Apologia of Modernity

Received 6 June 2017. Accepted 21 August 2017. Published online 29 September 2017.The article considers key factors and directions of the value-institutional evolution of Modernity as a political project. It is argued that the movement of humankind towards the globalised world paradoxically turned not into a denial, but rather into a consistent radicalisation of the axiological political foundations of Modernity. The thesis of the axiological unity and institutional diversity of global Modernity is advanced in opposition to the concept of pluralist modernity as a rhetorically veiled civilisational approach. It is asserted that the constant self-adjustment of the central value system of globalised Modernity is carried out in the context of a non-simultaneity effect, providing grounds for discussions about the insurmountability of pre-modern cultural barriers and traditions of different civilisations. The conclusion is justified that the success of the globalisation of Modernity is contingent upon the possibility of building out the already existing world economy to include world politics, since the economic assimilation of the world by capitalism has largely outstripped the counterbalancing possibilities of its global political regulatory and compensatory systems, contributing to the intensification of conflicts and various inequalities. The increasingly intensive interaction and interdependence of humanity at the global level first implies the creation of ethical mechanisms of world politics based on concern for the interests of humanity as a whole. In seeking the solution to this problem, it is increasingly necessary to go beyond archaised political forms and the logic of decision-making that relates to territorial nation-states. In the discussion about the ethical and political values and institutions of the global, second or late Modernity, the positionsof those subjects capable of presenting a moral game to humanity – open, egalitarian, universal, cosmopolitan approaches for solving general problems – will be a priori strengthened

Revolution and Modernity

Received 16 April 2018. Accepted 5 June 2018. Published online 1 July 2018.Revolution simultaneously legitimises and denies the coordinate centre of the political order of Modernity. It is difficult to describe the historical evolution from the early industrial, class-national forms of political organisation to late or global Modernity other than in terms of a low-intensity revolution in the rate of social change. On the other hand, this permanent modernisation is not revolutionary in the sense that the periodic splits of elites, colour revolutions, coups and national liberation movements do not in and of themselves make demands for fundamental change in the value-institutional core of the political order of Modernity. The potential for a new revolution can be consequent only on a repudiation of Modernity in favour of an alternative political project having a greater capability for universalisation and totalisation. If, in legitimising its liberal consensus and nation-state models as the dominant political format of their synthesis, capitalism is the value-institutional quintessence of the political order of Modernity, it is precisely in challenges to capitalism, the liberal consensus and nationalism that provide the most obvious means for crystallising revolutionary movements. From such a perspective, capitalism increasingly comes up against the global limits of its expansion, with class ideologies degenerating into a fragmented, technologically-intermediated populism, and nationstates experiencing increasing pressure from alternative political formats (city networks, multinational corporations, etc.) as they attempt to preserve the model of the social state. While various discourses and social groups profess to play the role of revolutionary utopias and subjects, in essence, their ability to present a totalising alternative to late Modernity remains an open question. A utopian systemic challenge to Modernity, connected with a morally more justified configuration and associated hierarchy of legitimate violence, is yet to emerge, whether from within Modernity or some source external to it. It is demonstrated that in the long term a serious (and possibly revolutionary) correction of the political order of modern societies will be capable of producing a rental transformation of capitalism and an expansion of the rent-class stratification mechanisms associated with precarisation, along with a reduction of social mobility trajectories and the prospects of active social groups.The article is prepared with the support of RFBR grant No. 18-011-00211 “Social Consensus in Russia: Mechanisms for Ideological and Institutional Regulation”

The Rise and Decline of Soviet Morality: Culture, Ideology, Collective Practices

Received 11 May 2020. Accepted 19 July 2020. Published online 9 October 2020.In the article, it is proposed that the collapse of Soviet society was presaged by a growing crisis in late Soviet morality. On the periphery of late Soviet morality, collective cultural practices are seen to have successfully functioned based on a limited ethics of virtue. In the absence of an alternative to Soviet ideology, social regulation started to draw upon values intended for the reproduction of local communities. A growing contradiction between the limited values of the new social class/corporate entities and the need to develop universal values for a big society is currently the key ideological legitimation problem facing the Russian political order.The work was supported by the research project “Social Cohesion in Russia and the Construction of Civil Identity as a Way to Achieve It” under the guidance of V. N. Rudenko (research program “Ethnic and Cultural Diversity of Russian Society and the Strengthening of Russian National Identity”)

Promoter targeted small RNAs induce long-term transcriptional gene silencing in human cells

