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1.
Radiographics ; 43(5): e220063, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37079461

RESUMEN

Numerous entities, both structural and pathologic, can manifest as a contrast material- or blood-filled cardiac outpouching at imaging. These outpouchings often resemble one another and are frequently unfamiliar to imagers and clinicians, creating uncertainty when detected. Furthermore, the diagnostic criteria for conditions such as hernia, aneurysm, pseudoaneurysm, and diverticulum have not been consistently applied in studies and reports cited in the literature describing these outpouchings, adding to the confusion among general and cardiothoracic imagers. Pouches and outpouchings are commonly found incidentally on thoracic and abdominal CT scans obtained for other reasons. Many pouches and outpouchings can be confidently diagnosed or ignored at routine imaging, whereas others may require further evaluation with electrocardiographically gated CT, cardiac MRI, or echocardiography for a more definitive diagnosis. It is easiest to group and diagnose these entities on the basis of their cardiac chamber location or their involvement with the interatrial and interventricular septa. Ancillary features, such as motion, morphology, neck and body size, presence or absence of thrombus, and late gadolinium enhancement characteristics, are important in reaching a correct diagnosis. The aim of this article is to provide a practical guide to pouches and outpouchings of the heart. Each entity is defined according to its cause, imaging characteristics, clinical significance, and relevant associated findings. Mimics of cardiac pouches and outpouchings such as the Bachmann bundle, atrial veins, and thebesian vessels also are briefly discussed. Quiz questions for this article are available in the supplemental material. ©RSNA, 2023.


Asunto(s)
Medios de Contraste , Gadolinio , Humanos , Corazón , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X
2.
Pacing Clin Electrophysiol ; 46(7): 717-720, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37335091

RESUMEN

BACKGROUND: The use of left bundle branch pacing (LBBP) has dramatically increased since it was first described in 2016, but to date there are no published data on the safety of performing magnetic resonance imaging (MRI) in these patients. METHODS: Patients with LBBP who underwent MRI between January 2016 and October 2022 were retrospectively studied in our clinical center, which has a special program for imaging patients with cardiac devices. All patients underwent close cardiac monitoring throughout the MRI scans. Occurrence of arrhythmias or other adverse effects during MRI were assessed. LBBP lead parameters immediately pre- and post-MRI and at an outpatient follow-up were compared. RESULTS: Fifteen patients with LBBP underwent a total of 19 MRI sessions during the study period. Lead parameters did not significantly change after the MRI or on follow-up, which took place at a median of 91 days after the MRI. No patient developed arrhythmias during the MRI sessions, and no adverse effects such as lead dislodgement were reported. CONCLUSION: Although larger studies are necessary to verify our findings, MRI in patients with LBBP appears safe based on this initial case series.


Asunto(s)
Fascículo Atrioventricular , Bloqueo de Rama , Humanos , Bloqueo de Rama/diagnóstico por imagen , Bloqueo de Rama/terapia , Bloqueo de Rama/etiología , Estimulación Cardíaca Artificial/métodos , Estudios Retrospectivos , Electrocardiografía/métodos , Resultado del Tratamiento
3.
Proc Natl Acad Sci U S A ; 116(47): 23594-23599, 2019 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-31685633

RESUMEN

Fire-prone invasive grasses create novel ecosystem threats by increasing fine-fuel loads and continuity, which can alter fire regimes. While the existence of an invasive grass-fire cycle is well known, evidence of altered fire regimes is typically based on local-scale studies or expert knowledge. Here, we quantify the effects of 12 nonnative, invasive grasses on fire occurrence, size, and frequency across 29 US ecoregions encompassing more than one third of the conterminous United States. These 12 grass species promote fire locally and have extensive spatial records of abundant infestations. We combined agency and satellite fire data with records of abundant grass invasion to test for differences in fire regimes between invaded and nearby "uninvaded" habitat. Additionally, we assessed whether invasive grass presence is a significant predictor of altered fire by modeling fire occurrence, size, and frequency as a function of grass invasion, in addition to anthropogenic and ecological covariates relevant to fire. Eight species showed significantly higher fire-occurrence rates, which more than tripled for Schismus barbatus and Pennisetum ciliare. Six species demonstrated significantly higher mean fire frequency, which more than doubled for Neyraudia reynaudiana and Pennisetum ciliare Grass invasion was significant in fire occurrence and frequency models, but not in fire-size models. The significant differences in fire regimes, coupled with the importance of grass invasion in modeling these differences, suggest that invasive grasses alter US fire regimes at regional scales. As concern about US wildfires grows, accounting for fire-promoting invasive grasses will be imperative for effectively managing ecosystems.


