Simultaneous Irradiation of Multiple Brain Metastases with VMAT Technique: Comparison with Radiosurgery

Se estudio la aplicación de la técnica VMAT (Radioterapia de Intensidad Modulada en Arcos) con colimador ´ de 120 laminas, para la implementación de esta técnica como alternativa a la radiocirugía estereotáctica. Para ello se realizaron planes de tratamiento (simulaciones) bajo técnica VMAT, mediante planificación inversa y la posterior verificación (medición) física de los planes a 10 pacientes con múltiples metástasis cerebrales y tumor primario controlado, encontrándose un aceptable índice de conformación para esta modalidad (comparable a los de radiocirugía) en lesiones mayores a 1,5cm, así como dosis de radiación en los órganos sanos por debajo de las dosis límites de tolerancia en todos los casos.It was studied the application of VMAT technique (Volumetric Modulated Arc Therapy) with a multileaf collimator of 120 leafs, for implementation of this technique as an alternative to stereotactic radiosurgery. To achieve this goal, treatment plans (simulations) were made under VMAT technique using inverse planning and furthermore the physical verification of these plans to 10 patients with multiple brain metastases and primary tumor controlled, finding an acceptable conformation index for this modality (comparable to radiosurgery) in lesions with 1,5cm or more. The doses of radiation in the healthy organs were below the tolerance dose in all casesFil: Fajardo Freites, Jesús Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina. Universidad Central de Venezuela; VenezuelaFil: Dávila, J.. Universidad Central de Venezuela; Venezuela. Grupo de Radioterapia Oncológica; Venezuel

Structure and hydration of membranes embedded with voltage-sensing domains.

Despite the growing number of atomic-resolution membrane protein structures, direct structural information about proteins in their native membrane environment is scarce. This problem is particularly relevant in the case of the highly charged S1-S4 voltage-sensing domains responsible for nerve impulses, where interactions with the lipid bilayer are critical for the function of voltage-activated ion channels. Here we use neutron diffraction, solid-state nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics simulations to investigate the structure and hydration of bilayer membranes containing S1-S4 voltage-sensing domains. Our results show that voltage sensors adopt transmembrane orientations and cause a modest reshaping of the surrounding lipid bilayer, and that water molecules intimately interact with the protein within the membrane. These structural findings indicate that voltage sensors have evolved to interact with the lipid membrane while keeping energetic and structural perturbations to a minimum, and that water penetrates the membrane, to hydrate charged residues and shape the transmembrane electric field

Simultaneous Irradiation of Multiple Brain Metastases with VMAT Technique: Comparison with Radiosurgery

Se estudio la aplicación de la técnica VMAT (Radioterapia de Intensidad Modulada en Arcos) con colimador ´ de 120 laminas, para la implementación de esta técnica como alternativa a la radiocirugía estereotáctica. Para ello se realizaron planes de tratamiento (simulaciones) bajo técnica VMAT, mediante planificación inversa y la posterior verificación (medición) física de los planes a 10 pacientes con múltiples metástasis cerebrales y tumor primario controlado, encontrándose un aceptable índice de conformación para esta modalidad (comparable a los de radiocirugía) en lesiones mayores a 1,5cm, así como dosis de radiación en los órganos sanos por debajo de las dosis límites de tolerancia en todos los casos.It was studied the application of VMAT technique (Volumetric Modulated Arc Therapy) with a multileaf collimator of 120 leafs, for implementation of this technique as an alternative to stereotactic radiosurgery. To achieve this goal, treatment plans (simulations) were made under VMAT technique using inverse planning and furthermore the physical verification of these plans to 10 patients with multiple brain metastases and primary tumor controlled, finding an acceptable conformation index for this modality (comparable to radiosurgery) in lesions with 1,5cm or more. The doses of radiation in the healthy organs were below the tolerance dose in all casesFacultad de Ciencias Exacta

Simultaneous Irradiation of Multiple Brain Metastases with VMAT Technique: Comparison with Radiosurgery

