Оценка неравномерности развития регионов РФ по социально-экономическим ресурсным составляющим

In the state strategy of the economic security of the Russian Federation the increased differentiation of regions and municipalities on the level and pace of socio-economic develop-ment is indicated as the main challenges, as well as the insufficient funding of industrial production, a weak innovation activity, lagging behind in the development and implementation of new and emerging technologies, increasing differentiation of the population by the income level, lack of labour resources, reduced quality and accessibility of education, health care and, as a result, the decline in the quality of the human capital.The purpose of this paper is to develop a system of integral indicators of resource components of socio-economic potential of the regions of the Russian Federation based on a legitimate, credible and accessible statistical data for the evaluation of their development unevenness. Materials and methods. Resource potential of the region is being considered as a collection of six groups of socio-economic indicators: fixed funds, financial and investment resource, labour resource, science and innovation resources, information resource and social resource. Each group includes indicators that are directly related to the possibilities of production of goods and services. In accordance with the methodological approaches of the resource capabilities evaluation of the region on the basis of integral indicators the principles of completeness, adequacy, accessibility, universality and formalization of the indicators are used. Evaluation of a group of indicators and all indicators of groups as a whole is made according to the values of integral indicators of reduction or exaggeration in comparison with the reference values of the resource components. Various indicators in the group have a different level of im-pact on the gross regional product that is taken into account in assessing their weight indicators. Time series values of the resource components in each group correlate with the time series values of the gross regional product, the coefficients values of pair correlation are used to recalculate them into weighting coefficients. Formulas for evaluating the individual indicators in the group are developed, integral indicators of the group of resource components and integral indicators of the resource potential of the region as a whole.Results. Given the significant differentiation of regions of Russia according to various objective factors, it is considered appropriate to compare regions within Federal Districts. For the Central Federal District, the Moscow region is taken as the benchmark for comparison, and relative levels of reduction in the resource components of other regions are calculated relative to the level of indicators of its resource potential. Analysis of the data shows that the highest level of resource reduction components of the Ivanovo region is observed in the resource group of science and innovation – 77.1 %, resources of the fixed funds, financial-investment and labour resources are equal the value of this indicator – from 42.3% to 45.4 %. The integrated indicator of relative resource reduction components in the Ivanovo area totaled 41.9 %.Conclusion. Using statistical data for the Ivanovo and Yaroslavl regions as examples, calculations of integral indicators are carried out, which demonstrate the possibility of assessing the regional development unevenness by their resource component of socio-economic development.В Государственной стратегии экономической безопасности Российской Федерации в качестве основных вызовов указывается усиление дифференциации регионов и муниципальных образований по уровню и темпам социально-экономического развития, а также недостаточное финансирование промышленного производства, слабая инновационная активность, отставание в области разработки и внедрения новых и перспективных технологий, усиление дифференциации населения по уровню доходов, недостаточность трудовых ресурсов, снижение качества и доступности образования, медицинской помощи и, как следствие, снижение качества человеческого потенциала. Цель. Целью данной работы является разработка системы интегральных показателей ресурсных составляющих социально-экономического потенциала регионов РФ на основе легитимных, достоверных и общедоступных статистических данных для оценки неравномерности их развития.Материалы и методы. Ресурсный потенциал региона рассматривается как совокупность шести групп социально-экономических показателей: ресурсы основных фондов, финансово-инвестиционный ресурс, трудовой ресурс, ресурсы науки и инноваций, информационный ресурс и социальный ресурс. В каждую группу включаются показатели, которые имеют прямое отношение к возможностям производства товаров и услуг. В соответствии с методическими подходами оценки ресурсных возможностей региона на основе интегральных показателей, использованы принципы комплектности, достаточности, доступности информации, универсальности используемых показателей и формализации. Оценка группы показателей и всех показателей групп в целом производится по значениям интегральных показателей снижения или преувеличения по сравнению с эталонными значениями ресурсных составляющих. Различные показатели в группе имеют различный уровень влияния на валовый региональный продукт, что учитывается в сравнительной оценке по показателям их весомости. Временные ряды значений ресурсных составляющих в группах каждый в отдельности коррелируют с временным рядом значений валового регионального продукта, значения коэффициентов парной корреляции используются для перерасчета их в коэффициенты весомости. Разработаны формулы для оценки отдельных показателей в группе, интегральные показатели группы ресурсных составляющих и интегральные показатели ресурсного потенциала региона в целом.Результаты. Учитывая существенную дифференциацию регионов России по различным объективным факторам принимается целесообразным сравнивать регионы в рамках федеральных округов, для Центрального федерального округа в качестве эталона сравнения принимается Московская область, относительно уровня показателей ее ресурсного потенциала рассчитываются относительные уровни снижения ресурсных составляющих других регионов. Анализ полученных данных показывает, что наибольший уровень снижения ресурсных составляющих Ивановской области наблюдается по группе ресурсов науки и инноваций – 77,1%, ресурсы основных фондов, финансово-инвестиционный и трудовой ресурсы имеют близкие значения по этому показателю – от 42,3% до 45,4%. Интегральный показатель относительного уровня снижения ресурсных составляющих по Ивановской области в целом составил 41,9%.Заключение. На примере статистических данных по Ивановской и Ярославской областям выполнены расчеты интегральных показателей, которые демонстрируют возможность оценки неравномерности развития регионов по их ресурсной составляющей социально-экономического развития