Small RNAs targeted to gene promoters in human cells can mediate transcriptional gene silencing (TGS) by directing silent state epigenetic modifications to targeted loci. Many mechanistic details of this process remain poorly defined, and the ability to stably modulate gene expression in this manner has not been explored. Here we describe the mechanisms of establishment and maintenance of long-term transcriptional silencing of the human ubiquitin C gene (UbC). Sustained targeting of the UbC promoter with a small RNA for a minimum of 3 days resulted in long-term silencing which correlated with an early increase in histone methylation and a later increase in DNA methylation at the targeted locus. Transcriptional silencing of UbC required the presence of a promoter-associated RNA. The establishment and maintenance of the TGS were shown to require distinct protein factors. Argonaute 1 (Ago1), DNA methyltransferase 3a (DNMT3a) and histone deacetylase 1 (HDAC1) were required for the initiation of silencing, and DNA methyltransferase 1 (DNMT1) was necessary for maintenance. Taken together the data presented here highlight the cellular pathway with which noncoding RNAs interact to epigenetically regulate gene expression in human cells

Comparative Analysis of Human Protein-Coding and Noncoding RNAs between Brain and 10 Mixed Cell Lines by RNA-Seq

In their expression process, different genes can generate diverse functional products, including various protein-coding or noncoding RNAs. Here, we investigated the protein-coding capacities and the expression levels of their isoforms for human known genes, the conservation and disease association of long noncoding RNAs (ncRNAs) with two transcriptome sequencing datasets from human brain tissues and 10 mixed cell lines. Comparative analysis revealed that about two-thirds of the genes expressed between brain and cell lines are the same, but less than one-third of their isoforms are identical. Besides those genes specially expressed in brain and cell lines, about 66% of genes expressed in common encoded different isoforms. Moreover, most genes dominantly expressed one isoform and some genes only generated protein-coding (or noncoding) RNAs in one sample but not in another. We found 282 human genes could encode both protein-coding and noncoding RNAs through alternative splicing in the two samples. We also identified more than 1,000 long ncRNAs, and most of those long ncRNAs contain conserved elements across either 46 vertebrates or 33 placental mammals or 10 primates. Further analysis showed that some long ncRNAs differentially expressed in human breast cancer or lung cancer, several of those differentially expressed long ncRNAs were validated by RT-PCR. In addition, those validated differentially expressed long ncRNAs were found significantly correlated with certain breast cancer or lung cancer related genes, indicating the important biological relevance between long ncRNAs and human cancers. Our findings reveal that the differences of gene expression profile between samples mainly result from the expressed gene isoforms, and highlight the importance of studying genes at the isoform level for completely illustrating the intricate transcriptome

Negative Correlation between Expression Level and Evolutionary Rate of Long Intergenic Noncoding RNAs

Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The functions of the lncRNAs remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into the mode of evolution and the functional range of the lncRNA, they can be compared with much better characterized protein-coding genes. The evolutionary rate of the protein-coding genes shows a universal negative correlation with expression: highly expressed genes are on average more conserved during evolution than the genes with lower expression levels. This correlation was conceptualized in the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether long intergenic ncRNAs (lincRNAs) follow the same evolutionary trend and indeed detected a moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse lincRNA genes. The magnitude of the correlation for the lincRNAs is similar to that for equal-sized sets of protein-coding genes with similar levels of sequence conservation. Additionally, the expression level of the lincRNAs is significantly and positively correlated with the predicted extent of lincRNA molecule folding (base-pairing), however, the contributions of evolutionary rates and folding to the expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be a general feature of gene evolution that might be caused by similar deleterious effects of protein and RNA misfolding and/or other factors, for example, the number of interacting partners of the gene product