Se estudio la aplicación de la técnica VMAT (Radioterapia de Intensidad Modulada en Arcos) con colimador ´ de 120 laminas, para la implementación de esta técnica como alternativa a la radiocirugía estereotáctica. Para ello se realizaron planes de tratamiento (simulaciones) bajo técnica VMAT, mediante planificación inversa y la posterior verificación (medición) física de los planes a 10 pacientes con múltiples metástasis cerebrales y tumor primario controlado, encontrándose un aceptable índice de conformación para esta modalidad (comparable a los de radiocirugía) en lesiones mayores a 1,5cm, así como dosis de radiación en los órganos sanos por debajo de las dosis límites de tolerancia en todos los casos.It was studied the application of VMAT technique (Volumetric Modulated Arc Therapy) with a multileaf collimator of 120 leafs, for implementation of this technique as an alternative to stereotactic radiosurgery. To achieve this goal, treatment plans (simulations) were made under VMAT technique using inverse planning and furthermore the physical verification of these plans to 10 patients with multiple brain metastases and primary tumor controlled, finding an acceptable conformation index for this modality (comparable to radiosurgery) in lesions with 1,5cm or more. The doses of radiation in the healthy organs were below the tolerance dose in all casesFacultad de Ciencias Exacta

Proton-coupled dynamics in lactose permease

Lactose permease of Escherichia coli (LacY) catalyzes symport of a galactopyranoside and an H+ via an alternating access mechanism. The transition from an inward- to an outward-facing conformation of LacY involves sugar-release followed by deprotonation. Because the transition depends intimately upon the dynamics of LacY in a bilayer environment, molecular dynamics (MD) simulations may be the only means of following the accompanying structural changes in atomic detail. Here, we describe MD simulations of wild- type apo LacY in phosphatidylethanolamine (POPE) lipids that features two protonation states of the critical Glu325. While the protonated system displays configurational stability, deprotonation of Glu325 causes significant structural rearrangements that bring into proximity side chains important for H+ translocation and sugar binding and closes the internal cavity. Moreover, protonated LacY in phosphatidylcholine (DMPC) lipids shows that the observed dynamics are lipid-dependent. Together, the simulations describe early dynamics of the inward-to-outward transition of LacY that agree well with experimental data

Separating Instability from Aggregation Propensity in γS-Crystallin Variants

AbstractMolecular dynamics (MD) simulations, circular dichroism (CD), and dynamic light scattering (DLS) measurements were used to investigate the aggregation propensity of the eye-lens protein γS-crystallin. The wild-type protein was investigated along with the cataract-related G18V variant and the symmetry-related G106V variant. The MD simulations suggest that local sequence differences result in dramatic differences in dynamics and hydration between these two apparently similar point mutations. This finding is supported by the experimental measurements, which show that although both variants appear to be mostly folded at room temperature, both display increased aggregation propensity. Although the disease-related G18V variant is not the most strongly destabilized, it aggregates more readily than either the wild-type or the G106V variant. These results indicate that γS-crystallin provides an excellent model system for investigating the role of dynamics and hydration in aggregation by locally unfolded proteins

Specific cation effects at aqueous solution-vapor interfaces: Surfactant-like behavior of Li⁺ revealed by experiments and simulations

It is now well established by numerous experimental and computational studies that the adsorption propensities of inorganic anions conform to the Hofmeister series. The adsorption propensities of inorganic cations, such as the alkali metal cations, have received relatively little attention. Here we use a combination of liquid-jet X-ray photoelectron experiments and molecular dynamics simulations to investigate the behavior of K+ and Li+ ions near the interfaces of their aqueous solutions with halide ions. Both the experiments and the simulations show that Li+ adsorbs to the aqueous solution−vapor interface, while K+ does not. Thus, we provide experimental validation of the “surfactant-like” behavior of Li+ predicted by previous simulation studies. Furthermore, we use our simulations to trace the difference in the adsorption of K+ and Li+ ions to a difference in the resilience of their hydration shells

Allosteric Mechanism of Water Channel Gating by Ca2+–calmodulin

Calmodulin (CaM) is a universal regulatory protein that communicates the presence of calcium to its molecular targets and correspondingly modulates their function. This key signaling protein is important for controlling the activity of hundreds of membrane channels and transporters. However, our understanding of the structural mechanisms driving CaM regulation of full-length membrane proteins has remained elusive. In this study, we determined the pseudo-atomic structure of full-length mammalian aquaporin-0 (AQP0, Bos Taurus) in complex with CaM using electron microscopy to understand how this signaling protein modulates water channel function. Molecular dynamics and functional mutation studies reveal how CaM binding inhibits AQP0 water permeability by allosterically closing the cytoplasmic gate of AQP0. Our mechanistic model provides new insight, only possible in the context of the fully assembled channel, into how CaM regulates multimeric channels by facilitating cooperativity between adjacent subunits