The relevance of studying the regulation of protein-ligand interactions is due to the emergence of new views on the role of metabolites and their key importance in vital processes. To study the protein-ligand interaction, the AB0 antigen-antibody blood system and the enzyme-substrate system of dehydrogenases were used as a test system, and ethanol was used as an influencing factor. In experiments performed with A and B blood erythrocyte antigens, natural AB0 system antibodies and monoclonal antibodies under the influence of ethanol performed change of the degree of agglutination and the time to onset of erythrocyte agglutination. It was found that ethanol can regulate the enzyme-substrate interactions of dehydrogenases: lactate dehydrogenase (EC 1.1.1.27), glyceraldehyde phosphate dehydrogenase (EC 1.1.1.12), and α-glycerol phosphate dehydrogenase (EC 1.1.1.8). The increase in the activity of studied enzymes under the influence of ethanol in the whole blood hemolysate was 2.5 - 3 times higher than in the isolated medium (with pure enzyme preparations).

Contents Authors................................................................................................................................ 7 Acknowledgements............................................................................................................9 Executive summary ........................................................................................................... 11 1. Introduction....................................................................................................................13 Riccardo Valentini, Pekka Leskinen, Pieter Johannes Verkerk, Gert-Jan Nabuurs, George Safonov and Elena Kulikova 2. State of Russian forests and forestry............................................................................17 Dmitry Zamolodchikov, Anatoly Shvidenko, Sergey Bartalev, Elena Kulikova, Alexander Held, Riccardo Valentini and Marcus Lindner 2.1 Major characteristics of Russian forests..........................................................17 2.2 Natural forest disturbances.............................................................................. 21 2.3 Forest governance and use..............................................................................26 2.4 Ecosystem functions and services of Russia’s forests....................................28 2.5 Key challenges in forest resource management..............................................35 2.6 Key messages.................................................................................................... 38 3. Climate change in Russia – past, present and future................................................. 45 Riccardo Valentini, Dmitry Zamolodchikov, Christopher Reyer, Sergio Noce, Monia Santini and Marcus Lindner 3.1 Observed changes of Russian climate in recent decades.............................. 45 3.2 Climate change scenarios................................................................................48 3.3 Key messages.....................................................................................................51 4. Climate change and Russian forests: impacts, vulnerability and adaptation needs... 53 Christopher Reyer, Marcus Lindner, Dmitry Zamolodchikov, Anatoly Shvidenko, Martin Gutsch and Sergey Bartalev 4.1 Observed impacts of climate change...............................................................53 4.2 Projected impacts.............................................................................................56 4.3 Vulnerability assessment................................................................................. 61 4.4 Adaptation needs............................................................................................. 64 4.5 Key messages....................................................................................................67

5. Climate-Smart Forestry in Russia and potential climate change mitigation benefits.............................................................................................................................. 73 Bas Lerink, Mariana Hassegawa, Alexander Kryshen, Anton Kovalev, Eldar Kurbanov, Gert-Jan Nabuurs, Sergei Moshnikov and Pieter Johannes Verkerk 5.1 Introduction...................................................................................................... 73 5.2 Approach and general scenario assumptions.................................................74 5.3 Case study: Republic of Karelia.......................................................................78 5.4 Case study: Republic of Mari El.......................................................................84 5.5 Case study: Angara macro-district (Krasnoyarsk kray).................................. 91 5.6 Concluding remarks, discussion and implications....................................... 98 5.7 Key messages...................................................................................................101 6. The role of the bioeconomy in climate change mitigation in Russia..................... 105 Pekka Leskinen, Jo Van Brusselen, Mariana Hassegawa, Alexander Alekseev, Natalia Lukina, Olga Rakitova, George Safonov, Elena Kulikova and Mikhail Safonov 6.1 Introduction.................................................................................................... 105 6.2 The bioeconomy concept in Russia...............................................................106 6.3 The link between bioeconomy and climate change mitigation.................. 107 6.4 State of Russian forest industry and potential for bioeconomy................... 111 6.5 Sectoral development and outlook................................................................. 113 6.6 Summary and conclusions: Opportunities and challenges for a bioeconomy in Russia.....................................................................................123 6.7 Key messages...................................................................................................125 7. Conclusions.................................................................................................................. 131 Pekka Leskinen, Jo Van Brusselen, Marcus Lindner, Gert-Jan Nabuurs, Pieter Johannes Verkerk, Natalia Lukina, Sergey Bartalev and Elena Kulikova 7.1 Forest resources............................................................................................... 131 7.2 Climate change impacts, adaptation and mitigation....................................132 7.3 Forest management........................................................................................ 133 7.4 Enabling environment for a bioeconomy......................................................134 7.5 Holistic view.................................................................................................... 135 7.6 Key messages and next steps ........................................................................ 136

