Gating-induced large aqueous volumetric remodeling and aspartate tolerance in the voltage sensor domain of Shaker K+ channels

Indexación: Scopus.ACKNOWLEDGMENTS. We thank Chris Lingle and Yu Zhou (Washington University) for critical reading of the manuscript and Victoria Prado for Xenopus care and oocyte preparation. We also thank Millennium Scientific Initiative P029-022-F. This work was supported by Fondecyt Postdoctoral Grants 3170599 (to I.D.-F.) and 3160321 (to H.M.).Neurons encode electrical signals with critically tuned voltage-gated ion channels and enzymes. Dedicated voltage sensor domains (VSDs) in these membrane proteins activate coordinately with an unresolved structural change. Such change conveys the transmembrane translocation of four positively charged arginine side chains, the voltage-sensing residues (VSRs; R1–R4). Countercharges and lipid phosphohead groups likely stabilize these VSRs within the low-dielectric core of the protein. However, the role of hydration, a sign-independent charge stabilizer, remains unclear. We replaced all VSRs and their neighboring residues with negatively charged aspartates in a voltage-gated potassium channel. The ensuing mild functional effects indicate that hydration is also important in VSR stabilization. The voltage dependency of the VSR aspartate variants approached the expected arithmetic summation of charges at VSR positions, as if negative and positive side chains faced similar pathways. In contrast, aspartates introduced between R2 and R3 did not affect voltage dependence as if the side chains moved outside the electric field or together with it, undergoing a large displacement and volumetric remodeling. Accordingly, VSR performed osmotic work at both internal and external aqueous interfaces. Individual VSR contributions to volumetric works approached arithmetical additivity but were largely dissimilar. While R1 and R4 displaced small volumes, R2 and R3 volumetric works were massive and vectorially opposed, favoring large aqueous remodeling during VSD activation. These diverse volumetric works are, at least for R2 and R3, not compatible with VSR translocation across a unique stationary charge transfer center. Instead, VSRs may follow separated pathways across a fluctuating low-dielectric septum. © National Academy of Sciences. All rights reserved.https://www.pnas.org/content/115/32/820

Pore dimensions and the role of occupancy in unitary conductance of Shaker K channels

Indexación: Web of Science; Scopus.K channels mediate the selective passage of K+ across the plasma membrane by means of intimate interactions with ions at the pore selectivity filter located near the external face. Despite high conservation of the selectivity filter, the K+ transport properties of different K channels vary widely, with the unitary conductance spanning a range of over two orders of magnitude. Mutation of Pro475, a residue located at the cytoplasmic entrance of the pore of the small-intermediate conductance K channel Shaker (Pro475Asp (P475D) or Pro475Gln (P475Q)), increases Shaker's reported. 20-pS conductance by approximately six-and approximately threefold, respectively, without any detectable effect on its selectivity. These findings suggest that the structural determinants underlying the diversity of K channel conductance are distinct from the selectivity filter, making P475D and P475Q excellent probes to identify key determinants of the K channel unitary conductance. By measuring diffusion-limited unitary outward currents after unilateral addition of 2 M sucrose to the internal solution to increase its viscosity, we estimated a pore internal radius of capture of 0.82 for all the three Shaker variants (wild type, P475D, and P475Q). This estimate is consistent with the internal entrance of the Kv1.2/2.1 structure if the effective radius of hydrated K+ is set to 4 A. Unilateral exposure to sucrose allowed us to estimate the internal and external access resistances together with that of the inner pore. We determined that Shaker resistance resides mainly in the inner cavity, whereas only similar to 8% resides in the selectivity filter. To reduce the inner resistance, we introduced additional aspartate residues into the internal vestibule to favor ion occupancy. No aspartate addition raised the maximum unitary conductance, measured at saturating [K+], beyond that of P475D, suggesting an similar to 200-pS conductance ceiling for Shaker. This value is approximately one third of the maximum conductance of the large conductance K (BK) channel (the K channel of highest conductance), reducing the energy gap between their K+ transport rates to similar to 1 kT. Thus, although Shaker's pore sustains ion translocation as the BK channel's does, higher energetic costs of ion stabilization or higher friction with the ion's rigid hydration cage in its narrower aqueous cavity may entail higher resistance.http://jgp.rupress.org/content/146/2/13

