only in the first year, the year the plant is germinated from seed, and not after the plant has experienced a winter.
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Epistasis Genética , Fragaria/genética , Frutas/crecimiento & desarrollo , Fitomejoramiento , Fragaria/crecimiento & desarrollo , Frutas/genética , Genotipo , FenotipoRESUMEN
In this year there is the 40th anniversary of the first publication of plant nitric oxide (NO) emission by Lowell Klepper. In the decades since then numerous milestone discoveries have revealed that NO is a multifunctional molecule in plant cells regulating both plant development and stress responses. Apropos of the anniversary, these authors aim to review and discuss the developments of past concepts in plant NO research related to NO metabolism, NO signaling, NO's action in plant growth and in stress responses and NO's interactions with other reactive compounds. Despite the long-lasting research efforts and the accumulating experimental evidences numerous questions are still needed to be answered, thus future challenges and research directions have also been drawn up.
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Óxido Nítrico/metabolismo , Fenómenos Fisiológicos de las Plantas , Plantas/metabolismo , Nitrato-Reductasa/fisiología , Óxido Nítrico Sintasa/fisiología , Estrés Nitrosativo/fisiología , Desarrollo de la Planta , Reproducción/fisiología , Transducción de Señal/fisiología , Simbiosis/fisiologíaRESUMEN
Frequently present in pancreatic, colorectal and non-small cell lung carcinomas, oncogenic mutant K-Ras must be localised to the plasma membrane (PM) to be functional. Inhibitors of K-Ras PM localisation are therefore putative cancer chemotherapeutics. By screening a microbial extract library in a high content cell-based assay we detected the rare oligomycin class of Streptomyces polyketides as inhibitors of K-Ras PM localisation. Cultivation and fractionation of three unique oligomycin producing Streptomyces strains yielded oligomycins A-E (1-5) and 21-hydroxy-oligomycin A (6), together with the new 21-hydroxy-oligomycin C (7) and 40-hydroxy-oligomycin B (8). Structures for 1-8 were assigned by detailed spectroscopic analysis. Cancer cell viability screening confirmed 1-8 were cytotoxic to human colorectal carcinoma cells (IC50 > 3 µM), and were inhibitors of the ABC transporter efflux pump P-glycoprotein (P-gp), with 5 being comparable in potency to the positive control verapamil. Significantly, oligomycins 1-8 proved to be exceptionally potent inhibitors of K-Ras PM localisation (Emax 0.67-0.75 with an IC50 ~ 1.5-14 nM).
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Membrana Celular/efectos de los fármacos , Membrana Celular/enzimología , Oligomicinas/farmacología , Proteínas ras/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Perros , Relación Dosis-Respuesta a Droga , Humanos , Células de Riñón Canino Madin Darby , Oligomicinas/síntesis química , Oligomicinas/química , Transporte de Proteínas/efectos de los fármacos , Relación Estructura-Actividad , Proteínas ras/antagonistas & inhibidoresRESUMEN
The objective of this study was to determine the effects of rare earth element-enriched yeast (RY) on egg production, coefficient of total tract apparent digestibility (CTTAD), egg quality, excreta gas emission and excreta microbiota of laying hens. A total of 216 ISA brown laying hens of 52 weeks of age were used in a 5-week feeding trial and data were collected every week. Birds were randomly allotted to three dietary treatments each with six replicates and 12 hens per replicate. Each cage (38 cm width × 50 cm length × 40 cm height) contained one hen. Treatments consisted of corn-soya bean meal-based diet supplemented with 0, 500 or 1000 mg/kg of RY. From weeks 55 to 56, inclusion of RY linearly increased (p < 0.05) egg production. The CTTAD of nitrogen was increased (linear, p < 0.05) with increasing dietary level of RY. In week 55, yolk height and Haugh units were increased linearly (p < 0.05) with increasing dietary RY content. However, no significant effects were observed in terms of excreta emissions and excreta microbiota in laying hens. In conclusion, dietary supplementation with RY improved egg production and CTTAD of nitrogen and slightly improved egg quality in laying hens of the late period of peak egg production.
