Crystal structure of the wide-spectrum binuclear zinc β-lactamase from Bacteroides fragilis

AbstractBackground: The metallo-β-lactamase from Bacteroides fragilis hydrolyzes a wide range of β-lactam antibiotics, and is not clinically susceptible to any known β-lactamase inhibitors. B. fragilis is associated with post-surgery hospital infections, and there has been a recent report of plasmid-mediated dissemination of the enzyme. Effective inhibitors are therefore urgently needed. Knowledge of the three-dimensional structure will aid in the drug design effort.Results The crystal structure of the enzyme has been determined by using multiwavelength anomalous diffraction at the zinc absorption edge and refined to 1.85 Å resolution. The structure is a four-layer α/β/β/α molecule. The active site, found at the edge of the β sandwich, contains a binuclear zinc center with several novel features. One zinc is tetrahedrally coordinated, the other has a trigonal bipyramidal coordination; a water/hydroxide molecule serves as a ligand for both metals. The residues that coordinate the two zincs are invariant in all metallo-β-lactamases that have been sequenced, except for two conservative replacements. Despite the existence of the pattern for binuclear zinc binding, the reported structure of the Bacillus cereus enzyme contains only a single zinc.Conclusion Structural analysis indicates that affinity for the penta-coordinated zinc can be modulated by neighboring residues, perhaps explaining the absence of the second zinc in the B. cereus structure. Models of bound substrates suggest that the active-site channel can accommodate a wide variety of β-lactams. We propose that the zinc cluster prepares an hydroxide, probably the hydroxide that ligates both zincs, for nucleophilic attack on the carbonyl carbon atom of the β-lactam. The resulting negatively charged tetrahedral intermediate implicated in catalysis is stabilized by an oxyanion hole formed by the side chain of the invariant Asn193 and the tetrahedral zinc

Wrinkling of a bilayer membrane

The buckling of elastic bodies is a common phenomenon in the mechanics of solids. Wrinkling of membranes can often be interpreted as buckling under constraints that prohibit large amplitude deformation. We present a combination of analytic calculations, experiments, and simulations to understand wrinkling patterns generated in a bilayer membrane. The model membrane is composed of a flexible spherical shell that is under tension and that is circumscribed by a stiff, essentially incompressible strip with bending modulus B. When the tension is reduced sufficiently to a value \sigma, the strip forms wrinkles with a uniform wavelength found theoretically and experimentally to be \lambda = 2\pi(B/\sigma)^{1/3}. Defects in this pattern appear for rapid changes in tension. Comparison between experiment and simulation further shows that, with larger reduction of tension, a second generation of wrinkles with longer wavelength appears only when B is sufficiently small.Comment: 9 pages, 5 color figure

Reposicionamiento para destinos turísticos consolidados: el caso de los Cabos, México

Los Cabos is an international destination, in its maturing phase, sustained with three advantages: localization, nature, and touristic infrastructure. In this document it is revised the concepts and studies related with the sun and beach destination; in its context it’s the problems, and it is outline the perspective of this activity. The application of the theory «Life cycle of the touristic destinations», as a descriptive-predictive model, helps to plan some proposals for a possible replanting of the model.Los Cabos es un destino internacional, en fase de madurez, sustentado en tres ventajas: localización, naturaleza e infraestructura turística. En este documento se revisan los conceptos y estudios relacionados con los destinos de sol y playa; se contextualiza la problemáticay se esbozan las perspectivas de esta actividad, ya que de continuar el actual modelo la competitividad del destino se ve amenazada. La aplicación de la teoría del «Ciclo de vida de los destinos turísticos», como modelo descriptivo-predictivo, ayuda a plantear algunas propuestaspara un posible replanteamiento del modelo

VOCs and PM listing of Eucalyptus globulus combustion in residential wood stoves

Pollutant residential emissions from wood stoves have significant impacts both on the environment and people's health. The above makes it essential to know the types of volatile organic compounds emitted during combustion and explore their relationship with particulate matter and greenhouse gas emissions. This paper studies and analyzes these emissions using Eucalyptus globulus as fuel varying its moisture levels. Emissions were determined using an adapted commercial stove. The concentration levels of volatile organic compounds and particulate matter increase with the moisture of wood. When analyzing volatile organic compounds, particulate matter, and O2 with the combustion stages of wood, it is found that their concentrations were higher in the ignition and the reload stage. The concentrations of CO2 and NOx were higher in the reload stage. Other chemical compounds, such as toluene, xylene, and benzene, were also found within the volatile organic compounds listing, which increased their concentration in the ignition and stable reload stages. However, in the quenching stage, they are not present. Finally, the dispersion of these molecules in the environment is evaluated, obtaining that if the atmospheric conditions are adverse, these molecules remain in the environment in direct contact with the people living in those places

Modelo gerencial de la empresa exportadora colombiana: análisis de decisiones, estrategia y geoconocimiento

The article discusses the concept of management exporting model of Colombian companies. Colombian business break in into different countries, under the concept and scenario of the multi-latins has evidence in perspective the character and qualifications of international business management in the country. It is important to present the scope of the overall international business management and review the proactive nature of the multilatin concept in the framework of management to finally set the parameters of the Colombian exporting management model. Decision making, the strategic framework and broad Geo-knowledge standout.El artículo analiza la concepción del modelo gerencial exportador de las empresas colombianas. La incursión empresarial colombiana en diferentes países, en el marco del concepto y escenario de las multilatinas, ha dejado en perspectiva el carácter y la cualificación de la gerencia empresarial internacional del país. Es importante exponer el alcance de la gerencia empresarial internacional global y revisar el carácter propositivo del concepto “multilatino” en el marco de la gerencia para, finalmente, establecer los parámetros del modelo gerencial exportador colombiano. Se destacan la toma de decisiones, el marco estratégico y el amplio geoconocimiento

MOOSE: Manned On-Orbit Servicing Equipment

The ability to service satellites has thus far been limited to low earth orbit platforms within reach of the Space Shuttle. Other orbits, such as geosynchronous orbits containing high-value spacecraft have not been attainable by a servicing vehicle. The useful life of a satellite can be extended by replacing spent propellant and damaged orbital replacement units, forestalling the need for eventual replacement. This growing need for satellite on-orbits servicing can be met by the Manned On-Orbit Servicing Equipment (MOOSE). Missions requiring orbit transfer capability, precision manipulation and maneuvering, and man-in-the-loop control can be accomplished using MOOSE. MOOSE is a flexible, reusable, single operator, aerobraking spacecraft designed to refuel, repair, and service orbiting spacecraft. MOOSE will be deployed from Space Station Freedom, (SSF), where it will be stored, resupplied, and refurbished

Annexin-A5 assembled into two-dimensional arrays promotes cell membrane repair

Eukaryotic cells possess a universal repair machinery that ensures rapid resealing of plasma membrane disruptions. Before resealing, the torn membrane is submitted to considerable tension, which functions to expand the disruption. Here we show that annexin-A5 (AnxA5), a protein that self-assembles into two-dimensional (2D) arrays on membranes upon Ca2+ activation, promotes membrane repair. Compared with wild-type mouse perivascular cells, AnxA5-null cells exhibit a severe membrane repair defect. Membrane repair in AnxA5-null cells is rescued by addition of AnxA5, which binds exclusively to disrupted membrane areas. In contrast, an AnxA5 mutant that lacks the ability of forming 2D arrays is unable to promote membrane repair. We propose that AnxA5 participates in a previously unrecognized step of the membrane repair process: triggered by the local influx of Ca2+, AnxA5 proteins bind to torn membrane edges and form a 2D array, which prevents wound expansion and promotes membrane resealing