Novel InN/InGaN multiple quantum well structures for slow‐light generation at telecommunication wavelengths

The third order susceptibility is responsible for a variety of optical non-linear phenomena -like self focusing, phase conjugation and four-wave mixing- with applications in coherent control of optical communication. InN is particularly attractive due to its near-IR bandgap and predicted high nonlinear effects. Moreover, the synthesis of InN nanostructures makes possible to taylor the absorption edge in the telecomunication spectral range and enhance nonlinear parameters thanks to carrier confinement. In this work, we assess the nonlinear optical behavior of InN/InxGa(1-x)N (0.9 > x > 0.7) multiplequantum-well (MQW) structures grown by plasma-assisted MBE on GaN-on-sapphire templates. Low-temperature (5 K) photoluminescence measurements show near-IR emission whose intensity increases with the In content in the barriers, which is explained in terms of the existence of piezoelectric fields in the structures. The nonlinear optical absorption coefficient, α2, were measured at 1.55 μm using the Z-scan method. We observe a strong dependence of the nonlinear absorption coefficient on the In content in the barriers. Saturable absorption is observed for the sample with x = 0.9, with α2 ̃ -9x103 cm/GW. For this sample, an optically controlled reduction of the speed of light by a factor S ∼ 80 is obtained at 1.55 μm. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA

Las formas de organización de la enseñanza en el policlínico universitario su conceptualización y abordaje.

Las transformaciones que hoy se proponen en la Educación Médica, dada la descentralización de la enseñanza en los municipios, harán posible un abordaje educacional más innovador, apoyado en las tecnologías de la información y la comunicación (TIC), acercando al estudiante al escenario profesional desde el inicio de la Carrera. Todo ello permitirá un equilibrio entre la docencia, la investigación y la asistencia. Como resultado de este rediseño de programas en las Ciencias Médicas, donde el aprendizaje es a nivel del Policlínico Universitario, se ha hecho necesario realizar transformaciones en las Formas de Organización de la Enseñanza (FOE), en la Atención Primaria de Salud. Con el presente trabajo, pretendemos ofrecer nuestros criterios sobre las características de estas FOE, así como brindar elementos metodológicos para la impartición de algunas de ellas, de forma tal que puedan ser utilizadas por igual por el claustro profesoral y poder elevar la calidad del proceso docente.  Palabras clave: Formas de Organización de la Enseñanza (FOE), Policlínico Universitario, Educación Médica, Videoclase, Tecnología Educativa

Nonlinear absorption of InN/InGaN multiple-quantum-well structures at optical telecommunication wavelengths

We report on the nonlinear optical absorption of InN/ InxGa 1-x N (x=0.8,0.9) multiple-quantum-well structures characterized at 1.55 μm by the Z-scan method in order to obtain the effective nonlinear absorption coefficient (α2) of the samples at high repetition rate. Saturable absorption is observed for the sample with x=0.9, with an effective α2 ∼-9× 103 cm/GW for the studied optical regime. For lower In content in the barrier, reverse saturable absorption is observed, which is attributed to two-photon absorption. © 2011 American Institute of Physics.Peer Reviewe

Aspectos esenciales en la elaboración de las videoclases en las ciencias de la salud.