NeuriteQuant: An open source toolkit for high content screens of neuronal Morphogenesis

<p>Abstract</p> <p>Background</p> <p>To date, some of the most useful and physiologically relevant neuronal cell culture systems, such as high density co-cultures of astrocytes and primary hippocampal neurons, or differentiated stem cell-derived cultures, are characterized by high cell density and partially overlapping cellular structures. Efficient analytical strategies are required to enable rapid, reliable, quantitative analysis of neuronal morphology in these valuable model systems.</p> <p>Results</p> <p>Here we present the development and validation of a novel bioinformatics pipeline called NeuriteQuant. This tool enables fully automated morphological analysis of large-scale image data from neuronal cultures or brain sections that display a high degree of complexity and overlap of neuronal outgrowths. It also provides an efficient web-based tool to review and evaluate the analysis process. In addition to its built-in functionality, NeuriteQuant can be readily extended based on the rich toolset offered by ImageJ and its associated community of developers. As proof of concept we performed automated screens for modulators of neuronal development in cultures of primary neurons and neuronally differentiated P19 stem cells, which demonstrated specific dose-dependent effects on neuronal morphology.</p> <p>Conclusions</p> <p>NeuriteQuant is a freely available open-source tool for the automated analysis and effective review of large-scale high-content screens. It is especially well suited to quantify the effect of experimental manipulations on physiologically relevant neuronal cultures or brain sections that display a high degree of complexity and overlap among neurites or other cellular structures.</p

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

IMMUNOLOGICAL CHARACTERISTIC OF SYNTHETIC PEPTIDES SIMILAR TO ACTUAL HIV ANTIGEN DETERMINANTS

The development of HIV vaccine remains an important goal in prophylaxis and therapy of HIV/ AIDS epidemics. There are various approaches for development of а candidate vaccine based on induction of neutralizing antibodies and cell-mediated immunity. Synthetic peptides are considered promising vaccine antigens since they are capable of activating both humoral and cellular immune response. HIV-1 envelope gp120 is the target for neutralizing antiviral antibodies. The V3 region of the HIV-1 gp120 is highly immunogenic and important for the virus-coreceptor interaction. In a RV144 vaccine trial, the levels of vaccine-induced IgG antibodies recognizing V1V2 regions from multiple HIV-1 subtypes show inverse correlations with a risk for HIV-1 infection. Meanwhile, HIV is characterized by high diversity. The consensus and mosaic immunogens are complete but artificial proteins, which are computationally designed to elicit immune responses with improved cross-reactive broadness. We have been studied immunogenic properties of synthetic peptides derived from V1, V2, V3 loop regions of the consensus M HIV1 (CON-S) sequence group of the gp 120 envelope protein and V3 loop derived from a Russian RUA022a2 isolate. These peptides specifically reacted to HIV-positive sera in ELISA, thus indicating their similarity to appropriate HIV proteins. The peptides proved to be weakly immunogenic. Therefore, Freund complete adjuvant was used to enhance peptide immunogenicity. To assess the immunogenicity, the mice were immunized with a peptide mixture. Antibodies have been developed to every peptide from the mixture, being, predominantly, of IgG isotype. The antibody titers depended on the length of peptide sequences. However, the sera from immunized mice did not have a HIV neutralizing activity. The serum neutralization was assessed by pseudovirus-based assay, using a molecular clone of virus isolates CAP 45.2.00.G3 and QH.209.14.M.EnvA2. The virus neutralization is a complex process and may be influenced by several factors, such as antibody titer, isotype, or antibody structure. Probably, to induce neutralizing antibodies by this peptide mixture, it is necessary to choose appropriate adjutants and immunization schedule. Moreover, it was shown that peptides could increase in vitro virus infectivity in pseudovirus-based model, using the CAP 45.2.00.G3, QH209.14M.ENV.A2, QD435.100M.ENV.E1 molecular clone. These viral isolates belong to different HIV-1 subtypes

Formin1 Mediates the Induction of Dendritogenesis and Synaptogenesis by Neurogenin3 in Mouse Hippocampal Neurons

Neurogenin3, a proneural transcription factor controlled by Notch receptor, has been recently shown to regulate dendritogenesis and synaptogenesis in mouse hippocampal neurons. However, little is known about the molecular mechanisms involved in these actions of Ngn3. We have used a microarray analysis to identify Ngn3 regulated genes related with cytoskeleton dynamics. One of such genes is Fmn1, whose protein, Formin1, is associated with actin and microtubule cytoskeleton. Overexpression of the Fmn1 isoform-Ib in cultured mouse hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs at 4 days in vitro. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritogenesis and synaptogenesis and indicate that this protein is a key component of the Ngn3 signaling pathway that controls neuronal differentiation