Asunto(s)
Ecosistema , Especies Introducidas , Dispersión de las Plantas , Poaceae , Incendios Forestales , Modelos Teóricos , Especificidad de la Especie , Estados Unidos , Incendios Forestales/estadística & datos numéricos
4.
Sensors (Basel) ; 22(6)2022 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-35336361

RESUMEN

Ireland has a wide variety of farmlands that includes arable fields, grassland, hedgerows, streams, lakes, rivers, and native woodlands. Traditional methods of habitat identification rely on field surveys, which are resource intensive, therefore there is a strong need for digital methods to improve the speed and efficiency of identification and differentiation of farmland habitats. This is challenging because of the large number of subcategories having nearly indistinguishable features within the habitat classes. Heterogeneity among sites within the same habitat class is another problem. Therefore, this research work presents a preliminary technique for accurate farmland classification using stacked ensemble deep convolutional neural networks (DNNs). The proposed approach has been validated on a high-resolution dataset collected using drones. The image samples were manually labelled by the experts in the area before providing them to the DNNs for training purposes. Three pre-trained DNNs customized using the transfer learning approach are used as the base learners. The predicted features derived from the base learners were then used to train a DNN based meta-learner to achieve high classification rates. We analyse the obtained results in terms of convergence rate, confusion matrices, and ROC curves. This is a preliminary work and further research is needed to establish a standard technique.


Asunto(s)
Ecosistema , Redes Neurales de la Computación , Granjas , Irlanda , Curva ROC
5.
Ecol Lett ; 24(8): 1735-1737, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34142422

RESUMEN

When analyzing biotic resistance/diversity-invasibility, including predictors of species richness may result in a false negative correlation between native and non-native richness. However, reanalysis of vegetation surveys shows that the negative effect of native richness is statistically significant whether or not predictors of species richness are included.


Asunto(s)
Biodiversidad , Especies Introducidas , Ecosistema
6.
Ecol Lett ; 23(3): 476-482, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31875651

RESUMEN

The biotic resistance hypothesis predicts that diverse native communities are more resistant to invasion. However, past studies vary in their support for this hypothesis due to an apparent contradiction between experimental studies, which support biotic resistance, and observational studies, which find that native and non-native species richness are positively related at broad scales (small-scale studies are more variable). Here, we present a novel analysis of the biotic resistance hypothesis using 24 456 observations of plant richness spanning four community types and seven ecoregions of the United States. Non-native plant occurrence was negatively related to native plant richness across all community types and ecoregions, although the strength of biotic resistance varied across different ecological, anthropogenic and climatic contexts. Our results strongly support the biotic resistance hypothesis, thus reconciling differences between experimental and observational studies and providing evidence for the shared benefits between invasive species management and native biodiversity conservation.


Asunto(s)
Biodiversidad , Ecosistema , Ecología , Especies Introducidas , Plantas , Estados Unidos
7.
J Environ Manage ; 230: 434-445, 2019 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-30300858

RESUMEN

There is a significant and detailed range of sustainability indicators for Irish agri-food production, but there remain areas where further indicator development or new indicators could prove valuable. This review provides an outline of potential developments in Irish assessment of agricultural sustainability following the latest research and in order to meet policy demands. Recent research findings have suggested means of improved quantitative modelling of greenhouse gas emissions, but additional dietary and soil data may be important for this, especially for the potential inclusion of any soil sequestration. This information could also benefit more detailed modelling of nutrient losses to water. Specific concerns over pesticide and antibiotic use may require additional survey work on the particular locations or types of farms of interest. Biodiversity monitoring could be improved by expanding the range of results-oriented agri-environment schemes or employing remote-sensing habitat monitoring, likely supplemented with targeted field surveys for specific objectives. Farm-level economic sustainability is largely well-covered, but additional data collection may be of benefit to address specific issues such as labour costs. Recent additional surveys on farm-level social sustainability have addressed important social indicators of isolation and access to local services, and could be rolled out on a larger number of farms in the future. Wider societal concerns such as animal welfare, genetically modified materials in foodstuffs and antibiotic resistance have limited indicators currently available, and could also benefit from additional surveys. The breadth and detail required in agri-food sustainability indicators present a significant challenge to survey design and implementation, but many developments can be achieved without additional surveys through the use of remote sensing and geospatial technologies and integration of existing datasets. Despite the important benefits of further developments in Irish sustainability indicators, consideration must also be given to farmer confidentiality and survey fatigue.


Asunto(s)
Agricultura , Agricultura/legislación & jurisprudencia , Animales , Biodiversidad , Granjas , Políticas , Suelo
8.
MAGMA ; 31(6): 747-756, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30043124

RESUMEN

OBJECTIVE: Our aim was to develop and evaluate a motion-weighted reconstruction technique for improved cardiac function assessment in 4D magnetic resonance imaging (MRI). MATERIALS AND METHODS: A flat-topped, two-sided Gaussian kernel was used to weigh k-space data in each target cardiac phase and adjacent two temporal phases during the proposed phase-by-phase reconstruction algorithm. The proposed method (Strategy 3) was used to reconstruct 18 cardiac phases based on data acquired using a previously proposed technique [4D multiphase steady-state imaging with contrast enhancement (MUSIC) technique and its self-gated extension using rotating Cartesian k-space (ROCK-MUSIC) from 12 pediatric patients. As a comparison, the same data set was reconstructed into nine phases using a phase-by-phase method (Strategy 1), 18 phases using view sharing (Strategy 4), and 18 phases using a temporal regularized method (Strategy 2). Regional image sharpness and left ventricle volumetric measurements were used to compare the four reconstructions quantitatively. RESULTS: Strategies 1 and 4 generated significantly sharper images of static structures (P ≤ 0.018) than Strategies 2 and 3 but significantly more blurry (P ≤ 0.021) images of the heart. Left ventricular volumetric measurements from the nine-phase reconstruction (Strategy 1) correlated moderately (r < 0.8) with the 2D cine, whereas the remaining three techniques had a higher correlation (r > 0.9). The computational burden of Strategy 2 was six times that of Strategy 3. CONCLUSION: The proposed method of motion-weighted reconstruction improves temporal resolution in 4D cardiac imaging with a clinically practical workflow.


Asunto(s)
Cardiopatías/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética , Algoritmos , Artefactos , Niño , Preescolar , Medios de Contraste , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Lactante , Recién Nacido , Imagen por Resonancia Cinemagnética , Masculino , Movimiento (Física) , Distribución Normal , Fantasmas de Imagen , Respiración , Estudios Retrospectivos , Factores de Tiempo
9.
Kidney Int ; 92(1): 47-66, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28434822

RESUMEN

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.


Asunto(s)
Medios de Contraste/administración & dosificación , Óxido Ferrosoférrico/administración & dosificación , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Animales , Atlas como Asunto , Preescolar , Medios de Contraste/efectos adversos , Medios de Contraste/farmacocinética , Femenino , Óxido Ferrosoférrico/efectos adversos , Óxido Ferrosoférrico/farmacocinética , Hematínicos/administración & dosificación , Humanos , Riñón/fisiopatología , Imagen por Resonancia Magnética/efectos adversos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Eliminación Renal , Insuficiencia Renal Crónica/fisiopatología , Reproducibilidad de los Resultados
10.
Ecology ; 98(7): 1771-1778, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28444961

RESUMEN

Understanding the biodiversity and ecosystem function relationship can be challenging in species-rich ecosystems. Traditionally, species richness has been relied on heavily to explain changes in ecosystem function across diversity gradients. Diversity-Interactions models can test how ecosystem function is affected by species identity, species interactions, and evenness, in addition to richness. However, in a species-rich system, there may be too many species interactions to allow estimation of each coefficient, and if all interaction coefficients are estimable, they may be devoid of any sensible biological meaning. Parsimonious descriptions using constraints among interaction coefficients have been developed but important variability may still remain unexplained. Here, we extend Diversity-Interactions models to describe the effects of diversity on ecosystem function using a combination of fixed coefficients and random effects. Our approach provides improved standard errors for testing fixed coefficients and incorporates lack-of-fit tests for diversity effects. We illustrate our methods using data from a grassland and a microbial experiment. Our framework considerably reduces the complexities associated with understanding how species interactions contribute to ecosystem function in species-rich ecosystems.