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Cerio/metabolismo , Pollos , Huevos/normas , Lantano/metabolismo , Oviposición/fisiología , Pichia/química , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Cerio/administración & dosificación , Cerio/química , Dieta/veterinaria , Digestión/efectos de los fármacos , Femenino , Lantano/administración & dosificación , Lantano/química , Pichia/metabolismoRESUMEN
We combine resonant inelastic x-ray scattering and model calculations in the Kondo lattice compound YbInCu_{4}, a system characterized by a dramatic increase in Kondo temperature and associated valence fluctuations below a first-order valence transition at T≃42 K. The bulk-sensitive, element-specific, and valence-projected charge excitation spectra reveal an unusual quasigap in the Yb-derived state density which drives an instability of the electronic structure and renormalizes the low-energy effective Hamiltonian at the transition. Our results provide long-sought experimental evidence for a link between temperature-driven changes in the low-energy Kondo scale and the higher-energy electronic structure of this system.
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PURPOSE: We explored survivors' experiences of chronic bowel symptoms following pelvic radiotherapy, strategies employed in living with these symptoms, effects on daily activities, and roles at home and in the workplace. METHODS: Semi-structured interviews were conducted with 28 individuals (10 gynaecological, 14 prostate, four anal/rectal cancer survivors) who had completed pelvic radiotherapy at least six months prior to data collection and who had experience of bowel symptoms during this post-treatment period. Reflexive thematic analysis was undertaken. RESULTS: We propose four themes describing a process leading from experience of symptoms to withdrawal from activities and roles. These are (1) losing control (the experience of unintended anal leakage or discharge); (2) experiencing embarrassment and fear (the experience of embarrassment or fear of embarrassment as a result of discharge becoming public); (3) managing and reacting (acting to reduce the likelihood of discharge or to prevent this becoming public); and (4) restriction and withdrawal (avoiding specific activities or situations so as to reduce or remove the risk of embarrassment). Returning to the workplace presented additional challenges across these themes. CONCLUSIONS: Impacts of chronic bowel symptoms can be severe. Survivors employ a variety of methods and strategies in living with their symptoms. Some of these support continued role fulfilment but some constitute a withdrawal from pre-treatment roles. Current healthcare provision and statutory protections fail to fully meet needs following pelvic radiotherapy. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to develop and implement evidence-based services and supported self-management programmes for survivors experiencing chronic bowel problems post-radiotherapy.
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An electrochemical approach to directly measure the dynamic process of H2 O2 release from cultures of Arabidopsis thaliana cells is reported. This approach is based on H2 O2 oxidation on a Pt electrode in conjunction with continuous measurement of sample pH. For [H2 O2 ] <1 mm, calibration plots were linear and the amperometric response of the electrode was maximum at pH 6. At higher concentrations ([H2 O2 ] >1 mm), the amperometric response can be described by Michaelian-type kinetics and a mathematical expression relating current intensity and pH was obtained to quantitatively determine H2 O2 concentration. At pH 5.5, the detection limit of the sensor was 3.1 µm (S/N = 3), with a response sensitivity of 0.16 Am(-1 ) cm(-2) and reproducibility was within 6.1% in the range 1-5 × 10(-3 ) m (n = 5). Cell suspensions under normal physiological conditions had a pH between 5.5-5.7 and H2 O2 concentrations in the range 7.0-20.5 µm (n = 5). The addition of exogenous H2 O2 , as well as other potential stress stimuli, was made to the cells and the change in H2 O2 concentration was monitored. This real-time quantitative H2 O2 analysis is a potential marker for the evaluation of oxidative stress in plant cell cultures.
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Arabidopsis/metabolismo , Técnicas Electroquímicas/instrumentación , Peróxido de Hidrógeno/análisis , Estrés Oxidativo , Arabidopsis/fisiología , Biomarcadores/metabolismo , Calibración , Catalasa , Técnicas de Cultivo de Célula , Técnicas Electroquímicas/métodos , Electrodos , Fertilizantes , Peróxido de Hidrógeno/metabolismo , Peróxido de Hidrógeno/farmacología , Concentración de Iones de Hidrógeno , Insecticidas , Metales , Oxidación-Reducción , Platino (Metal) , Reproducibilidad de los Resultados , Sales (Química) , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
We study Na2IrO3 by angle-resolved photoemission spectroscopy, optics, and band structure calculations in the local-density approximation (LDA). The weak dispersion of the Ir 5d-t(2g) manifold highlights the importance of structural distortions and spin-orbit (SO) coupling in driving the system closer to a Mott transition. We detect an insulating gap Δ(gap)≃340 meV which, at variance with a Slater-type description, is already open at 300 K and does not show significant temperature dependence even across T(N)≃15 K. An LDA analysis with the inclusion of SO and Coulomb repulsion U reveals that, while the prodromes of an underlying insulating state are already found in LDA+SO, the correct gap magnitude can only be reproduced by LDA+SO+U, with U=3 eV. This establishes Na2IrO3 as a novel type of Mott-like correlated insulator in which Coulomb and relativistic effects have to be treated on an equal footing.