Uno de los recursos de aprendizaje más utilizado en la actualidad en los procesos docentes de las Ciencias de la Salud es la Videoclase. Para afrontar la elaboración de estos medios de enseñanza es vital proveer al profesor de herramientas de apoyo sencillas y flexibles que le permitan lograr sus objetivos pedagógicos, ofreciendo a su alumnado el soporte y apoyo adecuado para cubrir sus necesidades.  Este trabajo brinda una serie de recomendaciones para tratar de unificar los criterios acerca de la elaboración de las Videoclases, así como orientar a los profesores que van a enfrentar este reto dentro del proceso docente.  Se analizan los aspectos fundamentales que deben tenerse en cuenta en el momento de la confección de la Videoclase, así como los procesos comunicacionales que están involucrados y las características y responsabilidades que debe tener un teleprofesor.  Palabras clave: Videoclases, Teleprofesor, Policlínico Universitario, Recursos de aprendizaje, Medios de enseñanza, Tecnología educativa

Non-linear absorption of InN/InGaN multiple-quantum-well structures at optical telecommunication wavelengths

We report on the nonlinear optical absorption of InN/ InxGa1−xN x=0.8, 0.9 multiple-quantum-well structures characterized at 1.55 m by the Z-scan method in order to obtain the effective nonlinear absorption coefficient 2 of the samples at high repetition rate. Saturable absorption is observed for the sample with x=0.9, with an effective 2 −9 103 cm/GW for the studied optical regime. For lower In content in the barrier, reverse saturable absorption is observed, which is attributed to two-photon absorption.Ministerio de Ciencia e InnovaciónComunidad de Madri

α-Glucosidase and α- amylase inhibition potentials of ten wild Mexican species of Verbenaceae

Purpose: To evaluate the inhibitory activity of 10 wild Verbenaceae species from Mexico against α- glucosidase and α-amylase.Methods: Ethanol leaf extracts of 10 Verbenaceae species from Mexico were prepared. The inhibitory activity of the extracts against α-glucosidase and α-amylase was evaluated using enzymatic protocols. At least four serial diluted concentrations of each extract was used to calculate the half-maximal inhibitory concentration (IC50).Results: The 10 evaluated Verbenaceae species showed high α-glucosidase inhibition activity, but a low inhibitory effect on α-amylase. Aloysia gratissima (IC50 = 0.122 mg/mL), Verbena carolina (IC50 = 0.112 mg/mL), Bouchea prismatica (IC50 = 0.122 mg/mL), Verbena menthiflora (IC50 = 0.071mg/mL) and Priva mexicana (IC50 = 0.032 mg/mL) exhibited the strongest inhibitory activities against α- glucosidase.Conclusion: All the Verbenaceae species studied possess α-glucosidase inhibitory effect, with P. mexicana being the one with the strongest activity. These findings demonstrate the highs potential of these species as a source of natural antihyperglycemic agents for type 2 diabetes therapy.Keywords: Hyperglycemic, Diabetes, α-Glucosidase, α-Amylase Verbenaceae, Aloysia gratissima, Bouchea prismatica, Priva mexican

Active School Transport among Children from Canada, Colombia, Finland, South Africa, and the United States: A Tale of Two Journeys

Walking and biking to school represent a source of regular daily physical activity (PA). The objectives of this paper are to determine the associations of distance to school, crime safety, and socioeconomic variables with active school transport (AST) among children from five culturally and socioeconomically different country sites and to describe the main policies related to AST in those country sites. The analytical sample included 2845 children aged 9–11 years from the International Study of Childhood Obesity, Lifestyle and the Environment. Multilevel generalized linear mixed models were used to estimate the associations between distance, safety and socioeconomic variables, and the odds of engaging in AST. Greater distance to school and vehicle ownership were associated with a lower likelihood of engaging in AST in sites in upper-middle- and high-income countries. Crime perception was negatively associated to AST only in sites in high-income countries. Our results suggest that distance to school is a consistent correlate of AST in different contexts. Our findings regarding crime perception support a need vs. choice framework, indicating that AST may be the only commuting choice for many children from the study sites in upper-middle-income countries, despite the high perception of crime

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub