Dynamic visualization of membrane-inserted fraction of pHluorin-tagged channels using repetitive acidification technique.

Background Changes in neuronal excitability, synaptic efficacy and generally in cell signaling often result from insertion of key molecules into plasma membrane (PM). Many of the techniques used for monitoring PM insertion lack either spatial or temporal resolution. Results We improved the imaging method based on time-lapse total internal reflection fluorescence (TIRF) microscopy and pHluorin tagging by supplementing it with a repetitive extracellular acidification protocol. We illustrate the applicability of this method by showing that brief activation of NMDA receptors ("chemical LTP") in cultured hippocampal neurons induced a persistent PM insertion of glutamate receptors containing the pHluorin-tagged GluR-A(flip) subunits. Conclusion The repetitive acidification technique provides a more accurate way of monitoring the PM-inserted fraction of fluorescently tagged molecules and offers a good temporal and spatial resolution

Unusually Strong Temperature Dependence of P2X3 Receptor Traffic to the Plasma Membrane

ATP-gated P2X3 receptors are expressed by nociceptive neurons and participate in transduction of pain. Responsiveness of P2X3 receptors is strongly reduced at low temperatures, suggesting a role for these receptors in analgesic effects of cooling. Since sustained responsiveness depends on receptor trafficking to the plasma membrane, we employed total internal reflection fluorescence (TIRF) microscopy to highlight perimembrane pool of DsRed-tagged P2X3 receptors and studied the effects of temperature on perimembrane turnover of P2X3-DsRed. Patch-clamp recordings confirmed membrane expression of functional, rapidly desensitizing P2X3-DsRed receptors. By combining TIRF microscopy with the technique of fluorescence recovery after photobleaching (FRAP), we measured the rate of perimembrane turnover of P2X3-DsRed receptors expressed in hippocampal neurons. At room temperature, the P2X3-DsRed perimembrane turnover as measured by TIRF–FRAP had a time constant of ∼2 min. At 29°C, receptor turnover was strongly accelerated (0.6 min), yielding an extremely high temperature dependence coefficient Q10 ∼4.5. In comparison, AMPA receptor turnover measured with TIRF–FRAP was only moderately sensitive to temperature (Q10 ∼1.5). The traffic inhibitor Brefeldin A selectively decelerated P2X3-DsRed receptor turnover at 29°C, but had no effect at 21°C (Q10 ∼1.0). This indicates that receptor traffic to plasma membrane is the key temperature-sensitive component of P2X3 turnover. The selective inhibitor of the RhoA kinase Y27632 significantly decreased the temperature dependence of P2X3-DsRed receptor turnover (Q10 ∼2.0). In summary, the RhoA kinase-dependent membrane trafficking of P2X3 receptors to plasma membrane has an exceptionally high sensitivity to temperature. These findings suggest an important role of P2X3 receptor turnover in hypothermia-associated analgesia

The mechanisms of inhibition of frog endplate currents with homologous derivatives of the 1,1-dimethyl-3-oxybutyl phosphonic acid

The mode of inhibition of endplate currents by four esters of 1,1-dimethyl-3-oxybutyl phosphonic acid with different lipophilicities and molecule lengths were estimated by mathematical modeling based on previous electrophysiological data supplemented by several experiments with rhythmic stimulation. The aim was to discriminate between their receptor and non-receptor effects. It was shown that all esters have a two-component mechanism of depression: inhibition of the receptor open channel and allosteric modulation of the receptorchannel complex. The ratio of both functional components depends on the length and lipophilicity of the esters. Short and less lipophilic esters mostly act as open channel inhibitors and the rate of inhibition substantially depends on the rate of stimulation, i. e. probability of the receptor-channel opening. As the length of the ester radicals and their lipophilicity increased, these compounds were more active as allosteric receptor inhibitors, probably hindering the function of nAChRs from the lipid annulus. © 2012 Institute of Physiology v.v.i

Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain.

Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2alpha (eukaryotic translation initiation factor 2 subunit alpha) dephosphorylation, significantly reduced KA-induced ER stress and neuronal death in vivo and in vitro. KA-induced rise in intracellular calcium was not affected by Salubrinal. The results show that ER responses are essential parts of excitotoxicity mediated by glutamate receptor activation and that Salubrinal decreases neuronal death in vivo. Inhibition of ER stress by small molecular compounds may be beneficial for treatment of various neuronal injuries and brain disorders

ПАРАДОКСЫ В ПОНИМАНИИ ПРОФЕССИОНАЛЬНЫХ ДЕФОРМАЦИЙ ЛИЧНОСТИ

Today, there is no unambiguous definition of the phenomenon of professional deformation of an individual, which makes it impossible to separate the professional deformation from common errors in work, inadequate education of managers, normal fatigue, workaholism and professional “burnout”. An important feature of professional deformations is their gradual development in the process of activity and unawareness thereof by the employee. The lack of clear qualification requirements in the case when negative qualities are compensated with positive qualities often allowing the employee to perform his duties effectively lead to the fact that the professional deformation is not taken into account by the management. One of the problems of the professional deformation phenomenon is that the professional and personal deformations may not match and even contradict each other. The professional deformation is also developed if there is a mismatch between the education and the requirements of a particular job. The experience in different occupations, in addition to the development of positive qualities of a professional, often contributes to the development of negative qualities, i.e., professional deformations produced by various activities. The paper demonstrates the ambiguous relationship between professional deformations and professional incompetence, inadequate professional and life experience, common errors in professional activities. For every of such “paradoxes” general preventive measures are proposed not to allow these phenomena to escalate into a real professional deformation.Сегодня отсутствует однозначное определение феномена профессиональной деформации личности, что не позволяет отделить эту деформацию от обычных ошибок в работе, недостаточного качественного образования управленческих работников, от обычной усталости, трудоголизма и профессионального «выгорания». Важная особенность профессиональных деформаций - их постепенное формирование в процессе деятельности и недостаточное осознание самим работником. Отсутствие четких квалификационных требований в случае компенсаций негативных качеств позитивными, часто позволяющих работнику эффективно выполнять свои обязанности, приводит к тому, что профессиональные деформации не учитываются руководством. Одна из проблем феномена профессиональной деформации заключается в том, что профессиональные и личностные деформации могут не соответствовать и даже противоречить друг другу. Фактором формирования профессиональной деформации также становится несоответствие полученного образования и требований конкретной работы. Опыт работы в разных видах профессиональной деятельности, помимо развития позитивных качеств профессионала, способствует формированию в том числе и негативных свойств, т.е. профессиональных деформаций, полученных при разных видах деятельности. В статье показана неоднозначная взаимосвязь профессиональных деформаций с профессиональной непригодностью, отсутствием профессионального и жизненного опыта, обычными ошибками в профессиональной деятельности. По каждому такому «парадоксу» предлагаются общие пути профилактики данных явлений и недопущения их перерастания в настоящие профессиональные деформации

Transmembrane Prostatic Acid Phosphatase (TMPAP) Interacts with Snapin and Deficient Mice Develop Prostate Adenocarcinoma

Peer reviewe

The Main Problems of the Existing Systems of Labor Motivation of Civil Servants and the Prospects for Overcoming them

