The phytocannabinoid Δ9-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum

Background and purpose: The phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV) has been reported to exhibit a diverse pharmacology; here, we investigate functional effects of Delta(9)-THCV, extracted from Cannabis sativa, using electrophysiological techniques to define its mechanism of action in the CNS. Experimental approach: Effects of Delta(9)-THCV and synthetic cannabinoid agents on inhibitory neurotransmission at interneurone-Purkinje cell (IN-PC) synapses were correlated with effects on spontaneous PC output using single-cell and multi-electrode array (MEA) electrophysiological recordings respectively, in mouse cerebellar brain slices in vitro. Key results: The cannabinoid receptor agonist WIN 55,212-2 (WIN55) decreased miniature inhibitory postsynaptic current (mIPSC) frequency at IN-PC synapses. WIN55-induced inhibition was reversed by Delta(9)-THCV, and also by the CB1 receptor antagonist AM251; Delta(9)-THCV or AM251 acted to increase mIPSC frequency beyond basal values. When applied alone, Delta(9)-THCV, AM251 or rimonabant increased mIPSC frequency. Pre-incubation with Delta(9)-THCV blocked WIN55-induced inhibition. In MEA recordings, WIN55 increased PC spike firing rate; Delta(9)-THCV and AM251 acted in the opposite direction to decrease spike firing. The effects of Delta(9)-THCV and WIN55 were attenuated by the GABA(A) receptor antagonist bicuculline methiodide. Conclusions and implications: We show for the first time that Delta(9)-THCV acts as a functional CB1 receptor antagonist in the CNS to modulate inhibitory neurotransmission at IN-PC synapses and spontaneous PC output. Delta(9)-THCV- and AM251-induced increases in mIPSC frequency beyond basal levels were consistent with basal CB1 receptor activity. WIN55-induced increases in PC spike firing rate were consistent with synaptic disinhibition; whilst Delta(9)-THCV-and AM251-induced decreases in spike firing suggest a mechanism of PC inhibition.

Stability and convergence of a new explicit finite-difference approximation for the variable-order nonlinear fractional diffusion equation

In this paper, we consider the variable-order nonlinear fractional diffusion equation View the MathML source where xRα(x,t) is a generalized Riesz fractional derivative of variable order View the MathML source and the nonlinear reaction term f(u,x,t) satisfies the Lipschitz condition |f(u1,x,t)-f(u2,x,t)|less-than-or-equals, slantL|u1-u2|. A new explicit finite-difference approximation is introduced. The convergence and stability of this approximation are proved. Finally, some numerical examples are provided to show that this method is computationally efficient. The proposed method and techniques are applicable to other variable-order nonlinear fractional differential equations.

Optimized multilayer indium-free electrodes for organic photovoltaics

Flexible multilayer electrodes that combine high transparency, high conductivity, and efficient charge extraction have been deposited, characterised and used as the anode in organic solar cells. The anode consists of an AZO/Ag/AZO stack plus a very thin oxide interlayer whose ionization potential is fine-tuned by manipulating its gap state density to optimise charge transfer with the bulk heterojunction active layer consisting of poly(n-3- hexylthiophene-2,5-diyl) and phenyl-C61-butyric acid methyl ester (P3HT:BC61BM). The deposition method for the stack was compatible with the low temperatures required for polymer substrates. Optimisation of the electrode stack was achieved by modelling the optical and electrical properties of the device and a power conversion efficiency of 2.9% under AM1.5 illumination compared to 3.0% with an ITO-only anode and 3.5% for an ITO:PEDOT electrode. Dark I-V reverse bias characteristics indicate very low densities of occupied buffer states close to the HOMO level of the hole conductor, despite observed ionization potential being high enough. Their elimination should raise efficiency to that with ITO:PEDOT.

Inhibition of nuclear protein import by a monoclonal antibody against a novel class of nuclear pore proteins

Nuclear import of proteins is mediated by the nuclear pore complexes in the nuclear envelope and requires the presence of a nuclear localization signal (NLS) on the karyophilic protein. In this paper, we describe studies with a monoclonal antibody, Mab E2, which recognizes a class of nuclear pore proteins of 60-76 kDa with a common phosphorylated epitope on rat nuclear envelopes. The Mab Ea-reactive proteins fractionated with the relatively insoluble pore complex-containing component of the envelope and gave a finely punctate pattern of nuclear staining in immunofluorescence assays. The antibody did not bind to any cytosolic proteins. Mab E2 inhibited the interaction of a simian virus 40 large T antigen NLS peptide with a specific 60-kDa NLS-binding protein from rat nuclear envelopes in photoaffinity labeling experiments. The antibody blocked the nuclear import of NLS-albumin conjugates in an in vitro nuclear transport assay with digitonin-permeabilized cells, but did not affect passive diffusion of a small nonnuclear protein, lysozyme, across the pore. Mab E2 may inhibit protein transport by directly interacting with the 60-kDa NLS-binding protein, thereby blocking signal-mediated nuclear import across the nuclear pore complex. (C) 1994 Academic Press, Inc.