The Caenorhabditis elegans Eph Receptor Activates NCK and N-WASP, and Inhibits Ena/VASP to Regulate Growth Cone Dynamics during Axon Guidance

The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity

SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism

Genetic mutations of SHANK3 have been reported in patients with intellectual disability, autism spectrum disorder (ASD) and schizophrenia. At the synapse, Shank3/ProSAP2 is a scaffolding protein that connects glutamate receptors to the actin cytoskeleton via a chain of intermediary elements. Although genetic studies have repeatedly confirmed the association of SHANK3 mutations with susceptibility to psychiatric disorders, very little is known about the neuronal consequences of these mutations. Here, we report the functional effects of two de novo mutations (STOP and Q321R) and two inherited variations (R12C and R300C) identified in patients with ASD. We show that Shank3 is located at the tip of actin filaments and enhances its polymerization. Shank3 also participates in growth cone motility in developing neurons. The truncating mutation (STOP) strongly affects the development and morphology of dendritic spines, reduces synaptic transmission in mature neurons and also inhibits the effect of Shank3 on growth cone motility. The de novo mutation in the ankyrin domain (Q321R) modifies the roles of Shank3 in spine induction and morphology, and actin accumulation in spines and affects growth cone motility. Finally, the two inherited mutations (R12C and R300C) have intermediate effects on spine density and synaptic transmission. Therefore, although inherited by healthy parents, the functional effects of these mutations strongly suggest that they could represent risk factors for ASD. Altogether, these data provide new insights into the synaptic alterations caused by SHANK3 mutations in humans and provide a robust cellular readout for the development of knowledge-based therapies

Eps8 Regulates Axonal Filopodia in Hippocampal Neurons in Response to Brain-Derived Neurotrophic Factor (BDNF)

A novel signaling cascade controlling actin polymerization in response to extracellular signals regulates filopodia formation and likely also neuronal synapse formation

Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset?

White matter bundle segmentation using diffusion MRI fiber tractography has become the method of choice to identify white matter fiber pathways in vivo in human brains. However, like other analyses of complex data, there is considerable variability in segmentation protocols and techniques. This can result in different reconstructions of the same intended white matter pathways, which directly affects tractography results, quantification, and interpretation. In this study, we aim to evaluate and quantify the variability that arises from different protocols for bundle segmentation. Through an open call to users of fiber tractography, including anatomists, clinicians, and algorithm developers, 42 independent teams were given processed sets of human whole-brain streamlines and asked to segment 14 white matter fascicles on six subjects. In total, we received 57 different bundle segmentation protocols, which enabled detailed volume-based and streamline-based analyses of agreement and disagreement among protocols for each fiber pathway. Results show that even when given the exact same sets of underlying streamlines, the variability across protocols for bundle segmentation is greater than all other sources of variability in the virtual dissection process, including variability within protocols and variability across subjects. In order to foster the use of tractography bundle dissection in routine clinical settings, and as a fundamental analytical tool, future endeavors must aim to resolve and reduce this heterogeneity. Although external validation is needed to verify the anatomical accuracy of bundle dissections, reducing heterogeneity is a step towards reproducible research and may be achieved through the use of standard nomenclature and definitions of white matter bundles and well-chosen constraints and decisions in the dissection process

The Rac GTP Exchange Factor TIAM-1 Acts with CDC-42 and the Guidance Receptor UNC-40/DCC in Neuronal Protrusion and Axon Guidance

The mechanisms linking guidance receptors to cytoskeletal dynamics in the growth cone during axon extension remain mysterious. The Rho-family GTPases Rac and CDC-42 are key regulators of growth cone lamellipodia and filopodia formation, yet little is understood about how these molecules interact in growth cone outgrowth or how the activities of these molecules are regulated in distinct contexts. UNC-73/Trio is a well-characterized Rac GTP exchange factor in Caenorhabditis elegans axon pathfinding, yet UNC-73 does not control CED-10/Rac downstream of UNC-6/Netrin in attractive axon guidance. Here we show that C. elegans TIAM-1 is a Rac-specific GEF that links CDC-42 and Rac signaling in lamellipodia and filopodia formation downstream of UNC-40/DCC. We also show that TIAM-1 acts with UNC-40/DCC in axon guidance. Our results indicate that a CDC-42/TIAM-1/Rac GTPase signaling pathway drives lamellipodia and filopodia formation downstream of the UNC-40/DCC guidance receptor, a novel set of interactions between these molecules. Furthermore, we show that TIAM-1 acts with UNC-40/DCC in axon guidance, suggesting that TIAM-1 might regulate growth cone protrusion via Rac GTPases in response to UNC-40/DCC. Our results also suggest that Rac GTPase activity is controlled by different GEFs in distinct axon guidance contexts, explaining how Rac GTPases can specifically control multiple cellular functions