Transcriptomic-wide discovery of direct and indirect HuR RNA targets in activated CD4+ T cells

Due to poor correlation between steady state mRNA levels and protein product, purely transcriptomic profiling methods may miss genes posttranscriptionally regulated by RNA binding proteins (RBPs) and microRNAs (miRNAs). RNA immunoprecipitation (RIP) methods developed to identify in vivo targets of RBPs have greatly elucidated those mRNAs which may be regulated via transcript stability and translation. The RBP HuR (ELAVL1) and family members are major stabilizers of mRNA. Many labs have identified HuR mRNA targets; however, many of these analyses have been performed in cell lines and oftentimes are not independent biological replicates. Little is known about how HuR target mRNAs behave in conditional knock-out models. In the present work, we performed HuR RIP-Seq and RNA-Seq to investigate HuR direct and indirect targets using a novel conditional knock-out model of HuR genetic ablation during CD4+ T activation and Th2 differentiation. Using independent biological replicates, we generated a high coverage RIP-Seq data set (>160 million reads) that was analyzed using bioinformatics methods specifically designed to find direct mRNA targets in RIP-Seq data. Simultaneously, another set of independent biological replicates were sequenced by RNA-Seq (>425 million reads) to identify indirect HuR targets. These direct and indirect targets were combined to determine canonical pathways in CD4+ T cell activation and differentiation for which HuR plays an important role. We show that HuR may regulate genes in multiple canonical pathways involved in T cell activation especially the CD28 family signaling pathway. These data provide insights into potential HuR-regulated genes during T cell activation and immune mechanisms

Cluster Analysis of the Innovative Potential of Russian Regions

One of the main directions of economic development of the Russian Federation is the increasing of the role of innovative production and reorganization of the economic system needed to accelerate the pace of formation of the innovative economy. Despite the tasks set by the strategy of innovative development of the Russian Federation for the period up to 2020, the pace of innovative development of the state economy, and accordingly regional economies, is extremely low, and the share of foreign technologies in production processes exceeds 60%. The reformation of the vision of strategic development of innovation economy in Russia is directly connected with defining the actual level of innovative development of regions and formation of mechanisms for the creation of regional and interregional scientific-technical research and innovation infrastructure, which in the long term will provide the current trends of innovative development. Today, the vast majority of regional economies have a high need for new technologies and the formation of the domestic base of scientific and technical production. The needs of the regions are determined not only by the obsolescence of production bases and technological resources, but also by the growing imbalance between the levels of development of regional economies and their isolation. One of the possible options for strategic management of innovative development is the creation the mechanisms of formation regional and interregional innovation and scientific and technical clusters, and, as a consequence, production clusters. However, in order to apply the advantages of cluster development, it is necessary to study the innovative potential of the subjects of the Russian Federation, which will ensure an effective combination of regional economies. This article presents the results of the cluster analysis of the subjects of the Russian Federation on one of the indicators of the innovative potential of the regional economy, as well as the key trends of innovative development of the subjects of the Russian Federation included in the identified clusters

Activities of the Medical Commission during the Prophylactic Medical Examination of Athletes

Background. Preserving the health of the population, including those involved in sports, is one of the priority directions of the state policy of the Russian Federation. In accordance with the existing legislative and regulatory framework, a system for monitoring the quality and safety of medical care is being implemented in health care institutions, which also applies to medical and physical training services. One of the levels of functioning of such a system is the activity of the medical commission. Intensive training and competitive loads make increased demands on the body and are considered a risk factor for the health of athletes, which serves as the basis for their in-depth medical examination and dispensary observation. Therefore, the primary task of the medical commission during the prophylactic medical examination of athletes is to issue an expert opinion in difficult cases regarding the training and competitive activity of persons with deviations in the state of health.The objective of the research was to study of the activities of the medical commission during the prophylactic medical examination of athletes in the conditions of a medical and physical service on the basis of a scientific analysis of the results of its work for two years.Materials and methods. We studied the medical documentation of athletes who passed the medical commission for two years (2018–2019; n = 82 and n = 81, respectively). The nature of the decisions made and the structure of their reasons were analyzed using the Pearson chi-square test with amendments.Results. The share of positive and negative decisions of the commission, as well as temporary suspension from sports by years, their statistical dependences and the strength of the connection between the results are shown. The stability of the negative conclusions of the commission, as well as the structure of their reasons, was revealed (р ˃ 0.05). At the same time, in the second year of observation, they were more often temporarily suspended from sports due to musculoskeletal system diseases and less often as a result of injuries (p < 0.05).Conclusion. The main regularities of the distribution and formation of expert decisions of the medical commission for the years under study were revealed. The necessity of its activity for the medical and physical training service during the medical examination of athletes is noted, as well as the factors that prevent this are indicated