Forest ecosystems, their products and services play an important role in achieving ambitious climate change mitigation objectives at the same time requiring profound adaptation to climate change. Forest management schemes to support climate action have to be developed within their regional context but also have to be aligned with national or EU-level climate, forest and sustainability policies. The conference on “Managing forests in the 21st century” is the final conference of the FORMASAM, REFORCE and FOREXCLIM research projects. The conference bringstogether scientific experts on forest management from all over Europe facing very specific management challenges. The aim isto discuss and improve the understanding the role of forests and forest management in the context of climate change. The conference addresses climate change impacts, as well as needs for mitigation and adaptation especially with regard to the following scientific questions: 1. What are the impacts of climate extremes and disturbances? 2. What are the management challenges (and options) for resilient forests? 3. What can we do to increase the contribution of forest management to climate change mitigation?

This is the third book in a series on Medieval Novgorod and its surroundings and deals with a substantial body of animal bones that have been recovered over the last decade. The zooarchaeological evidence is discussed by the editor and a number of English and Russian specialists who dug the site, looking at domestic exploitation of animals, diet, animal husbandry, and butchery practices. Detailed data sets are provided to enable the reader to make comparisons with their own research, but the book is also suitable for those with a more general interest in Medieval Russian archaeology.

Blood groups, erythrocyte antigens, and transfusion are fundamental areas of medicine and are related to many disciplines of science like hematology, immunology, surgery, and genetics. This book is a collection of information related to blood groups and transfusion, and a practical resource for all concerned physicians. The book is divided into two sections. The first section includes chapters on blood transfusion reactions and hemolytic disease of the fetus. The second section includes information for the future perspectives of blood group antigens. This book will be a stepping stone for scientists who are rapidly advancing their science journey.

Cancer cells require exogenous methionine for survival and therefore methionine restriction is a promising avenue for treatment. The basis for methionine dependence in cancer cells is still not entirely clear. While the lack of the methionine salvage enzyme methylthioadenosine phosphorylase (MTAP) is associated with methionine auxotrophy in cancer cells, there are other causes for tumors to require exogenous methionine. Restricting methionine by diet or by enzyme depletion, alone or in combination with certain chemotherapeutics, is a promising antitumor strategy.

This book examines how Russia, the world’s most complicated country, is governed. As it resumes its place at the centre of global affairs, the book explores Russia’s overarching strategies, and how it organizes itself (or not) in policy areas ranging from foreign policy and national security to health care, education, immigration, science, sport, agriculture, the environment and criminal justice. The book also discusses the structures and institutions on which Russia relies in order to deliver its goals in these areas of national life, as well as what’s to be done, in policy terms, to improve the country’s performance in its first post-Soviet century. Edited by Irvin Studin, the book includes contributions from a tremendous list of Russia’s leading thinkers and specialists, including Alexei Kudrin, Vladimir Mau, Alexander Auzan, Simon Kordonsky, Fyodor Lukyanov, Natalia Zubarevich and Andrey Melville.

The development and use of Genetically modified organisms (GMOs) has been a contentios subject for the last three decades. while there has been a number of social science analysis of the issues, this is the first book to assess the role of non-governmental organizations (NGOs) in the debate at such wide geographic scale. The various posiotions, for and against GMOs, particularly with regards to trangenic crops, articulated by NGOs in the debate are dissected, classified and juxtaposed to corresponding campaigns. these are discussed in the context of paradigms, including nature fundamentalism and the organic movement, post-colonialism, food sovereignty, anti-globalism, sustainability and feminism. This book also analyses how NGOs interprete the debate and the persuasive communication tactics. 

 

The Paris Climate Agreement established a new target of combating global warming "well below 2 degrees Celsius". This goal will lead to the transformation and deep decarbonization of world economy aiming at nearly zero carbon emissions soon after 2050. The Northeastern Asian countries (responsible for 40% of global CO2 emissions) have all rechnological, resource and ivnestment potential for decarbonization both domestically and internationally, and can show leadership in this efforts on global scale.

The book provides the first in-depth, multidisciplinary study of reurbanization in Russia's Arctic regions, with a specific focus on new mobility patterns, and the resulting birth of new urban Arctic identities in which newcomers and labor migrants form a rising part. It is an invaluable reference for all those interested in current trends in circumpolar regions, showing how the Arctic is becoming more diverse culturally, but also more integrated into globalized trends in terms of economic development, urban sustainability, and migration.

The piblication provides the key lessons learnt from DDPP project experience on designing long-term pathways of low carbon development for 16 world largest economies. The Paris Climate Agreement requires countries to build their concrete vision of the national low-emission transition, consistent with global climate goals that would widely shared by domestic stakeholders and explicitly articulated with domestic socio-economic priorities. We analyze the experience of USA, France, Germany, Russia, China, India, Indonesia, Japan, UK, Mexico, Canada, Italy, Brazil in projecting the deep decarbonization scenarios for their economies by 2050.