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It has been hypothesized that radiation-induced oxidative stress is the mechanism for a wide range of negative impacts on biota living in radioactively contaminated areas around Chernobyl. The present study tests this hypothesis mechanistically, for the first time, by modelling the impacts of radiolysis products within the cell resulting from radiations (low linear energy transfer ß and γ), and dose rates appropriate to current contamination types and densities in the Chernobyl exclusion zone and at Fukushima. At 417 µGy h(-1) (illustrative of the most contaminated areas at Chernobyl), generation of radiolysis products did not significantly impact cellular concentrations of reactive oxygen species, or cellular redox potential. This study does not support the hypothesis that direct oxidizing stress is a mechanism for damage to organisms exposed to chronic radiation at dose rates typical of contaminated environments.
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Antioxidantes/metabolismo , Hígado/patología , Hígado/efectos de la radiación , Radiación Ionizante , Especies Reactivas de Oxígeno/metabolismo , Animales , Aves/metabolismo , Carotenoides/metabolismo , Accidente Nuclear de Chernóbil , Monitoreo del Ambiente/métodos , Transferencia Lineal de Energía , Hígado/metabolismo , Oxidación-Reducción , Estrés Oxidativo , alfa-Tocoferol/metabolismoRESUMEN
AIMS: To evaluate the variance in current UK clinical practice and clinical outcomes for direct percutaneous radiologically inserted gastrostomy (RIG). MATERIALS AND METHODS: A prospective UK multicentre survey of RIG performed between October 2008 and August 2010 was performed through the British Society of Gastrointestinal and Abdominal Radiology (BSGAR). RESULTS: Data from 684 patients were provided by 45 radiologists working at 17 UK centres. Two hundred and sixty-three cases (40%) were performed with loop-retained catheters, and 346 (53%) with balloon-retained devices. Sixty percent of all patients experienced pain in the first 24 h, but settled in the majority thereafter. Early complications, defined as occurring in the first 24 h, included minor bleeding (1%), wound infection (3%), peritonism (2%), and tube misplacement (1%). Late complications, defined as occurring between day 2 and day 30 post-procedure, included mild pain (30%), persisting peritonism (2%), and 30 day mortality of 1% (5/665). Pre-procedural antibiotics or anti-methicillin-resistant Staphylococcus aureus (MRSA) prophylaxis did not affect the rate of wound infection, peritonitis, post-procedural pain, or mortality. Ninety-three percent of cases were performed using gastropexy. Gastropexy decreased post-procedural pain (p < 0.001), but gastropexy-related complications occurred in 5% of patients. However, post-procedure pain increased with the number of gastropexy sutures used (p < 0.001). The use of gastropexy did not affect the overall complication rate or mortality. Post-procedure pain increased significantly as tube size increased (p < 0.001). The use of balloon-retention feeding tubes was associated with more pain than the deployment of loop-retention devices (p < 0.001). CONCLUSION: RIG is a relatively safe procedure with a mortality of 1%, with or without gastropexy. Pain is the commonest complication. The use of gastropexy, fixation dressing or skin sutures, smaller tube sizes, and loop-retention catheters significantly reduced the incidence of pain. There was a gastropexy-related complication rate in 5% of patients. Neither pre-procedural antibiotics nor anti-MRSA prophylaxis affected the rate of wound infection.