Compromised Circadian Light Hygiene Delays Sleep and Reduces Wellbeing: Lessons From COVID‑19 Lockdown

Представлены результаты исследования, в результате которого выявлено, что снижение качества циркадной световой гигиены (уменьшение времени пребывания на улице и рост экранного времени) во время социальных ограничений и самоизоляции по поводу эпидемии COVID-19, наблюдавшееся у 60 % популяции, было взаимосвязано со смещением фазы сна на более поздние часы и сопровождалось ухудшением здоровья и благополучия респондентов.A combination of decreased outdoor light exposure with increased screen time increase (over 60 % of population) was linked with deteriorated wellbeing: lower sleep quality, quality of life, and physical activity. Altogether, poorer light hygiene during social restrictions was detrimental for sleep health and wellbeing and were associated with sleep phase (chronotype) delay. As the growing body of evidence, assigning late chronotype as the risk factor for health and wellbeing, has been accumulated, this study highlights the importance of maintaining circadian light hygiene

Reversing non-local transport through a superconductor by electromagnetic excitations

Superconductors connected to normal metallic electrodes at the nanoscale provide a potential source of non-locally entangled electron pairs. Such states would arise from Cooper pairs splitting into two electrons with opposite spins tunnelling into different leads. In an actual system the detection of these processes is hindered by the elastic transmission of individual electrons between the leads, yielding an opposite contribution to the non-local conductance. Here we show that electromagnetic excitations on the superconductor can play an important role in altering the balance between these two processes, leading to a dominance of one upon the other depending on the spatial symmetry of these excitations. These findings allow to understand some intriguing recent experimental results and open the possibility to control non-local transport through a superconductor by an appropriate design of the experimental geometry.Comment: 6 pages, 3 figure

Unusual enhancement of effective magnetic anisotropy with decreasing particle size in maghemite nanoparticles

In magnetic nanoparticles (NPs), the observed increase in the effective magnetic anisotropy Keff with the decrease in particle size D is often interpreted, sometimes unsuccessfully, using the equation Keff = Kb + (6KS/D), where Kb is the bulk-like anisotropy of the core spins and KS is the anisotropy of spins in the surface layer. Here, we test the validity of this relation in γ-Fe2O3 NPs for sizes D from 15 nm to 2.5 nm. The samples include oleic acid-coated NPs with D = 2.5, 3.4, 6.3, and 7.0 nm investigated here, with results on 14 other sizes taken from literature. Keff is determined from the analysis of the frequency dependence of the blocking temperature TB after considering the effects of interparticle interactions on TB. For the γ-Fe2O3 NPs with D \u3c 5 nm, an unusual enhancement of Keff with decreasing D, well above the magnitudes predicted by the above equation, is observed. Instead the variation of Keff vs. D is best described by an extension of the above equation by including Ksh term from spins in a shell of thickness d. Based on this core-shell-surface layer model, the data are fit to the equation Keff = Kb + (6KS/D) + Ksh{[1−(2d/D)]−3−1} with Kb = 1.9 × 105 ergs/cm3, KS = 0.035 ergs/cm2, and Ksh = 1.057 × 104 ergs/cm3 as the contribution of spins in the shell of thickness d = 1.1 nm. Significance of this result is discussed