The book presents a brief summary of the scientific research on deep decarbonization of 16 largest economies by 2050.

This report examines the changes happening in Russia ever since the issue of global warming was introduced on the global agenda. Only today, after the planet has experienced a variety of catastrophic natural disasters, have world leaders and decision makers grown more aware of the urgency of the problem. In Russia, where climate changes have been more significant than globally on average, the government has increased its objectives in reducing greenhouse gas emissions and put forward a number of initiatives and green policy measures to achieve more sustainability in the long term. Russia’s target for greenhouse gas emissions in 2030 is set at 70-75 percent of the base level of 1990, according to the new action plan adopted by the Kremlin. Other states also recognize the problem but their positions differ in the way the issue should be solved. India, China, the U.S. and Brazil, all of which are important players analyzed in the report, find it hard to reach common ground in reaching a globally binding agreement. Whether this will be done ultimately depends on the outcome of the Paris climate change conference. The report also considers the state of the Russian climate change movement from the experience of NGO activities in Russia, provides an overview of the development of the Russian green energy sector with specific success stories and analyzes the prospects of renewable energy development in different regions of the country.

This supplementary material contains case studies presenting specific aspects of the DDPP country pathways. They illustrate and complement the cross-cutting analysis included in the 2015 DDPP synthesis report

The Deep Decarbonization Pathways Project (DDPP) is a collaborative global research initiative seeking to understand how individual countries can transition, on a technological, socio-economic and policy “pathway”, to a low-carbon economy consistent with the internationally agreed goal of limiting anthropogenic warming to less than 2 degrees Celsius (2°C). Achieving this goal requires that the world cut global net emissions of greenhouse gases (GHG) so that they approach zero between 2050 and 2075, consistent with the Intergovernmental Panel on Climate Change (IPCC)1 2014 findings that to ensure a better-than-even chance of remaining below a 2°C temperature rise, global annual emissions will need to be reduced 42%–57% by 2050 (relative to 2010), and 73%–107% by 2100. This will entail, more than any other factor, the profound transformation of energy systems through steeply reducing carbon intensity in all sectors of the economy. We call this transition “deep decarbonization” and our products, Deep Decarbonization Pathways (DDPs).

The present volume is the fourth issue of the Yearbook series entitled ‘Evolution’. The title of the present volume is ‘From Big Bang to Nanorobots’. In this way we demonstrate that all phases of evolution and Big History are covered in the articles of the present Yearbook. Several articles also present the forecasts about future development.

The main objective of our Yearbook as well as of the previous issues is the creation of a unified interdisciplinary field of research in which the scientists specializing in different disciplines could work within the framework of unified or similar paradigms, using the common terminology and searching for common rules, tendencies and regularities. At the same time for the formation of such an integrated field one should use all available opportunities: theories, laws and methods. In the present volume, a number of such approaches are used.

The volume consists of four sections: Universal Evolutionary Principles; Biosocial Evolution, Ecological Aspects, and Consciousness; Projects for the Future; In Memoriam.

This Yearbook will be useful both for those who study interdisciplinary macroproblems and for specialists working in focused directions, as well as for those who are interested in evolutionary issues of Cosmology, Biology, History, Anthropology, Economics and other areas of study. More than that, this edition will challenge and excite your vision of your own life and the new discoveries going on around us!

MiRNA isoforms (isomiRs) are single stranded small RNAs originating from the same pri-miRNA hairpin as a result of cleavage by Drosha and Dicer enzymes. Variations at the 5ʹ-end of a miRNA alter the seed region of the molecule, thus affecting the targetome of the miRNA. In this manuscript, we analysed the distribution of miRNA cleavage positions across 31 different cancers using miRNA sequencing data of TCGA project. As a result, we found that the processing positions are not tissue specific and that all miRNAs could be correctly classified as ones exhibiting homogeneous or heterogeneous cleavage at one of the four cleavage sites. In 42% of cases (42 out of 100 miRNAs), we observed imprecise 5ʹ-end Dicer cleavage, while this fraction was only 14% for Drosha (14 out of 99). To the contrary, almost all cleavage sites of 3ʹ-ends (either Drosha or Dicer) were heterogeneous. With the use of only four nucleotides surrounding a 5ʹ-end Dicer cleavage position we built a model which allowed us to distinguish between homogeneous and heterogeneous cleavage with the reliable quality (ROC AUC = 0.68). Finally, we showed the possible applications of the study by the analysis of two 5ʹ-end isoforms originating from the same exogeneous shRNA hairpin. It turned out that the less expressed shRNA variant was functionally active, which led to the increased off-targeting. Thus, the obtained results could be applied to the design of shRNAs whose processing will result in a single 5ʹ-variant.