Mice Lacking Alkbh1 Display Sex-Ratio Distortion and Unilateral Eye Defects

Escherichia coli AlkB is a 2-oxoglutarate- and iron-dependent dioxygenase that reverses alkylated DNA damage by oxidative demethylation. Mouse AlkB homolog 1 (Alkbh1) is one of eight members of the newly discovered family of mammalian dioxygenases.In the present study we show non-Mendelian inheritance of the Alkbh1 targeted allele in mice. Both Alkbh1(-/-) and heterozygous Alkbh1(+/-) offspring are born at a greatly reduced frequency. Additionally, the sex-ratio is considerably skewed against female offspring, with one female born for every three to four males. Most mechanisms that cause segregation distortion, act in the male gametes and affect male fertility. The skewing of the sexes appears to be of paternal origin, and might be set in the pachythene stage of meiosis during spermatogenesis, in which Alkbh1 is upregulated more than 10-fold. In testes, apoptotic spermatids were revealed in 5-10% of the tubules in Alkbh1(-/-) adults. The deficiency of Alkbh1 also causes misexpression of Bmp2, 4 and 7 at E11.5 during embryonic development. This is consistent with the incompletely penetrant phenotypes observed, particularly recurrent unilateral eye defects and craniofacial malformations.Genetic and phenotypic assessment suggests that Alkbh1 mediates gene regulation in spermatogenesis, and that Alkbh1 is essential for normal sex-ratio distribution and embryonic development in mice

Histone Variants and Their Post-Translational Modifications in Primary Human Fat Cells

Epigenetic changes related to human disease cannot be fully addressed by studies of cells from cultures or from other mammals. We isolated human fat cells from subcutaneous abdominal fat tissue of female subjects and extracted histones from either purified nuclei or intact cells. Direct acid extraction of whole adipocytes was more efficient, yielding about 100 µg of protein with histone content of 60% –70% from 10 mL of fat cells. Differential proteolysis of the protein extracts by trypsin or ArgC-protease followed by nanoLC/MS/MS with alternating CID/ETD peptide sequencing identified 19 histone variants. Four variants were found at the protein level for the first time; particularly HIST2H4B was identified besides the only H4 isoform earlier known to be expressed in humans. Three of the found H2A potentially organize small nucleosomes in transcriptionally active chromatin, while two H2AFY variants inactivate X chromosome in female cells. HIST1H2BA and three of the identified H1 variants had earlier been described only as oocyte or testis specific histones. H2AFX and H2AFY revealed differential and variable N-terminal processing. Out of 78 histone modifications by acetylation/trimethylation, methylation, dimethylation, phosphorylation and ubiquitination, identified from six subjects, 68 were found for the first time. Only 23 of these modifications were detected in two or more subjects, while all the others were individual specific. The direct acid extraction of adipocytes allows for personal epigenetic analyses of human fat tissue, for profiling of histone modifications related to obesity, diabetes and metabolic syndrome, as well as for selection of individual medical treatments

Intronic L1 Retrotransposons and Nested Genes Cause Transcriptional Interference by Inducing Intron Retention, Exonization and Cryptic Polyadenylation

Transcriptional interference has been recently recognized as an unexpectedly complex and mostly negative regulation of genes. Despite a relatively few studies that emerged in recent years, it has been demonstrated that a readthrough transcription derived from one gene can influence the transcription of another overlapping or nested gene. However, the molecular effects resulting from this interaction are largely unknown.Using in silico chromosome walking, we searched for prematurely terminated transcripts bearing signatures of intron retention or exonization of intronic sequence at their 3' ends upstream to human L1 retrotransposons, protein-coding and noncoding nested genes. We demonstrate that transcriptional interference induced by intronic L1s (or other repeated DNAs) and nested genes could be characterized by intron retention, forced exonization and cryptic polyadenylation. These molecular effects were revealed from the analysis of endogenous transcripts derived from different cell lines and tissues and confirmed by the expression of three minigenes in cell culture. While intron retention and exonization were comparably observed in introns upstream to L1s, forced exonization was preferentially detected in nested genes. Transcriptional interference induced by L1 or nested genes was dependent on the presence or absence of cryptic splice sites, affected the inclusion or exclusion of the upstream exon and the use of cryptic polyadenylation signals.Our results suggest that transcriptional interference induced by intronic L1s and nested genes could influence the transcription of the large number of genes in normal as well as in tumor tissues. Therefore, this type of interference could have a major impact on the regulation of the host gene expression

Non-protein coding RNA biomarkers and differential expression in cancers: a review

<p>Abstract</p> <p>Background</p> <p>In these years a huge number of human transcripts has been found that do not code for proteins, named non-protein coding RNAs. In most cases, small (miRNAs, snoRNAs) and long RNAs (antisense RNA, dsRNA, and long RNA species) have many roles, functioning as regulators of other mRNAs, at transcriptional and post-transcriptional level, and controlling protein ubiquitination and degradation. Various species of npcRNAs have been found differentially expressed in different types of cancer. This review discusses the published data and new results on the expression of a subset of npcRNAs.</p> <p>Conclusion</p> <p>These results underscore the complexity of the RNA world and provide further evidence on the involvement of functional RNAs in cancer cell growth control.</p