Introduction, Purpose. The research topicality is determined by the lack of systematization of the key problems associated with motivation, encouragement and reward for work that generates not only the decrease of production efficiency in different spheres, but also the increasing of workers dissatisfaction. Accordingly, the aim of the study is to analyze and synthesize the problems of motivating work motivation. And the more specific objectives of our research are focused on: 1) the selection of key subject areas; 2) specific analysis for each problematic direction, in particular, the polymotivation (mngoaspektnosti), lack of professional graphic study (as a basis for a better labor norming), according to the labor and implementation of the principle of fairness in the system of motivation, incentives and rewards for work. Methods.The main method of our research is theoretical and methodological analysis and synthesis of existing domestic and foreign research on the stated issues, supplemented by methods involving analysis, hermeneutics, social cultural and socio-economic implementation context of the principle of equity in different systems of motivation, incentives and rewards for work. Results. The main results (findings) of the study are: 1) the allocation of the most problematic areas analysis of imperfection of many existing motivation systems work, in particular: a) labor polymotivation, often distorting labor motivation, if managers and subordinate lose his labor relationship with the Organization and of the entire society values, dljakotorogo they employ; b) insufficient professional graphic study of the specific work, complicating the development of labor standards, loads of medical and hygiene restrictions, as well as on the relevant remuneration standards; in) ill-founded evaluation system; g) common disregard for the principle of equity in the systems of motivation, or a perverse interpretation. Discussion. We see the future of research in a more specific analysis, synthesis and building a clear typology (System) of the various problems associated with motivation, encouragement and reward for labor, in relation to specific organizations and labor posts. This, in our view, is essential not only to improving the activities in specific organizations, but also a kind of prevention of discontent by the work of individuals and entire communities, as well as prevention and reduction of general discontent at the level of the regions and the country as a whole

PARADOXES IN UNDERSTANDING PROFESSIONAL DEFORMATIONS OF AN INDIVIDUAL

Today, there is no unambiguous definition of the phenomenon of professional deformation of an individual, which makes it impossible to separate the professional deformation from common errors in work, inadequate education of managers, normal fatigue, workaholism and professional “burnout”. An important feature of professional deformations is their gradual development in the process of activity and unawareness thereof by the employee. The lack of clear qualification requirements in the case when negative qualities are compensated with positive qualities often allowing the employee to perform his duties effectively lead to the fact that the professional deformation is not taken into account by the management. One of the problems of the professional deformation phenomenon is that the professional and personal deformations may not match and even contradict each other. The professional deformation is also developed if there is a mismatch between the education and the requirements of a particular job. The experience in different occupations, in addition to the development of positive qualities of a professional, often contributes to the development of negative qualities, i.e., professional deformations produced by various activities. The paper demonstrates the ambiguous relationship between professional deformations and professional incompetence, inadequate professional and life experience, common errors in professional activities. For every of such “paradoxes” general preventive measures are proposed not to allow these phenomena to escalate into a real professional deformation

Numerical simulation of the oil displacement process from a porous medium by nanofluid

Numerical simulation of the oil displacement process from a porous medium by nanofluid was carried out. To describe this process a flow model of two immiscible fluids taking into account the surface tension forces and the wetting angle was used. The simulation results of the penetration of fluid with nanoparticles into a porous medium are obtained using the example of the oil displacement. The nanoparticles addition to the displacing fluid affects the process of oil displacement from porous medium significantly. SiO2 particles with a size of 5 nm were used as nanoparticles. The concentration of nanoparticles ranged from 0 to 1 wt.%. The main reason for the increase in ORF (oil recovery factor) during oil displacement by nanofluid is the improvement of rock wetting

The mechanisms of inhibition of frog endplate currents with homologous derivatives of the 1,1-dimethyl-3-oxybutyl phosphonic acid

The mode of inhibition of endplate currents by four esters of 1,1-dimethyl-3-oxybutyl phosphonic acid with different lipophilicities and molecule lengths were estimated by mathematical modeling based on previous electrophysiological data supplemented by several experiments with rhythmic stimulation. The aim was to discriminate between their receptor and non-receptor effects. It was shown that all esters have a two-component mechanism of depression: inhibition of the receptor open channel and allosteric modulation of the receptorchannel complex. The ratio of both functional components depends on the length and lipophilicity of the esters. Short and less lipophilic esters mostly act as open channel inhibitors and the rate of inhibition substantially depends on the rate of stimulation, i. e. probability of the receptor-channel opening. As the length of the ester radicals and their lipophilicity increased, these compounds were more active as allosteric receptor inhibitors, probably hindering the function of nAChRs from the lipid annulus. © 2012 Institute of Physiology v.v.i