Recent statistics report that more than 3.7 million new cases of cancer occur in Europe yearly, and the disease accounts for approximately 20% of all deaths. High-throughput screening of cancer cell cultures has dominated the search for novel, effective anticancer therapies in the past decades. Recently, functional assays with patient-derived ex vivo 3D cell culture have gained importance for drug discovery and precision medicine. We recently evaluated the major advancements and needs for the 3D cell culture screening, and concluded that strictly standardized and robust sample preparation is the most desired development. Here we propose an artificial intelligence-guided low-cost 3D cell culture delivery system. It consists of a light microscope, a micromanipulator, a syringe pump, and a controller computer. The system performs morphology-based feature analysis on spheroids and can select uniform sized or shaped spheroids to transfer them between various sample holders. It can select the samples from standard sample holders, including Petri dishes and microwell plates, and then transfer them to a variety of holders up to 384 well plates. The device performs reliable semi- and fully automated spheroid transfer. This results in highly controlled experimental conditions and eliminates non-trivial side effects of sample variability that is a key aspect towards next-generation precision medicine.

For over a decade, neuroimaging and brain stimulation studies have investigated neural mechanisms of third-party punishment, a key instrument for social norms enforcement. However, the neural dynamics underlying these mechanisms are still unclear. Previous electroencephalographic studies on third-party punishment have shown that inter-brain connectivity is linked to punishment behavior. However, no clear evidence was provided regarding whether the effect of inter-brain connectivity on third-party punishment is mediated by local neuronal states. In this study, we further investigate whether resting-state neuronal activity in the alpha frequency range can predict individual differences in third-party punishment. More specifically, we show that the global resting-state connectivity between the right dorsolateral prefrontal and right temporo-parietal regions is negatively correlated with the level of third-party punishment. Additionally, individuals with stronger local resting-state long-range temporal correlations in the right temporo-parietal cortices demonstrated a lower level of third-party punishment. Thus, our results further support the idea that global and local neuronal dynamics can contribute to individual differences in third-party punishment.

Tandem alternative splice sites (TASS) is a special class of alternative splicing events that are characterized by a close tandem arrangement of splice sites. Most TASS lack functional characterization and are believed to arise from splicing noise. Based on the RNA-seq data from the Genotype Tissue Expression project, we present an extended catalogue of TASS in healthy human tissues and analyze their tissue-specific expression. The expression of TASS is usually dominated by one major splice site (maSS), while the expression of minor splice sites (miSS) is at least an order of magnitude lower. Among 46k miSS with sufficient read support, 9k (20%) are significantly expressed above the expected noise level, and among them 2.5k are expressed tissue-specifically. We found significant correlations between tissue-specific expression of RNA-binding proteins (RBP), tissue-specific expres- sion of miSS, and miSS response to RBP inactivation by shRNA. In combination with RBP profiling by eCLIP, this allowed prediction of novel cases of tissue-specific splicing regula- tion including a miSS in QKI mRNA that is likely regulated by PTBP1. The analysis of human primary cell transcriptomes suggested that both tissue-specific and cell-type-specific factors contribute to the regulation of miSS expression. More than 20% of tissue-specific miSS affect structured protein regions and may adjust protein-protein interactions or modify the stability of the protein core. The significantly expressed miSS evolve under the same selection pressure as maSS, while other miSS lack signatures of evolutionary selection and conservation. Using mixture models, we estimated that not more than 15% of maSS and not more than 54% of tissue-specific miSS are noisy, while the proportion of noisy splice sites among non-significantly expressed miSS is above 63%.

The ability of nucleic acids to form double-stranded structures is essential for all living systems on Earth. Current knowledge on functional RNA structures is focused on locally-occurring base pairs. However, crosslinking and proximity ligation experiments demonstrated that long-range RNA structures are highly abundant. Here, we present the most complete to-date catalog of conserved complementary regions (PCCRs) in human protein-coding genes. PCCRs tend to occur within introns, suppress intervening exons, and obstruct cryptic and inactive splice sites. Double-stranded structure of PCCRs is supported by decreased icSHAPE nucleotide accessibility, high abundance of RNA editing sites, and frequent occurrence of forked eCLIP peaks. Introns with PCCRs show a distinct splicing pattern in response to RNAPII slowdown suggesting that splicing is widely affected by co-transcriptional RNA folding. The enrichment of 3’-ends within PCCRs raises the intriguing hypothesis that coupling between RNA folding and splicing could mediate co-transcriptional suppression of premature pre-mRNA cleavage and polyadenylation.