Política de ubicación de centrales nucleares

La cuestión nuclear, tradicionalmente tratada en su vertiente estrictamente tecnológica, tiene también importantes dimensiones de carácter no técnico que están resultando trascendentales en el proceso de aceptación e incorporación de esta tecnología a las estrategias energéticas de la humanidad. Por una parte, los llamados “usos pacíficos” del átomo arrastran el hándicap de haber nacido precedidos por los usos no pacíficos o bélicos con que esta energía se incorporó a nuestra civilización. Ambos usos alternativos permanecen inequívocamente vinculados no sólo a nivel simbólico, sino también en su escala tecnológica. Por otro lado, la energía nuclear fue promocionada en sus inicios como la gran panacea de la abundancia, impregnada de un halo salvador que intentaba borrar su ingrato y catastrófico nacimiento. Y así se presentó como la gran revolución tecnológica de nuestro siglo, de gran complejidad, perfección y sofisticación, haciéndola abordable sólo por unos pocos elegidos.

牛血清白蛋白与Indo-1相互作用的荧光光谱法研究

以牛血清白蛋白(Bovine serum album in,BSA)与荧光探针Indo-1为蛋白质和配体模型,基于Indo-1的荧光强度与BSA的分析浓度间的关系,建立了计算二者相互作用位点数的方法,并利用荧光共振能量转移及各种荧光技术对Indo-1和BSA的相互作用进行了研究.结果表明,Indo-1在BSA中有3个作用位点,这3个作用位点与BSA中的212位色氨酸(Trp 212)间的距离分别为2.93,2.57和2.40 nm;Indo-1通过疏水性作用进入到BSA的3个疏水性空腔.在荧光猝灭实验中,通过M icrolab 500系列进样器和PTI荧光仪的联用实现了荧光强度的自动和实时记录.

A computational modelling framework to predict macroscopic phenomena in solder joint formation

A computational model of solder joint formation and the subsequent cooling behaviour is described. Given the rapid changes in the technology of printed circuit boards, there is a requirement for comprehensive models of solder joint formation which permit detailed analysis of design and optimization options. Solder joint formation is complex, involving a range of interacting phenomena. This paper describes a model implementation (as part of a more comprehensive framework) to describe the shape formation (conditioned by surface tension), heat transfer, phase change and the development of elastoviscoplastic stress. The computational modelling framework is based upon mixed finite element and finite volume procedures, and has unstructured meshes enabling arbitrarily complex geometries to be analysed. Initial results for both through-hole and surface-mount geometries are presented.

Prevalencia de patologías osteomusculares del miembro superior y su relación con factores ocupacionales en trabajadores de una empresa de flores. Bogotá 2015

