The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance

The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing transcription factors that have a role in embryonic development, but are primarily known for modulating energy metabolism, lipid storage, and transport, as well as inflammation and wound healing. Currently, there is no consensus as to the overall combined function of PPARs and why they evolved. We hypothesize that the PPARs had to evolve to integrate lipid storage and burning with the ability to reduce oxidative stress, as energy storage is essential for survival and resistance to injury/infection, but the latter increases oxidative stress and may reduce median survival (functional longevity). In a sense, PPARs may be an evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where the ability to store and burn fat is essential for survival, but is a 'double-edged sword', as fats are potentially highly toxic. Ways in which PPARs may reduce oxidative stress involve modulation of mitochondrial uncoupling protein (UCP) expression (thus reducing reactive oxygen species, ROS), optimising forkhead box class O factor (FOXO) activity (by improving whole body insulin sensitivity) and suppressing NFkB (at the transcriptional level). In light of this, we therefore postulate that inflammation-induced PPAR downregulation engenders many of the signs and symptoms of the metabolic syndrome, which shares many features with the acute phase response (APR) and is the opposite of the phenotype associated with calorie restriction and high FOXO activity. In genetically susceptible individuals (displaying the naturally mildly insulin resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated but natural adipose tissue-related inflammatory signal induced by excessive calories and reduced physical activity, which normally couples energy storage with the ability to mount an immune response. This is further worsened when pancreatic decompensation occurs, resulting in gluco-oxidative stress and lipotoxicity, increased inflammatory insulin resistance and oxidative stress. Reactivating PPARs may restore a metabolic balance and help to adapt the phenotype to a modern lifestyle

Heme oxygenase-1 and carbon monoxide in pulmonary medicine

Heme oxygenase-1 (HO-1), an inducible stress protein, confers cytoprotection against oxidative stress in vitro and in vivo. In addition to its physiological role in heme degradation, HO-1 may influence a number of cellular processes, including growth, inflammation, and apoptosis. By virtue of anti-inflammatory effects, HO-1 limits tissue damage in response to proinflammatory stimuli and prevents allograft rejection after transplantation. The transcriptional upregulation of HO-1 responds to many agents, such as hypoxia, bacterial lipopolysaccharide, and reactive oxygen/nitrogen species. HO-1 and its constitutively expressed isozyme, heme oxygenase-2, catalyze the rate-limiting step in the conversion of heme to its metabolites, bilirubin IXα, ferrous iron, and carbon monoxide (CO). The mechanisms by which HO-1 provides protection most likely involve its enzymatic reaction products. Remarkably, administration of CO at low concentrations can substitute for HO-1 with respect to anti-inflammatory and anti-apoptotic effects, suggesting a role for CO as a key mediator of HO-1 function. Chronic, low-level, exogenous exposure to CO from cigarette smoking contributes to the importance of CO in pulmonary medicine. The implications of the HO-1/CO system in pulmonary diseases will be discussed in this review, with an emphasis on inflammatory states