Changes in the parameters of miniature endplate potential (MEPP) of mouse diaphragm caused by exogenous application of two classical endocannabinoids, 2-arachidonoylglycerol (2-AG) (1 μM) and anandamide (AEA) (30 μM), were compared. A slowly developing stable increase in the MEPP amplitude by 50%, without affecting the frequency of MEPPs, was caused by 2-AG. This effect was prevented by AM-251, an inverse agonist of CB1-receptors, as well as by vesamicol, a blocker of the vesicular acetylcholine (ACh) transporter. On the contrary, AEA did not cause significant changes in the MEPP amplitude but induced a slowly developing (within 2 h) increase in MEPP frequency by 75% on average. The effect of AEA was prevented by AM-251 (1 μM) as well as by blocking of L-type Ca2+-channels with nitrendipine (1 μM) and inhibition of PKA activity by H89 (1 μM). It was concluded that both 2-AG and AEA are able to exert a noncanonical facilitating presynaptic effect on spontaneous ACh release. Even though these endocannabinoids activate the same type of CB-receptors, their facilitating effects do not overlap and are strictly aimed either at potentiating the size of ACh quanta (in case of 2-AG) or increasing the frequency of MEPP (in case of AEA). We assume that different intracellular targets and signaling pathways may be involved in the differentiated facilitating effects of 2-AG and AEA in mouse neuromuscular junctions.

Effectiveness of various emotion regulation (ER) strategies have received much attention in recent research. Among the most studied ER strategies are cognitive reappraisal and expressive suppression. However, the evidence of their effectiveness is controversial and depends on the measures used. The aim of the present study was to compare the effectiveness of cognitive reappraisal and expressive suppression strategies of ER via different measures such as self-report, facial expressions (zygomaticus major and corrugator supercilii electromyography), and physiological assessment (skin conductance response and heart rate deceleration). Participants were presented with intensely unpleasant or neutral pictures and performed ER tasks. We expected that the implementation of ER strategies would reduce negative emotions, and cognitive reappraisal would produce greater reduction in negative emotions compared to expressive suppression. Self-report data showed that reappraisal had a greater effect on the reduction of negative emotions compared to suppression. There was no difference between reappraisal and suppression assessed with skin conductance response and electromyography. Curiously, heart rate deceleration increased while participants tried to suppress their emotional expressions, which could reflect efforts exerted in the attempt to suppress. The ER strategies reduced negative emotions during the presentation of unpleasant pictures partially in skin conductance response and heart rate deceleration. Overall, reappraisal is more effective in changing subjective experience, whereas the physiological reactions do not differ substantially between the two ER strategies explored. We therefore recommend that the assessment of ER strategies in the laboratory should accommodate more than one type of measures to come to more reliable conclusions.  

In humans, trophoblast hypoxia during placental development can be a cause of serious pregnancy complications, such as preeclampsia and fetal growth restriction. The pathogenesis of these conditions is not fully clear and may be associated with changed expression of some genes and regulatory molecules, including miRNA, in trophoblast cells. The aim of this study was to analyze miRNA profiles and measure the expression of their target genes in a model of trophoblast hypoxia. Human choriocarcinoma BeWo b30 cells were used as a trophoblast model. Hypoxia was induced by cobalt chloride (CoCl2) and an oxyquinoline derivative. MRNA and miRNA expression profiles were evaluated by means of next generation sequencing (NGS); the expression of individual genes was analyzed by PCR. We studied the secondary structure of mRNAs of target genes for those miRNAs whose expression had changed significantly and analyzed potential competition between these miRNAs for the binding site. The observed changes in the expression of the key genes involved in the response to hypoxia confirmed the feasibility of using CoCl2 and the oxyquinoline derivative as hypoxia inducers. The analysis revealed an increase in miR-374 levels following the activation of the hypoxia pathway in our trophoblast model. The changes were accompanied by a reduction in FOXM1 mRNA expression; this mRNA is a target for hsa-miR-374a-5p and hsa-miR374b-5p, which can compete with hsa-miR-21-5p for the binding sites on FOXM1 mRNA. The involvement of FOXM1 in the regulation of the invasive cell potential suggests the role of miR-374 and FOXM1 in the pathogenesis of disrupted trophoblast invasion during placental development as predisposing for fetal growth restriction and preeclampsia.

Breast cancer (BC) is the leading cause of death from malignant neoplasms among women worldwide, and metastatic BC presents the biggest problems for treatment. Previously, it was shown that lower expression of ELOVL5 and IGFBP6 genes is associated with a higher risk of the formation of distant metastases in BC. In this work, we studied the change in phenotypical traits, as well as in the transcriptomic and proteomic profiles of BC cells as a result of the stable knockdown of ELOVL5and IGFBP6 genes. The knockdown of ELOVL5 and IGFBP6 genes was found to lead to a strong increase in the expression of the matrix metalloproteinase (MMP) MMP1. These results were in good agreement with the correlation analysis of gene expression in tumor samples from patients and were additionally confirmed by zymography. The knockdown of ELOVL5 and IGFBP6 genes was also discovered to change the expression of a group of genes involved in the formation of intercellular contacts. In particular, the expression of the CDH11 gene was markedly reduced, which also complies with the correlation analysis. The spheroid formation assay showed that intercellular adhesion decreased as a result of the knockdown of the ELOVL5 and IGFBP6 genes. Thus, the obtained data indicate that malignant breast tumors with reduced expression of the ELOVL5 and IGFBP6 genes can metastasize with a higher probability due to a more efficient invasion of tumor cells.

As an effort to help contain the COVID-19 pandemic, large numbers of SARS-CoV-2 genomes have been sequenced from all continents. More than one million viral sequences are publicly available as of April 2021. Many studies estimate viral genealogies from these sequences, as these can provide valuable information about the spread of the pandemic across time and space. Additionally such data are a rich source of information about molecular evolutionary processes including natural selection, for example allowing the identification and investigating the spread of new variants conferring transmissibility and immunity evasion advantages to the virus. To validate new methods and to verify results resulting from these vast datasets, one needs an efficient simulator able to simulate the pandemic to approximate world-scale scenarios and generate viral genealogies of millions of samples. Here, we introduce a new fast simulator VGsim which addresses this problem. The simulation process is split into two phases. During the forward run the algorithm generates a chain of events reflecting the dynamics of the pandemic using an hierarchical version of the Gillespie algorithm. During the backward run a coalescent-like approach generates a tree genealogy of samples conditioning on the events chain generated during the forward run. Our software can model complex population structure, epistasis and immunity escape. The code is freely available at https://github.com/Genomics-HSE/VGsim.

Adaptive introgression - the flow of adaptive genetic variation between species or populations - has attracted significant interest in recent years and it has been implicated in a number of cases of adaptation, from pesticide resistance and immunity, to local adaptation. Despite this, methods for identification of adaptive introgression from population genomic data are lacking. Here, we present Ancestry_HMM-S, a Hidden Markov Model based method for identifying genes undergoing adaptive introgression and quantifying the strength of selection acting on them. Through extensive validation, we show that this method performs well on moderately sized datasets for realistic population and selection parameters. We apply Ancestry_HMM-S to a dataset of an admixed Drosophila melanogaster population from South Africa and we identify 18 loci which show signatures of adaptive introgression, four of which have previously been shown to confer resistance to insecticides. Ancestry_HMM-S provides a powerful method for inferring adaptive introgression in datasets that are typically collected when studying admixed populations. This method will enable powerful insights into the genetic consequences of admixture across diverse populations. Ancestry_HMM-S can be downloaded from https://github.com/jesvedberg/Ancestry_HMM-S/.

The ongoing pandemic of SARS-CoV-2 presents novel challenges and opportunities for the use of phylogenetics to understand and control its spread. Here, we analyze the emergence of SARS-CoV-2 in Russia in March and April 2020. Combining phylogeographic analysis with travel history data, we estimate that the sampled viral diversity has originated from 67 closely timed introductions into Russia, mostly in late February to early March. All but one of these introductions came from non-Chinese sources, suggesting that border closure with China has helped delay establishment of SARS-CoV-2 in Russia. These introductions resulted in at least 9 distinct Russian lineages corresponding to domestic transmission. A notable transmission cluster corresponded to a nosocomial outbreak at the Vreden hospital in Saint Petersburg; phylodynamic analysis of this cluster reveals multiple (2-4) introductions each giving rise to a large number of cases, with a high initial effective reproduction number of 3.7 (2.5-5.0).

The general goal of this paper is to gather and review several methods from homotopy and combinatorial topology and formal concepts analysis (FCA) and analyze their connections. FCA appears naturally in the problem of combinatorial simplification of simplicial complexes and allows to see a certain duality on a class of simplicial complexes. This duality generalizes Poincare duality on cell subdivisions of manifolds. On the other hand, with the notion of a topological formal context, we review the classical proofs of two basic theorems of homotopy topology: Alexandrov Nerve theorem and Quillen--McCord theorem, which are both important in the applications. A brief overview of the applications of the Nerve theorem in brain studies is given. The focus is made on the task of the external stimuli space reconstruction from the activity of place cells. We propose to use the combination of FCA and topology in the analysis of neural codes. The lattice of formal concepts of a neural code is homotopy equivalent to the nerve complex, but, moreover, it allows to analyse certain implication relations between collections of neural cells.

The most common tools to understand perception of food products are hall-tests, surveys, observations, etc. However to get reliable results these approaches require large samples, making them costly and time-consuming. Furthermore, they are also highly expert-dependent and rely on the assumption that study participants can express their preferences consciously and explicitly. Here we suggested an EEG-based approach to evaluate perceived product similarity in a cross-modal taste-visual task. Two candidate neurometrics measured from Fz electrode were tested: the amplitude of N430-620 from evoked response potentials (ERP) and the power of induced gamma oscillations during 400-600 ms period after visual stimulus presentation. Both suggested metrics showed a strong correlation with the perceived similarity scores at both individual and group levels, however N430-630 had greater inter-subject variability making it less suitable for practical applications. The results based on the power of induced gamma oscillations (N=18) not only reflected the results from traditional hall-tests (N=200) but also allowed better discrimination between different food products.