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Gastrostomía/métodos , Intubación Gastrointestinal/métodos , Radiografía Intervencional/métodos , Estómago/diagnóstico por imagen , Estómago/cirugía , Cirugía Asistida por Computador/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Profilaxis Antibiótica/métodos , Femenino , Estudios de Seguimiento , Gastropexia/métodos , Gastrostomía/efectos adversos , Gastrostomía/instrumentación , Humanos , Intubación Gastrointestinal/efectos adversos , Intubación Gastrointestinal/instrumentación , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Persona de Mediana Edad , Aptitud Física , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Reino Unido , Adulto JovenRESUMEN
AIMS/HYPOTHESIS: This study used proteomics and biochemical approaches to identify novel glucose-regulated proteins and to unveil their role in pancreatic beta cell function. Translationally controlled tumour protein (TCTP) was identified to be one such protein, and further investigations into its function and regulation were carried out. METHODS: Global protein profiling of beta cell homogenates following glucose stimulation was performed using two-dimensional gel electrophoresis. Proteins were identified by mass spectroscopy analysis. Immunoblotting was used to investigate alterations in TCTP protein levels in response to glucose stimulation or cell stress induced by palmitate. To investigate the biological function of TCTP, immunolocalisation, gene knockdown and overexpression of Tctp (also known as Tpt1) were performed. Apoptosis was measured in Tctp knockdown or Tctp-overexpressing cells. Glucose-stimulated insulin secretion was carried out in Tctp knockdown cells. RESULTS: TCTP was identified as a novel glucose-regulated protein, the level of which is increased at stimulatory glucose concentration. Glucose also induced TCTP dephosphorylation and its partial translocation to the mitochondria and the nucleus. TCTP protein levels were downregulated in response to cell stress induced by palmitate or thapsigargin treatments. Gene knockdown by small interfering RNA led to increased apoptosis, whereas overproduction of TCTP prevented palmitate-induced cell death. CONCLUSIONS/INTERPRETATION: Regulation of TCTP protein levels by glucose is likely to be an important cyto-protective mechanism for pancreatic beta cells against damage caused by hyperglycaemia. In contrast, high concentration of palmitate causes cell stress, reduction in TCTP levels and consequently reduced cell viability. Our results imply that TCTP levels influence the sensitivity of beta cells to apoptosis.
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Biomarcadores de Tumor , Proteínas HSP70 de Choque Térmico , Células Secretoras de Insulina , Proteínas de la Membrana , Animales , Humanos , Ratones , Apoptosis/efectos de los fármacos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Electroforesis en Gel Bidimensional , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Etiquetado Corte-Fin in Situ , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/metabolismo , Focalización Isoeléctrica , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ácidos Palmíticos/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , ARN Interferente Pequeño , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Proteína Tumoral Controlada Traslacionalmente 1RESUMEN
Different sites of plasma membrane attachment may underlie functional differences between isoforms of Ras. Here we show that palmitoylation and farnesylation targets H-ras to lipid rafts and caveolae, but that the interaction of H-ras with these membrane subdomains is dynamic. GTP-loading redistributes H-ras from rafts into bulk plasma membrane by a mechanism that requires the adjacent hypervariable region of H-ras. Release of H-ras-GTP from rafts is necessary for efficient activation of Raf. By contrast, K-ras is located outside rafts irrespective of bound nucleotide. Our studies identify a novel protein determinant that is required for H-ras function, and show that the GTP/GDP state of H-ras determines its lateral segregation on the plasma membrane.
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Guanosina Trifosfato/metabolismo , Microdominios de Membrana/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Animales , Línea Celular , Membrana Celular/metabolismo , Cricetinae , Activación Enzimática , Metabolismo de los Lípidos , Microscopía Inmunoelectrónica , Proteínas Proto-Oncogénicas c-raf/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Recombinantes de Fusión/genéticaRESUMEN
The plasma membrane pits known as caveolae have been implicated both in cholesterol homeostasis and in signal transduction. CavDGV and CavKSY, two dominant-negative amino-terminal truncation mutants of caveolin, the major structural protein of caveolae, significantly inhibited caveola-mediated SV40 infection, and were assayed for effects on Ras function. We find that CavDGV completely blocked Raf activation mediated by H-Ras, but not that mediated by K-Ras. Strikingly, the inhibitory effect of CavDGV on H-Ras signalling was completely reversed by replenishing cell membranes with cholesterol and was mimicked by cyclodextrin treatment, which depletes membrane cholesterol. These results provide a crucial link between the cholesterol-trafficking role of caveolin and its postulated role in signal transduction through cholesterol-rich surface domains. They also provide direct evidence that H-Ras and K-Ras, which are targeted to the plasma membrane by different carboxy-terminal anchors, operate in functionally distinct microdomains of the plasma membrane.
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Caveolinas , Membrana Celular/fisiología , Colesterol/metabolismo , Lípidos de la Membrana/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Eliminación de Secuencia , Células 3T3 , Animales , Caveolina 1 , Línea Celular , Chlorocebus aethiops , Cricetinae , Vectores Genéticos , Proteínas de la Membrana/química , Ratones , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Proteínas Recombinantes/metabolismo , Transducción de Señal , Virus 40 de los Simios , TransfecciónRESUMEN
The results of model calculations using exact diagonalization reveal the orbital character of states associated with different Raman loss peaks in Cu K-edge resonant inelastic x-ray scattering (RIXS) from La2CuO4. The model includes electronic orbitals necessary to highlight the nonlocal Zhang-Rice singlet, charge transfer, and d-d excitations, as well as states with apical oxygen 2p(z) character. The dispersion of these excitations is discussed with prospects for resonant final state wave-function mapping. A good agreement with experiments emphasizes the substantial multiorbital character of RIXS profiles in the energy transfer range 1-6 eV.
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We measured the momentum dependence of magnetic excitations in the model spin-1/2 2D antiferromagnetic insulator Sr2CuO2Cl2 (SCOC). We identify a single-spin-wave feature and a multimagnon continuum, with different polarization dependences. The spin waves display a large (70 meV) dispersion between the zone-boundary points (π, 0) and (π/2, π/2). Employing an extended t-t'-t''-U one-band Hubbard model, we find significant electronic hopping beyond nearest-neighbor Cu ions, indicative of extended magnetic interactions. The spectral line shape at (π, 0) indicates sizable quantum effects in SCOC and probably more generally in the cuprates.
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OBJECTIVE: The aim of this study was to determine whether intra-amniotic (IA) sludge, a sonographic finding of hyperechoic matter in the amniotic fluid close to the internal cervical os, is associated with preterm delivery in patients with cervical cerclage. METHODS: A retrospective cohort study of patients who had undergone McDonald cerclage between January 1997 and December 2004 was conducted. Transvaginal ultrasound examinations had been performed at 14-28 weeks of gestation, and the ultrasound images were assessed by three reviewers (blinded to patient outcome) to determine the presence or absence of IA sludge. The primary outcome studied was the gestational age at delivery. RESULTS: A total of 177 patients who had undergone cervical cerclage, and for whom adequate records were available, were identified. Sixty had sonographic evidence of IA sludge (Group 1) and 117 had absence of IA sludge (Group 2). There was no significant difference in the mean gestational age at delivery between the two groups (36.4 ± 4.0 vs. 36.8 ± 2.9 weeks, P = 0.53), and no statistical difference in the rate of preterm delivery at < 28 (6.7% vs. 1.7%, P = 0.18), < 30 (6.7% vs. 3.4%, P = 0.45), < 32 (8.3% vs. 6.8%, P = 0.77) or < 36 (16.7% vs. 19.7%, P = 0.69) weeks of gestation. CONCLUSION: Intra-amniotic sludge on ultrasound is not associated with an increased risk of preterm delivery in patients with cervical cerclage.
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Líquido Amniótico/diagnóstico por imagen , Cerclaje Cervical/efectos adversos , Cuello del Útero/diagnóstico por imagen , Trabajo de Parto Prematuro/diagnóstico por imagen , Adulto , Líquido Amniótico/fisiología , Cuello del Útero/cirugía , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Trabajo de Parto Prematuro/etiología , Embarazo , Resultado del Embarazo , Estudios Retrospectivos , UltrasonografíaRESUMEN
Recent advice to the general public is to increase intake of fresh fruit and vegetables, a message based on the assumed benefits of the antioxidant content of plant substances. Although there have been numerous studies on the reactive oxide species scavenging of fresh food products, few studies have focused on whether or not compounds in the diet can modulate the levels of nitric oxide (NO). Nitric oxide is a key signalling molecule that controls vasodilation and blood pressure, along with a range of other physiological events. Here, it is shown that commonly used food substances, such as cabbage, broccoli, kidney bean and oranges, all have the capacity to scavenge NO from solution, and therefore can potentially alter the level of NO in humans, with ramifications for the physiological systems that NO regulates. Using spinach, at least one element of the NO scavenging ability was shown to be heat-unstable, although heat-treating of other leaf materials had little effect, showing that NO scavenging will still occur after cooking. It is proposed that the NO scavenging of dietary components needs to be investigated more thoroughly before the full effects of increasing antioxidants through increased intake of fresh fruit and vegetables can truly be understood.