Asunto(s)
Biodiversidad , Ecosistema
11.
Ecol Appl ; 26(8): 2388-2399, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27907256

RESUMEN

Humans have a profound effect on fire regimes by increasing the frequency of ignitions. Although ignition is an integral component of understanding and predicting fire, to date fire models have not been able to isolate the ignition location, leading to inconsistent use of anthropogenic ignition proxies. Here, we identified fire ignitions from the Moderate Resolution Imaging Spectrometer (MODIS) Burned Area Product (2000-2012) to create the first remotely sensed, consistently derived, and regionally comprehensive fire ignition data set for the western United States. We quantified the spatial relationships between several anthropogenic land-use/disturbance features and ignition for ecoregions within the study area and used hierarchical partitioning to test how the anthropogenic predictors of fire ignition vary among ecoregions. The degree to which anthropogenic features predicted ignition varied considerably by ecoregion, with the strongest relationships found in the Marine West Coast Forest and North American Desert ecoregions. Similarly, the contribution of individual anthropogenic predictors varied greatly among ecoregions. Railroad corridors and agricultural presence tended to be the most important predictors of anthropogenic ignition, while population density and roads were generally poor predictors. Although human population has often been used as a proxy for ignitions at global scales, it is less important at regional scales when more specific land uses (e.g., agriculture) can be identified. The variability of ignition predictors among ecoregions suggests that human activities have heterogeneous impacts in altering fire regimes within different vegetation types and geographies.


Asunto(s)
Agricultura , Actividades Humanas , Conservación de los Recursos Naturales , Bosques , Humanos , Estados Unidos
12.
Glob Chang Biol ; 21(6): 2424-38, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25626994

RESUMEN

Current challenges to global food security require sustainable intensification of agriculture through initiatives that include more efficient use of nitrogen (N), increased protein self-sufficiency through homegrown crops, and reduced N losses to the environment. Such challenges were addressed in a continental-scale field experiment conducted over 3 years, in which the amount of total nitrogen yield (Ntot ) and the gain of N yield in mixtures as compared to grass monocultures (Ngainmix ) was quantified from four-species grass-legume stands with greatly varying legume proportions. Stands consisted of monocultures and mixtures of two N2 -fixing legumes and two nonfixing grasses. The amount of Ntot of mixtures was significantly greater (P ≤ 0.05) than that of grass monocultures at the majority of evaluated sites in all 3 years. Ntot and thus Ngainmix increased with increasing legume proportion up to one-third of legumes. With higher legume percentages, Ntot and Ngainmix did not continue to increase. Thus, across sites and years, mixtures with one-third proportion of legumes attained ~95% of the maximum Ntot acquired by any stand and had 57% higher Ntot than grass monocultures. Realized legume proportion in stands and the relative N gain in mixture (Ngainmix /Ntot in mixture) were most severely impaired by minimum site temperature (R = 0.70, P = 0.003 for legume proportion; R = 0.64, P = 0.010 for Ngainmix /Ntot in mixture). Nevertheless, the relative N gain in mixture was not correlated to site productivity (P = 0.500), suggesting that, within climatic restrictions, balanced grass-legume mixtures can benefit from comparable relative gains in N yield across largely differing productivity levels. We conclude that the use of grass-legume mixtures can substantially contribute to resource-efficient agricultural grassland systems over a wide range of productivity levels, implying important savings in N fertilizers and thus greenhouse gas emissions and a considerable potential for climate change mitigation.


Asunto(s)
Fabaceae/metabolismo , Pradera , Nitrógeno/metabolismo , Poaceae/metabolismo , Clima , Europa (Continente) , Fijación del Nitrógeno , Temperatura
13.
J Cardiovasc Magn Reson ; 16: 56, 2014 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-25160814

RESUMEN

BACKGROUND: Although left ventricular cardiac geometric indices such as size and sphericity characterize adverse remodeling and have prognostic value in symptomatic patients, little is known of shape distributions in subclinical populations. We sought to quantify shape variation across a large number of asymptomatic volunteers, and examine differences among sub-cohorts. METHODS: An atlas was constructed comprising 1,991 cardiovascular magnetic resonance (CMR) cases contributed from the Multi-Ethnic Study of Atherosclerosis baseline examination. A mathematical model describing regional wall motion and shape was used to establish a coordinate map registered to the cardiac anatomy. The model was automatically customized to left ventricular contours and anatomical landmarks, corrected for breath-hold mis-registration between image slices. Mathematical techniques were used to characterize global shape distributions, after removal of translations, rotations, and scale due to height. Differences were quantified among ethnicity, sex, smoking, hypertension and diabetes sub-cohorts. RESULTS: The atlas construction process yielded accurate representations of global shape (errors between manual and automatic surface points in 244 validation cases were less than the image pixel size). After correction for height, the dominant shape component was associated with heart size, explaining 32% of the total shape variance at end-diastole and 29% at end-systole. After size, the second dominant shape component was sphericity at end-diastole (13%), and concentricity at end-systole (10%). The resulting shape components distinguished differences due to ethnicity and risk factors with greater statistical power than traditional mass and volume indices. CONCLUSIONS: We have quantified the dominant components of global shape variation in the adult asymptomatic population. The data and results are available at cardiacatlas.org. Shape distributions were principally explained by size, sphericity and concentricity, which are known correlates of adverse outcomes. Atlas-based global shape analysis provides a powerful method for quantifying left ventricular shape differences in asymptomatic populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT00005487.