Admixture is increasingly being recognized as an important factor in evolutionary genetics. The distribution of genomic admixture tracts, and the resulting effects on admixture linkage disequilibrium, can be used to date the timing of admixture between species or populations. However, the theory used for such prediction assumes selective neutrality despite the fact that many famous examples of admixture involve natural selection acting for or against admixture. In this paper, we investigate the effects of positive selection on the distribution of tract lengths. We develop a theoretical framework that relies on approximating the trajectory of the selected allele using a logistic function. By numerically calculating the expected allele trajectory, we also show that the approach can be extended to cases where the logistic approximation is poor due to the effects of genetic drift. Using simulations, we show that the model is highly accurate under most scenarios. We use the model to show that positive selection on average will tend to increase the admixture tract length. However, perhaps counter-intuitively, conditional on the allele frequency at the time of sampling, positive selection will actually produce shorter expected tract lengths. We discuss the consequences of our results in interpreting the timing of the introgression of EPAS1 from Denisovans into the ancestors of Tibetans.

Estimation of the relationship between DNA sequences is one of the most important problems in genomics. Understanding these relationships is central to de- mographic inference, correction of population structure in GWAS, identifying signals of selection etc. The data structure containing the full information about sample genealogy is called the ancestral recombination graph (ARG). However, ARG inference is a very dicult problem, not least due to a very complex state space. In this work we describe a new approach for fast and scalable generation of local tree topologies relating large numbers of haplotypes. Our method is closely related to the estimation of ARG, and captures both local and global properties of an ARG. It is based on a data structure which we call tree consistent PBWT , a modi cation of PBWT data structure intro- duced by R. Durbin (2014). We also explore some methods to estimate the quality of the generated tree topologies and to make inferences based on them. At the end we discuss a probabilistic model which could potentially lead to the estimation of ARG node times.

Whether the motor cortex activation accompanying concrete verbs comprehension is necessary for verbs conceptual processing is still a hotly debated topic in the literature. Answering this question, we examined to what extent the more difficult access to verb semantics requires an additional engagement of cortical motor system in verb generation task. Using power suppression of MEG beta oscillations (15-30 Hz) as an index of sensorimotor activation, we presented to our participants the noun cues which either were strongly associated with a single verb and prompted the fast and effortless verb retrieval, or were weakly associated with multiple verbs and were more difficult to respond to. A whole-brain analysis of beta suppression revealed that the only cortical regions sensitive to the difficulty of semantic access were the higher order motor areas on the medial and lateral surfaces of the frontal lobe. This differential activation of cortical motor system accompanied effortful verb retrieval and preceded the preparation of vocal response for more than 500 milliseconds. Since the mid-frontal frontal brain areas are involved in maintaining abstract representations of actions during their initiating and planning, we argue that our finding supports the view that motor associations contribute to retrieval of verb semantics.

In most countries, women live longer than men. Differences in longevities are country-specific and change over time. We perform a cross-country panel data analysis in developed countries (OECD and EU) to study the gender-longevity gap dependence on various socio-economic indicators and test a number of contradicting theories. We show that a lower gender longevity gap is associated with a higher real GDP per capita, a higher level of urbanization, lower income inequality, lower per capita alcohol consumption and a better ecological environment. An increase in women’s aggregate unemployment rate and a decline in men’s unemployment are associated with a higher gap in life expectancies. The effect of the share of women in parliaments in the gender-longevity gap is estimated to have a U-shape; it has a better descriptive efficiency if taken with a 5-years lag, which approximately corresponds to the length of political cycles.

Human genetic variability is thought to account for a substantial fraction of individual biochemical characteristics — in biomedical sense, of individual drug response. However, only a handful of human genetic variants have been linked to medication outcomes. Here, we combine data on drug-protein interactions and human genome sequences to assess the impact of human variation on their binding affinity. Using data from the complexes of FDA-drugs and drug-like compounds, we predict SNPs substantially affecting the protein-ligand binding affinities. We estimate that an average individual carries ~6 SNPs affecting ~5 different FDA-approved drugs from among all of the approved compounds. SNPs affecting drug-protein binding affinity have low frequency in the population indicating that the genetic component for many ADEs may be highly personalized with each individual carrying a unique set of relevant SNPs. The reduction of ADEs, therefore, may primarily rely on the application of computational genome analysis in the clinic rather than the experimental study of common SNPs.

