Distinct Modulation of Spontaneous and GABA-Evoked Gating by Flurazepam Shapes Cross-Talk Between Agonist-Free and Liganded GABAA Receptor Activity

GABAA receptors (GABAARs) play a crucial inhibitory role in the CNS. Benzodiazepines (BDZs) are positive modulators of specific subtypes of GABAARs, but the underlying mechanism remains obscure. Early studies demonstrated the major impact of BDZs on binding and more recent investigations indicated gating, but it is unclear which transitions are affected. Moreover, the upregulation of GABAAR spontaneous activity by BDZs indicates their impact on receptor gating but the underlying mechanisms remain unknown. Herein, we investigated the effect of a BDZ (flurazepam) on the spontaneous and GABA-induced activity for wild-type (WT, α1β2γ2) and mutated (at the orthosteric binding site α1F64) GABAARs. Surprisingly, in spite of the localization at the binding site, these mutations increased the spontaneous activity. Flurazepam (FLU) upregulated this activity for mutants and WT receptors to a similar extent by affecting opening/closing transitions. Spontaneous activity affected GABA-evoked currents and is manifested as an overshoot after agonist removal that depended on the modulation by BDZs. We explain the mechanism of this phenomenon as a cross-desensitization of ligand-activated and spontaneously active receptors. Moreover, due to spontaneous activity, FLU-pretreatment and co-application (agonist + FLU) protocols yielded distinct results. We provide also the first evidence that GABAAR may enter the desensitized state in the absence of GABA in a FLU-dependent manner. Based on our data and model simulations, we propose that FLU affects agonist-induced gating by modifying primarily preactivation and desensitization. We conclude that the mechanisms of modulation of spontaneous and ligand-activated GABAAR activity concerns gating but distinct transitions are affected in spontaneous and agonist-evoked activity

Physiological and cell ultrastructure disturbances in wheat seedlings generated by Chenopodium murale hairy root exudate.

Chenopodium murale L. is an invasive weed species significantly interfering with wheat crop. However, the complete nature of its allelopathic influence on crops is not yet fully understood. In the present study, the focus is made on establishing the relation between plant morphophysiological changes and oxidative stress, induced by allelopathic extract. Phytotoxic medium of C. murale hairy root clone R5 reduced the germination rate (24% less than control value) of wheat cv. Nataša seeds, as well as seedling growth, diminishing shoot and root length significantly, decreased total chlorophyll content, and induced abnormal root gravitropism. The R5 treatment caused cellular structural abnormalities, reflecting on the root and leaf cell shape and organization. These abnormalities mostly included the increased number of mitochondria and reorganization of the vacuolar compartment, changes in nucleus shape, and chloroplast organization and distribution. The most significant structural changes were observed in cell wall in the form of amoeboid protrusions and folds leading to its irregular shape. These structural alterations were accompanied by an oxidative stress in tissues of treated wheat seedlings, reflected as increased level of H2O2 and other ROS molecules, an increase of radical scavenging capacity and total phenolic content. Accordingly, the retardation of wheat seedling growth by C. murale allelochemicals may represent a consequence of complex activity involving both cell structure alteration and physiological processes.This is a post-peer-review, pre-copyedit version of an article published in Protoplasma. The final authenticated version is available online at: [http://dx.doi.org/10.1007/s00709-018-1250-0

Specific issues in management of large international research projects in the field of security and defence

This article presents specifi c characteristics of large international research projects in the area of security and defence. It is based on the experience of the authors gathered while managing international research projects realised within 7th EU Framework Programme, European Defence Agency (EDA) programmes etc. The issues of project size, international and research character are described in the article. Specifi c elements that characterise projects in security and defence fi eld are also identifi ed and discussed. Finally selected key factors determining the success of such projects are mentioned

Architecture of Mobile Robotics Platform planned for Intelligent Robotic Porter System - IRPS project

The aim of this paper is to present the Intelligent Robotic Porter System with respect to architecture of Mobile Robotic Platform. The set of requirements for Mobile Robotic Platform was defined and analyzed. Main engineering problems that occurred during the development of Mobile Robotic Platform's architecture were specified and described. Problems were confronted with PIAP's proposed solutions for technical issues at this stage of the project

Effect of Inoculant Emgesal® Flux 5 on the Microstructure of Magnesium Alloy AZ91

This work presents the results of the research of the effect of the inoculant Emgesal Flux 5 on the microstructure of the magnesium alloy AZ91. The concentration of the inoculant was increased in samples in the range from 0.1% to 0.6%. The thermal processes were examined with the use of Derivative and Thermal Analysis (DTA). During the examination, the DTA samplers were preheated up to 180 °C. A particular attention was paid to finding the optimum amount of inoculant, which would cause fragmentation of the microstructure. The concentration of each element was verified by means of a spark spectrometer. In addition, the microstructures of the samples were examined with the use of an optical microscope, and an image analysis with a statistical analysis using the NIS-Elements program were carried out. Those analyses aimed at examining the differences between the grain diameters of phase αMg and eutectic αMg+γ(Mg17Al12) in the prepared samples as well as the average size of each type of grain by way of measuring their perimeters. This paper is an introduction to a further research of grain refinement in magnesium alloys, especially AZ91. Another purpose of this research is to achieve better micro-structure fragmentation of magnesium alloys without the related changes of the chemical composition, which should improve the mechanical properties

Benefit Effect of Low Addition Yttrium on the Phase αMg and eutectic αMg+γ(Mg17Al12) in AZ91 Alloy

This paper presents results of a study of the effect of inoculation of yttrium on the microstructure of AZ91 alloy. The concentration of the inoculant was increased in samples in the range from 0.1% up to 0.6%. The influence of Y on the thermal effects resulting from the phase transformations occurring during the crystallisation at different inoculant concentrations were examined with the use of Derivative and Thermal Analysis (DTA). The microstructures of the samples were examined with the use of an optical microscope; and an image analysis with a statistical analysis were also carried out. Those analyses aimed at examining oh the effect of inoculation of the Y on the differences between the grain diameters of phase αMg and eutectic αMg+γ(Mg17Al12) in the prepared examined material as well as the average size of each type of grain by way of measuring their perimeters

Middle superficial cerebral vein

The microanatomical study presents the anatomy of the middle cerebral vein. On the basis of the anatomical data we distinguished concentric and nonconcentric types of tributories of the middle superficial cerebral vein. The nonconcentric type prevails

Wireless Communication Solution for Distributed Structural Health Monitoring

This paper describes a design of wireless distributed SHM (Structure Health Monitoring) system with a particular emphasis on comparison of wireless communication standards. The presented solution is being deployed in the TULCOEMPA project. Several wireless communication standards are compared, with their benefits, disadvantages and typical areas of application. A choice of proper ISM (Industrial Scientific Medical) band and reasons for use of Wireless Sensor Networks are also discussed. The last part of this paper presents the proposed structure and designed prototype. The chosen architecture of the system and the program algorithm used for communication and measurements are described