Asunto(s)
Aterosclerosis/diagnóstico , Ventrículos Cardíacos/patología , Imagen por Resonancia Magnética , Anciano , Anciano de 80 o más Años , Puntos Anatómicos de Referencia , Enfermedades Asintomáticas , Aterosclerosis/etnología , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Atlas como Asunto , Simulación por Computador , Femenino , Marcadores Fiduciales , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Modelos Anatómicos , Modelos Cardiovasculares , Valor Predictivo de las Pruebas , Análisis de Componente Principal , Factores de Riesgo , Estados Unidos/epidemiología , Función Ventricular Izquierda , Remodelación Ventricular
14.
Sci Rep ; 14(1): 10265, 2024 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704461

RESUMEN

In low-diversity productive grasslands, modest changes to plant diversity (richness, composition and relative abundance) may affect multiple ecosystem functions (multifunctionality), including yield. Despite the economic importance of productive grasslands, effects of plant diversity and environmental disturbance on multifunctionality are very rarely quantified. We systematically varied species richness, composition, and relative abundance of grassland ley communities and manipulated water supply (rainfed and drought) to quantify effects of diversity and environmental disturbance on multifunctionality. We then replaced the grassland leys with a monoculture crop to investigate 'follow-on' effects. We measured six agronomy-related ecosystem functions across one or both phases: yield, yield consistency, digestibility and weed suppression (grassland ley phase), legacy effect (effect on follow-on crop yield), and nitrogen fertiliser efficiency (full rotation). Drought reduced most ecosystem functions, although effects were species- and function-specific. Increased plant diversity affected mean performance, and reduced variation, across the six functions (contributing to multifunctional stability). Multifunctionality index values across a wide range of mixture diversity were higher than the best monoculture under both rainfed and drought conditions (transgressive over-performance). Higher-diversity, lower-nitrogen (150N) mixtures had higher multifunctionality than a low-diversity, higher-nitrogen (300N) grass monoculture. Plant diversity in productive grasslands is a practical farm-scale management action to mitigate drought impacts and enhance multifunctionality of grassland-crop rotation systems.


Asunto(s)
Biodiversidad , Productos Agrícolas , Sequías , Productos Agrícolas/crecimiento & desarrollo , Pradera , Ecosistema , Agricultura/métodos
15.
Bioorg Med Chem Lett ; 23(5): 1529-36, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23352267

RESUMEN

The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication. The high degree of conservation in the ATP-binding pockets of these enzymes make them appealing targets for broad-spectrum inhibitor development. A pyrrolopyrimidine scaffold was identified from a pharmacophore-based fragment screen with optimization potential. Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity.


Asunto(s)
Girasa de ADN/metabolismo , Topoisomerasa de ADN IV/antagonistas & inhibidores , Pirimidinas/farmacología , Pirroles/farmacología , Inhibidores de Topoisomerasa II/química , Inhibidores de Topoisomerasa II/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Topoisomerasa de ADN IV/química , Diseño de Fármacos , Modelos Moleculares , Pirimidinas/química , Pirroles/química , Relación Estructura-Actividad
16.
Bioorg Med Chem Lett ; 23(5): 1537-43, 2013 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-23294697

RESUMEN

The structurally related bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as prime candidates for the development of broad spectrum antibacterial agents. However, GyrB/ParE targeting antibacterials with spectrum that encompasses robust Gram-negative pathogens have not yet been reported. Using structure-based inhibitor design, we optimized a novel pyrrolopyrimidine inhibitor series with potent, dual targeting activity against GyrB and ParE. Compounds were discovered with broad antibacterial spectrum, including activity against Pseudomonas aeruginosa, Acinetobacter baumannii and Escherichia coli. Herein we describe the SAR of the pyrrolopyrimidine series as it relates to key structural and electronic features necessary for Gram-negative antibacterial activity.