Despite the success of many countries in increasing energy saving and energy efficiency, the global energy consumption is expected to continue its growth. The main reasons are economic development and population growth happening primarily in developing and emerging economies, especially in India and China. In such circumstances fossil fuels will remain the dominant energy source in the medium and even long run. The present research paper aims at analyzing the current global trends in the energy sector identified through literature review and expert tools, and their influence on Russia. Considering a broad range of factors, the paper determined the following main challenges for the Russian energy sector: tightening competition at international energy markets, the need for comprehensive modernization and stronger energy efficiency measures, the need for technological catch-up in a number of energy sector segments, the need to increase recovery factor at traditional oilfields, and the need to diversify energy mix by increasing the share of renewables. The paper also considers the main rationale for the last challenge that include strengthened security, reliability and sustainability of the Russian energy sector. Among the key preconditions for advancements in renewable energy are improvements in investment climate, modernisation of the central grid and changes in energy policy. The paper is based on the outcomes of the first stage of the Foresight project devoted to renewable energy technologies.

The paper aims to reveal the relationship between improvement in human diet and transition to democracy. The spread of a ‘European diet’ – the diet with historically unprecedented high proportion of animal proteins in daily calories intake – is likely to be one of the factors of regime change since 1992. In contrast to other studies, I regard European diet as an outcome of long historical transformation and show that improvement in nutrition preceded regime change. To get data on nutrients consumption around the world I apply to the Food balance sheets data from FAOSTAT. Based on this data I are able to define a European diet as the one containing animal protein-rich items (mostly, meat and dairy), alcohol beverages and sugar. Using OLS, factor analysis and SEM I test the direct and indirect effects of the European diet on the chance of transition to democracy and find positive impact of improvement in diet on political change. My findings reveal that improvement in diet affects democratization, but not vice versa.

The Foresight study presented in this paper is devoted to the sustainable use of water resources in Russia. The authors analyse possible trajectories of development in the three thematic areas (i) sustainability of water systems; (ii) water use by households and in industry; and (iii) new water products and services. The Foresight methods cover expert interviews and seminars, desk research, and policy analysis. The state and corporate policy recommendations for the water sector offered in this study correspond with the water scenarios earlier identified by Saritas et al.: “Nearly ideal future”, “Losses and accidents”, “Problem conservation”, and “National Priority” [Saritas et al., 2015]. For each of these four scenarios, policy recommendations for water companies were identified covering new solutions (including technological innovations), new values and competencies, organisational changes, modernisation of the infrastructure, financial issues, and legal and regulatory changes. Moreover, we recommend certain policy measures and approaches to state policy in the water sector.  The paper concludes with the main directions and instruments for the sector’s development, which should be planned and implemented jointly by the government and businesses, as well as other stakeholders (organisations and people).

This article considers the uneven positions of school teachers in different regions of the Russian Federation. There exist numerous research works on the relation of school teachers’ salaries to the characteristics of regional educational systems and regional economies. A range of indicators is used to calculate school teachers’ salaries. It is necessary to consider the ratio of the teachers’ salary to the average salary in the region, the latter serving as a target indicator in government programs, in combination with other indicators, such as the ratio of the salary to the price of a fixed set of goods and services and the ratio of the teachers’ salary fund to total regional government expenditures. Research based on cluster data analysis statistical methods allowed the author to distinguish four types of regions. We used official data provided by Russian Federal State Statistics Service and the Russian Federal Treasury. The recommendations developed for each cluster of regions seek to improve the efficiency of the steps aimed at the implementation of the educational policy tasks through differentiating the support measures by the federal government

Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst ring. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance are in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst ring events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.

Humans often adjust their behavior to match the group norms. In this study, we used magnetoencephalographic (MEG) source imaging to investigate the electromagnetic responses to the perceived mismatch between individual and group opinions. After participants were exposed to group opinion that conflicted with their own, we observed an evoked response in the posterior medial prefrontal cortex (pMPFC) occurring around 200 ms, corresponding to the feedback-related negativity (FRN) – a component of the evoked response associated with processing negative feedback and reinforcement learning. This response was accompanied by an increase in  power of theta oscillations (4-8 Hz) over a number of frontal sites (including OFC and pMPFC). The magnitude of both evoked and induced responses to the perceived conflict with social norms was stronger in participants who showed relatively low conformity. Overall, our results suggest that the activation of the pMPFC following conflicts with group opinion, as recoded by MEG, may reflect an enhanced control state – a process complimentary to the reinforcement learning signal in the ventral striatum reported in previous studies of social conformity

Euroregions is an important and quite popular mechanism of cross-border cooperation. Character of institutions development differs essentially between three groups of states, which use this mechanism: old members of the European Union; new members of the European Union (entered the EU after 2003); CIS members. This comparative research is concerned with the main circumstances of euroregions development in three areas noted above. The analyses show the fundamental differences between three Euroregion cases: Oresund, Pskov-Livonia and Dnieper. Those differences are noticeable in legislative basic, financing, cooperation issues, and even in four basic Euroregions principles realizing. Meanwhile we see that after fifteen years of copying the Euroregions in post-soviet countries the positive shifts occur in CIS members’ government perception and in the decision making process.