Assessment of innovation intensity: The case of USA

In the literature, some categories and terms related to technological progress and innovation activity are often considered as synonyms or differences between them are not completely clear. Therefore, the author attempts to distinguish these terms and to link them as well. The measurement and assessment of the innovation intensity is based on the ratio of investment efforts and consequent indicators productivity trends. The better this ratio is, the higher the innovation activity is. I propose two methods based on this approach. The first method supposes the measurement of the innovation intensity via the decomposition of the productivity gain into the factors that generate it. These factors are the dynamics of capital productivity and the capital-labour ratio (in logarithms). Thus, the assessment of the innovation intensity is a part of the productivity gain, which is due to the capital productivity dynamics. The second method is based on the special parameter, which characterizes the investment potential of growth. This potential is the need for investments to increase in productivity of single intensity. Calculations based on US statistics since the early 1960s illustrate the role of the innovation factor in certain quantitative assessments. In general, for the period 1961-2014, about 3/4 of the productivity gain is due to the capital-labour ratio growth, and only. results from the capital productivity growth. In 1981-2000, about a half of the productivity gain was due to the innovation factor. This innovation factor is investments in breakthrough technologies. Furthermore, I found out that for a very long period, the investment rate alone had very little effect on the significant changes in the growth productivity rates. At the same time, from the beginning of the 1980s, a reduction in the relative demand for investment with almost the same investment allowed to stop the threatening tendency of reducing the productivity growth rates. The obtained results can be useful for the development of the Russian investment strategy, because the intensification of innovation activity is a basic condition for expanding investment activity. © 2018 Institute of Economics, Ural Branch of the Russian Academy of Sciences. All rights reserved.Проанализирован понятийный аппарат, относящийся к технологическому прогрессу и инновационной деятельности. Представлена схема взаимосвязей в сферах инноваций и инвестиций, на которой иллюстрируется идея разложения прироста производительности на порождающие его факторы. Рассмотрены методические приемы, касающиеся оценки эффективности инновационной деятельности. Приведены расчеты, выполненные на статистике США с начала 1960-х годов по 2014 год.The research has been supported by the Grant of the Russian Foundation for Basic Research, Project No 16-06-00032

Tax Arrears: Crisis Lessons (Example of the Siberian Federal District)

The article analyzes the dynamics of tax arrears to the budget (according to the Federal Tax Service) across Russia and the Siberian Federal District over 2002—2010. The analysis is carried out based on the absolute and relative indicators. It is shown that the tax burden, with and without the arrears taken into account, in the Siberian Federal District is significantly lower than the analogous parameter across Russia. The effect of individual sectors on the summary figures of tax arrears is studie

THE EU’S COHESION POLICY: LATEST DEVELOPMENTS

An analysis and evaluation are made of the evolutionary processes typical for the current regional policy in the EU. Mechanisms of formation and allocation of resources from the structural funds are described. Particular emphasis is given to the actual cohesion results over the recent years. Characteristic is given of the structural policy in 2000—2006 and the program for 2007—2013. The impact of the global financial and economic crisis of 2008—2009 on the specific parameters and priorities of the EU’s regional policy has been viewe

Gross regional product of Russian regions in last years: Dynamic and spatial configuration

The relation between regional and macroeconomic growth in Russia for the period of 1990-2013 are considered in the paper. The purpose is to estimate this ratio depending on the phase (stage) of development. The hypothesis is that the increase in regional disparities within the post-Soviet period picked up by standard measures and noted in the literature, is not associated with the systemic removal of regional indicators from each other. The specific forms of convergence-divergence are typical for the Russian regional space and they have to be identified. The dynamics of regional space configuration in Russia is considered from a new perspective - as a mass distribution of the gross domestic product of regions by the value of growth rates. The estimation and forecast of the structural characteristics of the gross regional product (GRP) mass distribution are made on the basis of the "distribution dynamics" approach up to 2025. The average annual growth in 2025 is expected at around 104.5 %, while growth differentiation significantly increases. The phase of macroeconomic growth for the last 15 years is reflected in its regional components. The GRP growth in Russia in general, both before and after the crisis of 2009, forms a more dense distribution than in 2009. The general trend of the 2000th and subsequent years is characterized by a certain decline in per capita GRP differentiation in relation to the main regional space (74 regions). The results of this paper may be useful for regional regulation policy purposes. A set of the Russian regions in the years of 2009-2013, against to the dominant tendency, provides a dynamics, that can be compared to the number of countries with a developed market. There is an urgent need to create a special research project to study this phenomenon.Рассмотрены вопросы соотношения макроэкономического роста и его региональных составляющих за период 1990-2013 годов. Представлены этапы развития и характер региональной дифференциации. Проведена оценка и прогноз структурных характеристик распределения массы валового продукта регионов России.The article has been prepared with the support of the Russian Foundation for Humanities, the project. 15-02-00198