Asunto(s)
Antibacterianos/farmacología , Girasa de ADN/metabolismo , Topoisomerasa de ADN IV/antagonistas & inhibidores , Pirimidinas/farmacología , Pirroles/farmacología , Inhibidores de Topoisomerasa II/farmacología , Antibacterianos/química , Girasa de ADN/química , Topoisomerasa de ADN IV/química , Diseño de Fármacos , Humanos , Pirimidinas/química , Pirroles/química , Relación Estructura-Actividad , Inhibidores de Topoisomerasa II/química
17.
Antimicrob Agents Chemother ; 55(1): 364-7, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20974866

RESUMEN

Mutations in mprF have been shown to result in reduced susceptibility to daptomycin and other cationic antibacterials. An mprF antisense-inducible plasmid was constructed and used to demonstrate that depletion of mprF can reestablish susceptibility to daptomycin. Inducing antisense to mprF also resulted in increased susceptibility to vancomycin and gentamicin but, paradoxically, decreased susceptibility to oxacillin. These results suggest that mprF mutations that reduce susceptibility to cationic antibacterials result in a gain-of-function phenotype.


Asunto(s)
Antibacterianos/farmacología , Daptomicina/farmacología , Farmacorresistencia Bacteriana/genética , ARN sin Sentido/genética , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Proteínas Bacterianas/genética , Northern Blotting , Gentamicinas/farmacología , Pruebas de Sensibilidad Microbiana , Vancomicina/farmacología
18.
Ecology ; 92(7): 1385-92, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21870611

RESUMEN

Biodiversity is an important determinant of primary productivity in experimental ecosystems. We combine two streams of research on understanding the effects of biodiversity on ecosystem function: quantifying phylogenetic diversity as a predictor of biodiversity effects in species-rich systems and the contribution of pairwise interspecific interactions to ecosystem function. We developed a statistical model that partitions the effect of biodiversity into effects due to community phylogenetic diversity and other community properties (e.g., average pairwise interaction, between- and within-functional-group effects, and so forth). The model provides phylogenetically based species-level explanations of differences in ecosystem response for communities with differing species composition. In two well-known grassland experiments, the model approach provides a parsimonious description of the effects of diversity as being due to the joint effect of the average pairwise statistical interaction and to community phylogenetic diversity. Effects associated with functional groupings of species in communities are largely explained by community phylogenetic diversity. The model approach quantifies a direct link between a measure of the evolutionary diversity of species and their interactive contribution to ecosystem function. It proves a useful tool in developing a mechanistic understanding of variation in ecosystem function.


Asunto(s)
Biodiversidad , Biomasa , Modelos Biológicos , Modelos Estadísticos , Filogenia , Poaceae/genética , Poaceae/clasificación
19.
Phys Rev Lett ; 106(17): 175003, 2011 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-21635041

RESUMEN

The Ω phase of the liquid sodium α-Ω dynamo experiment at New Mexico Institute of Mining and Technology in cooperation with Los Alamos National Laboratory has demonstrated a high toroidal field B(ϕ) that is ≃8×B(r), where B(r) is the radial component of an applied poloidal magnetic field. This enhanced toroidal field is produced by the rotational shear in stable Couette flow within liquid sodium at a magnetic Reynolds number Rm≃120. Small turbulence in stable Taylor-Couette flow is caused by Ekman flow at the end walls, which causes an estimated turbulence energy fraction of (δv/v)(2)∼10(-3).

20.
Bioorg Med Chem Lett ; 21(18): 5171-6, 2011 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-21831637

RESUMEN

Dihydrofolate reductase (DHFR) inhibitors such as trimethoprim (TMP) have long played a significant role in the treatment of bacterial infections. Not surprisingly, after decades of use there is now bacterial resistance to TMP and therefore a need to develop novel antibacterial agents with expanded spectrum including these resistant strains. In this study, we investigated the optimization of 2,4-diamnoquinazolines for antibacterial potency and selectivity. Using structure-based drug design, several 7-aryl-2,4-diaminoquinazolines were discovered that have excellent sub-100 picomolar potency against bacterial DHFR. These compounds have good antibacterial activity especially on gram-positive pathogens including TMP-resistant strains.


Asunto(s)
Antibacterianos/farmacología , Diseño de Fármacos , Inhibidores Enzimáticos/farmacología , Quinazolinas/farmacología , Staphylococcus aureus/efectos de los fármacos , Tetrahidrofolato Deshidrogenasa/metabolismo , Antibacterianos/síntesis química , Antibacterianos/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Quinazolinas/síntesis química , Quinazolinas/química , Estereoisomerismo , Relación Estructura-Actividad
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