Antecedentes: Las patologías osteomusculares del miembro superior son una importante causa de morbilidad laboral a nivel mundial y en nuestro país, particularmente en el sector de la floricultura. Del desarrollo de estos desórdenes se derivan importantes costos derivados del ausentismo laboral, incapacidades y secuelas. Objetivo: determinar la prevalencia de patología osteomuscular de miembro superior con calificación de origen de enfermedad laboral, en los trabajadores con diagnóstico de patología musculo esquelética de miembro superior y su relación con algunos factores ocupacionales y demográficos. Metodología: Estudio de corte transversal en el que se revisaron datos secundarios procedentes de una base de datos del servicio de salud ocupacional entre enero y mayo de 2015, correspondiente a 465 operarios (no administrativos) a término indefinido de una empresa floricultora de Bogotá, incluyendo únicamente aquellos trabajadores con patologías osteomusculares de miembro superior, que contaban con la clasificación en el diagnóstico ya sea como enfermedad laboral o enfermedad común y mayores de edad. Se excluyeron 19 trabajadores, quienes habían sido reubicados en nuevos sitios de trabajo y no se contó con la información para determinar su actividad antes de realizar el cambio. Se evaluaron las siguientes variables: sexo, edad, antigüedad y el cargo desempeñados por los operarios. La relación entre variables se realizó con la prueba de chi2 de Pearson. Se midió la magnitud de la asociación por medio de OR con sus respectivos intervalos de confianza del 95%. Resultados: Se incluyó a 373 operarios a término fijo, con una media de edad de 39 años (DE=5.55) y una media de antigüedad en el cargo de 6 años (DE=1.15). El 82.84% correspondió al sexo femenino. La prevalencia de enfermedad laboral osteomuscular de miembro superior fue del 54,4%. En el análisis de relación entre la calificación de la enfermedad, y demás variables (sexo, antigüedad en el cargo, edad, actividad desempeñada, localización de la lesión); se encontró que: estar entre los 40 a 49 años (OR= 1,7; IC-95%:1,12 – 2,79), diagnóstico de síndrome de manguito (OR= 4.45; IC-95%: 2.48 – 8.23) y el síndrome de túnel de carpo (OR= 4.22; IC-95%: 2.45 – 7.41) se asociaron a enfermedad laboral. Conclusiones: La prevalencia de enfermedad laboral de patología osteomuscular de miembro superior en los operarios de un cultivo de flores de la Sabana de Bogotá es del (54,4%). Se encontró una mayor asociación con el síndrome del manguito rotador y enfermedad laboral. No se encontró asociación entre la enfermedad laboral y la actividad desempeñada, el tiempo de exposición, ni con el sexo del trabajador.

Lo que el tiempo se llevó: el pueblo zápara como patrimonio intangible

El proceso de reconocimiento de la cultura de las comunidades záparas de Ecuador y Perú como parte del patrimonio oral e inmaterial de la humanidad es el tema de reflexión de este libro. La autora analiza dos hechos significativos: el fortalecimiento organizativo e identitario del movimiento indígena ecuatoriano, dentro del cual se constituyó política y socialmente la nacionalidad zápara; y la noción tradicional de patrimonio cultural, enfocada desde una visión monumentalista, a raíz de la instauración de una nueva categoría de patrimonio intangible por parte de la UNESCO. Las visiones, percepciones y vivencias de las instancias nacionales e internacionales involucradas en la candidatura del pueblo zápara como patrimonio oral e inmaterial de la humanidad, constituyen un escenario único para la reflexión de este proceso.

Interactions between age and apoE genotype on fasting and postprandial triglycerides levels

Objective The influences of genetic determinants on the magnitude of postprandial lipaemia are presently unclear. Here the impact of the common apolipoprotein (apo)E epsilon mutation on the postprandial triglyceride (TG) response is determined, along with an assessment of genotype penetrance according to age, body mass index and gender. Methods and results Healthy adults (n = 251) underwent a postprandial investigation, in which blood samples were taken at regular intervals after a test breakfast (0 min, 49 g fat) and lunch (330 min, 29 g fat) until 480 min after the test breakfast. There was a significant impact of apoE genotype on fasting total cholesterol (TC), (P = 0.027), LDL-cholesterol (LDL-C), (P = 0.008), and %LDL3 (P = 0.001), with higher and lower levels in the E4 and E2 carriers respectively relative to the E3/E3 genotype. Reflective of a higher fasting TG (P = 0.001), a significantly higher area under the curve for the postprandial TG response (TG AUC) was evident in the E4 carriers relative to the E3/E3 group (P = 0.038). In the group as a whole, a significant age × genotype interaction was observed for fasting TC (P = 0.021). In the participants >50 years there was a significant impact of genotype on TC (P = 0.005), LDL-C (P = 0.001) and TAG AUC (P = 0.028). Conclusions It is possible that an exaggerated postprandial lipaemia contributes to the increased coronary heart disease risk associated with carriers of the E4 allele; an effect which is more evident in older adults.

Double-gyroid morphology of a polystyrene-block-poly(ferrocenylethylmethylsilane) diblock copolymer: a route to ordered bicontinuous nanoscale architectures

A polystyrene-block-poly(ferrocenylethylmethylsilane) diblock copolymer, displaying a double-gyroid morphology when self-assembled in the solid state, has been prepared with a PFEMS volume fraction phi(PFMS)=0.39 and a total molecular weight of 64 000 Da by sequential living anionic polymerisation. A block copolymer with a metal-containing block with iron and silicon in the main chain was selected due to its plasma etch resistance compared to the organic block. Self-assembly of the diblock copolymer in the bulk showed a stable, double-gyroid morphology as characterised by TEM. SAXS confirmed that the structure belonged to the Ia3d space group.