The analysis of the International Practice of Realization and Financing of Projects of Public-Private Partnership in Development of Regional Infrastructure

In the article, the analysis of the international practice of realization and resource providing projects of the public-private partnership is carried out. Distributions of the public-private partnership projects on branches in the countries with the different level of economic development is described. Organizational and economic mechanisms of realization of public-private partnership in such countries as Great Britain, Australia, Ireland, Brazil and China is revealed

Emerging drugs for the treatment of vitiligo

Introduction: Vitiligo is a relatively common autoimmune depigmenting disorder of the skin. There has been a great advance in understanding the pathological basis, which has led to the development and utilization of various new molecules in treating vitiligo. This review aims at a comprehensively describing the treatments available and the emerging treatment aspects and the scope for future developments. Areas covered: This study comprehensively summarizes the current concepts in the pathogenesis of vitiligo with special focus on the cytokine and signaling pathways, which are the targets for newer drugs. JAK kinase signaling pathways and the cytokines involved are the focus of vitiligo treatment in current research, followed by antioxidant mechanisms and repigmenting mechanisms. Topical immunosuppressants may be an alternative to steroids in localized vitiligo. Newer repigmenting agents like basic fibroblast growth factors, afamelanotide have been included and a special emphasis is laid on the upcoming targeted immunotherapy. Expert opinion: The treatment of vitiligo needs to be multimodal with emphasis on targeting different limbs of the pathogenesis. Topical and oral JAK inhibitors are the most promising new class of drugs currently available for treating vitiligo and acts best in conjunction with NB-UVB

ТЕОРИЯ ФИНАНСОВЫХ ИННОВАЦИЙ. КРИТИЧЕСКИЙ ОБЗОР ОСНОВНЫХ ПОДХОДОВ

In times of crises, attempts are often made to blame all the troubles on financial innovations and reconsider their role in the progress. At the same time scientific publications also discuss positive aspects of financial innovations. The paper makes a critical analysis of the impact of financial innovation options on the financial system balance with account for expectations and behavior of market players. The research compares different views on the role and place of innovations in finance, their contribution to the stabilization or undermining of the economy. At the World Economic Forum, it was agreed that none of numerous definitions are able to fully cover the complexity of innovations in the sphere of financial services where a new product can combine a variety of functions, including circulation, organization form, marketing, customer context, and develop the supporting infrastructure. However, the definition was necessary. On its basis a number of clarifications and constructions were made: the transition to various theoretical schemes was performed; the adaptability of markets and countries to the risks associated with financial innovations was assessed; preparations for restructuring of the organizational structures, management mechanisms, technological processes were made to minimize undesirable effects and improve the positive impact of innovations.Как правило, в ходе кризисов наблюдаются попытки обвинить во всех бедах финансовые инновации и в связи с этим пересмотреть их роль в прогрессе. В то же время в различных научных исследованиях рассматриваются положительные стороны финансовых инноваций. В статье предлагается критический разбор вариантов воздействия финансовых инноваций на равновесие финансовой системы с учетом ожидания и поведения рыночных игроков. Исследование проводилось преимущественно на базе сравнений различных подходов по вопросам роли и места инноваций в финансах, участию их в стабилизации и расшатывании хозяйства. На Мировом экономическом форуме было признано, что ни одно из многочисленных определений не в состоянии полностью охватить всю сложность инноваций в сфере финансовых услуг, где один новый продукт может объединять разнообразные функции: обращение, организационную форму, маркетинг, клиентский контекст, а также развивать вспомогательную инфраструктуру. Однако определение необходимо. С его помощью проведен целый ряд уточнений и построений: совершен переход к различным теоретическим конструкциям; дана оценка уровням адаптивности рынков и государств к рискам, связанным с финансовыми новшествами; подготовлена перестройка организационных структур, механизмов управления, технологических процессов в направлении оптимизации нежелательных последствий и усиления позитивных воздействий инноваций

Transcription factor trapping by RNA in gene regulatory elements

Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs.National Institutes of Health (U.S.) (HG002668)Biogen, Inc

Genome-wide determination of drug localization

A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide new and important insights into chemical perturbation of cellular function. Here we describe a method that couples ligand-affinity capture and massively parallel DNA sequencing (Chem-seq) to identify the sites bound by small chemical molecules throughout the human genome. We show how Chem-seq can be combined with ChIP-seq to gain unique insights into the interaction of drugs with their target proteins throughout the genome of tumor cells. These methods provide a powerful approach to enhance understanding of therapeutic action and characterize the specificity of chemical entities that interact with DNA or genome-associated proteins

