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

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

Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

Drug delivery into the brain is impeded by the blood-brain-barrier (BBB) that filters out the vast majority of drugs after systemic administration. In this work, we assessed the transport, uptake and cytotoxicity of promising drug nanocarriers, mesoporous silica nanoparticles (MSNs), in in vitro models of the BBB. RBE4 rat brain endothelial cells and Madin-Darby canine kidney epithelial cells, strain II, were used as BBB models. We studied spherical and rod-shaped MSNs with the following modifications: bare MSNs and MSNs coated with a poly (ethylene glycol)-poly(ethylene imine) (PEG-PEI) block copolymer. In transport studies, MSNs showed low permeability, whereas the results of the cellular uptake studies suggest robust uptake of PEG-PEI-coated MSNs. None of the MSNs showed significant toxic effects in the cell viability studies. While the shape effect was detectable but small, especially in the real-time surface plasmon resonance measurements, coating with PEG-PEI copolymers clearly facilitated the uptake of MSNs. Finally, we evaluated the in vivo detectability of one of the best candidates, i.e. the copolymer-coated rod-shaped MSNs, by two-photon in vivo imaging in the brain vasculature. The particles were clearly detectable after intravenous injection and caused no damage to the BBB. Thus, when properly designed, the uptake of MSNs could potentially be utilized for the delivery of drugs into the brain via transcellular transport

Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

Drug delivery into the brain is impeded by the blood-brain-barrier (BBB) that filters out the vast majority of drugs after systemic administration. In this work, we assessed the transport, uptake and cytotoxicity of promising drug nanocarriers, mesoporous silica nanoparticles (MSNs), in in vitro models of the BBB. RBE4 rat brain endothelial cells and Madin-Darby canine kidney epithelial cells, strain II, were used as BBB models. We studied spherical and rod-shaped MSNs with the following modifications: bare MSNs and MSNs coated with a poly (ethylene glycol)-poly(ethylene imine) (PEG-PEI) block copolymer. In transport studies, MSNs showed low permeability, whereas the results of the cellular uptake studies suggest robust uptake of PEG-PEI-coated MSNs. None of the MSNs showed significant toxic effects in the cell viability studies. While the shape effect was detectable but small, especially in the real-time surface plasmon resonance measurements, coating with PEG-PEI copolymers clearly facilitated the uptake of MSNs. Finally, we evaluated the in vivo detectability of one of the best candidates, i.e. the copolymer-coated rod-shaped MSNs, by two-photon in vivo imaging in the brain vasculature. The particles were clearly detectable after intravenous injection and caused no damage to the BBB. Thus, when properly designed, the uptake of MSNs could potentially be utilized for the delivery of drugs into the brain via transcellular transport.Peer reviewe

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

Peer reviewe

Experimental investigation of surfactants adding effect on the value of the critical heat flux during pool boiling of nanofluids

The influence of different surfactants on the pool boiling of water and water-based nanofluid was experimentally investigated. The concentrations of xanthan gum and polyacrylamide, which were used as surfactants, were varied from 10 mg/l to 200 mg/l. The concentration of silicon dioxide nanoparticles of 25 nm diameter was equal to 0.1 vol. %. The dependences of the value of the critical heat flux on the concentrations of the surfactants were obtained as a result of the experiments. It was shown, that both xanthan gum and polyacrylamide increase the critical heat flux. The increase in critical heat flux value for water with polyacrylamide relative to the clear water was 61%, and for water with xanthan gum was 32%. The increase in critical heat flux values for nanofluids with polyacrylamide and with xanthan gum relative to the nanofluids without surfactants were 36% and 13%, respectively, and relative to clear water were 263% and 200%, respectively

About rheology of nanofluids

The rheological properties of several tens of nanofluids based on water, ethylene glycol, and engine oil with nanoparticles of various oxides and diamond is studied experimentally. Particle concentrations and their sizes were varied within quite wide range. Tested nanofluids did not contain any dispersants, while the base fluid was Newtonian liquid. It is revealed that in some cases, nanofluids are characterized by non-Newtonian rheological behavior. In the last part of the paper the effect of the nanoparticles on the properties of drilling fluids is discussed

Experimental investigation of pool boiling of water-based AL2O3 nanofluid on a copper cylinder

Saturated boiling of nanofluid on a copper cylinder is experimentally studied. The studied nanofluid were prepared using distilled water and Al2O3 nanoparticles. The volume concentration of the nanoparticles was equal 3 %. Cylinder diameter was equal 25 mm. The time dependence on the excess temperature at different boiling regimes were obtained. It shown increase of heat transfer coefficient under boiling of nanofluid

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