Genome of Linum usitatissimum convar. crepitans expands the view on the section Linum

Sequencing whole plant genomes provides a solid foundation for applied and basic studies. Genome sequences of agricultural plants attract special attention, as they reveal information on the regulation of beneficial plant traits. Flax is a valuable crop cultivated for oil and fiber. Genome sequences of its representatives are rich sources of genetic information for the improvement of cultivated forms of the plant. In our work, we sequenced the first genome of flax with the dehiscence of capsules—Linum usitatissimum convar. сrepitans (Boenn.) Dumort—on the Oxford Nanopore Technologies (ONT) and Illumina platforms. We obtained 23 Gb of raw ONT data and 89 M of 150 + 150 paired-end Illumina reads and tested different tools for genome assembly and polishing. The genome assembly produced according to the Canu—Racon ×2—medaka—POLCA scheme had optimal contiguity and completeness: assembly length—412.6 Mb, N50—5.2 Mb, L50—28, and complete BUSCO—94.6% (64.0% duplicated, eudicots_odb10). The obtained high-quality genome assembly of L. usitatissimum convar. crepitans provides opportunities for further studies of evolution, domestication, and genome regulation in the section Linum

Multiple knockout mouse models reveal lincRNAs are required for life and brain development

Many studies are uncovering functional roles for long noncoding RNAs (lncRNAs), yet few have been tested for in vivo relevance through genetic ablation in animal models. To investigate the functional relevance of lncRNAs in various physiological conditions, we have developed a collection of 18 lncRNA knockout strains in which the locus is maintained transcriptionally active. Initial characterization revealed peri- and postnatal lethal phenotypes in three mutant strains (Fendrr, Peril, and Mdgt), the latter two exhibiting incomplete penetrance and growth defects in survivors. We also report growth defects for two additional mutant strains (linc–Brn1b and linc–Pint). Further analysis revealed defects in lung, gastrointestinal tract, and heart in Fendrr−/− neonates, whereas linc–Brn1b−/− mutants displayed distinct abnormalities in the generation of upper layer II–IV neurons in the neocortex. This study demonstrates that lncRNAs play critical roles in vivo and provides a framework and impetus for future larger-scale functional investigation into the roles of lncRNA molecules. DOI: http://dx.doi.org/10.7554/eLife.01749.00

Functional specialization of Piwi proteins in Paramecium tetraurelia from post-transcriptional gene silencing to genome remodelling

Proteins of the Argonaute family are small RNA carriers that guide regulatory complexes to their targets. The family comprises two major subclades. Members of the Ago subclade, which are present in most eukaryotic phyla, bind different classes of small RNAs and regulate gene expression at both transcriptional and post-transcriptional levels. Piwi subclade members appear to have been lost in plants and fungi and were mostly studied in metazoa, where they bind piRNAs and have essential roles in sexual reproduction. Their presence in ciliates, unicellular organisms harbouring both germline micronuclei and somatic macronuclei, offers an interesting perspective on the evolution of their functions. Here, we report phylogenetic and functional analyses of the 15 Piwi genes from Paramecium tetraurelia. We show that four constitutively expressed proteins are involved in siRNA pathways that mediate gene silencing throughout the life cycle. Two other proteins, specifically expressed during meiosis, are required for accumulation of scnRNAs during sexual reproduction and for programmed genome rearrangements during development of the somatic macronucleus. Our results indicate that Paramecium Piwi proteins have evolved to perform both vegetative and sexual functions through mechanisms ranging from post-transcriptional mRNA cleavage to epigenetic regulation of genome rearrangements

Gene activation by metazoan enhancers: diverse mechanisms stimulate distinct steps of transcription

Enhancers can stimulate transcription by a number of different mechanisms which control different stages of the transcription cycle of their target genes, from recruitment of the transcription machinery to elongation by RNA polymerase. These mechanisms may not be mutually exclusive, as a single enhancer may act through different pathways by binding multiple transcription factors. Multiple enhancers may also work together to regulate transcription of a shared target gene. Most of the evidence supporting different enhancer mechanisms comes from the study of single genes, but new high-throughput experimental frameworks offer the opportunity to integrate and generalize disparate mechanisms identified at single genes. This effort is especially important if we are to fully understand how sequence variation within enhancers contributes to human disease