Strategic instruments to choose foreign target markets

Purpose: The paper aims to elaborate the principles and the authors’ original method to choose target markets of textile and fibers manufacturers when internationalizing their economic activity. The decision on foreign target markets must be very reasonable as having chosen a new foreign market the company put a lot of resources into it. Design/Methodology/Approach: The authors suggest to take into account three factors for the most perspective foreign markets for export interventions. The cash flow in foreign trade by specific materials (textiles and fibers) was estimated by each country – to select the countries depending on textiles and fibers import. Among those countries the markets' attractiveness was estimated by their size and growth intensity. After that general opportunities of doing business by Russian companies in the country were estimated using a complex index calculated on a basis of data characterizing import from Russia volume and its dynamics, transport accessibility, GDP Volume and Dynamics. Findings: The paper contains a set of data characterizing the most perspective countries for Russian textile companies export expansion – Cambodia, Bangladesh, Sri Lanka, Iran, Saudi Arabia, Morocco, Nicaragua, Viet Nam. Central and Eastern European countries (Romania, Poland, Slovenia), United Kingdom, USA, Canada are attractive from a point of view of potential prospects of business development in the country, however cooperation with them may be difficult due to some serious barriers on entering the markets. Practical Implications: The matrix can be used in managerial practices of different companies oriented on their international business activities expanding. The results of the new methods implementation (the list of the most perspective foreign markets) can be used by for management of the Russian textile companies oriented on foregn markets. Originality/Value: The paper contains a new method of foreign target markets choosing and a new strategic instrument – the matrix of export expansion markets choosing.peer-reviewe

The priority choice in the process of strategy working-out of the social economic micro region development

The development of the social economic strategies progress of the micro region namely the choice of priority industries which progress is to be supported by the authorities. The given article provides detailed description of a special authors’ approach how to analyze of perceptivity investment level into different sectors in frames of strategies working-out of the social economic development of the micro region. This approach is based on the creation of a special scale within its formation special attention is paid to the identification of the life cycle stage of the industry under analyses besides the potential development possibility of industries available for resources usage.peer-reviewe

A Small Conductance Calcium-Activated K⁺ Channel in C. elegans, KCNL-2, Plays a Role in the Regulation of the Rate of Egg-Laying

In the nervous system of mice, small conductance calcium-activated potassium (SK) channels function to regulate neuronal excitability through the generation of a component of the medium afterhyperpolarization that follows action potentials. In humans, irregular action potential firing frequency underlies diseases such as ataxia, epilepsy, schizophrenia and Parkinson's disease. Due to the complexity of studying protein function in the mammalian nervous system, we sought to characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically tractable system in which the lineage of individual neurons was mapped from their early developmental stages. Sequence analysis of the KCNL-2 protein reveals that the six transmembrane domains, the potassium-selective pore and the calmodulin binding domain are highly conserved with the mammalian homologues. We used widefield and confocal fluorescent imaging to show that a fusion construct of KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C. elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2-dependent manner. Conversely, we show that transgenic lines that overexpress KCNL-2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the vulva of transgenic hermaphrodites is highly innervated by neuronal processes and by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2 functions in the nervous system of C. elegans to regulate the rate of egg-laying. © 2013 Chotoo et al

ОПТИМИЗАЦИЯ ТЕХНИКИ ЛАПАРОСКОПИЧЕСКОЙ НЕРВОСБЕРЕГАЮЩЕЙ РАДИКАЛЬНОЙ ПРОСТАТЭКТОМИИ

Objective: to determine the optimal technique of laparoscopic nerve-sparing radical prostatectomy (RPE). Materials and methods. The PubMed database was used to examine matters on the anatomy of the prostate, its surrounding structures, and different techniques of laporoscopic RPE (LRPE). This has led to the conclusion that the Brussels technique provides better results in nervesparing at LRPE. In July 2008 to July 2009, 17 laparoscopic radical prostatectomies (15 patients underwent extrafascial prostatectomy, 2 patients had interfascial prostatectomy) were performed using the Brussels technique via transperitoneal approach; the results were prospectively evaluated. Results. The mean follow-up was 5.3 months so we cannot adequately assess the results now. The health status of the patients was evaluated using the questionnaires (International Continence Society and International Index of Erectile Function-5) filled in by them before and after surgery. Four of 5 patients who had been followed up for more than 6 months were continent, 1 patient used 1 pad. Out of 2 patients with a median follow-up of 2 months who had led a sexual life before surgery (International Index of Erectile Function-5 greater than 20 scores), erection was preserved in one patient after bilateral nerve-sparing prostatectomy and not preserved in the other after unilateral one. Conclusion. Anterior approach to the prostate provides better control of the neurovascular bundles in the seminal vesicular region. The modified Brussels technique is more preferable in performing LRPE.Objective: to determine the optimal technique of laparoscopic nerve-sparing radical prostatectomy (RPE). Materials and methods. The PubMed database was used to examine matters on the anatomy of the prostate, its surrounding structures, and different techniques of laporoscopic RPE (LRPE). This has led to the conclusion that the Brussels technique provides better results in nervesparing at LRPE. In July 2008 to July 2009, 17 laparoscopic radical prostatectomies (15 patients underwent extrafascial prostatectomy, 2 patients had interfascial prostatectomy) were performed using the Brussels technique via transperitoneal approach; the results were prospectively evaluated. Results. The mean follow-up was 5.3 months so we cannot adequately assess the results now. The health status of the patients was evaluated using the questionnaires (International Continence Society and International Index of Erectile Function-5) filled in by them before and after surgery. Four of 5 patients who had been followed up for more than 6 months were continent, 1 patient used 1 pad. Out of 2 patients with a median follow-up of 2 months who had led a sexual life before surgery (International Index of Erectile Function-5 greater than 20 scores), erection was preserved in one patient after bilateral nerve-sparing prostatectomy and not preserved in the other after unilateral one. Conclusion. Anterior approach to the prostate provides better control of the neurovascular bundles in the seminal vesicular region. The modified Brussels technique is more preferable in performing LRPE

A transcriptomics-based drug repositioning approach to identify drugs with similar activities for the treatment of muscle pathologies in spinal muscular atrophy (SMA) models

© 2023 The Author(s). Published by Oxford University Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder caused by the reduction of survival of motor neuron (SMN) protein levels. Although three SMN-augmentation therapies are clinically approved that significantly slow down disease progression, they are unfortunately not cures. Thus, complementary SMN-independent therapies that can target key SMA pathologies and that can support the clinically approved SMN-dependent drugs are the forefront of therapeutic development. We have previously demonstrated that prednisolone, a synthetic glucocorticoid (GC) improved muscle health and survival in severe Smn-/-;SMN2 and intermediate Smn2B/- SMA mice. However, long-term administration of prednisolone can promote myopathy. We thus wanted to identify genes and pathways targeted by prednisolone in skeletal muscle to discover clinically approved drugs that are predicted to emulate prednisolone's activities. Using an RNA-sequencing, bioinformatics, and drug repositioning pipeline on skeletal muscle from symptomatic prednisolone-treated and untreated Smn-/-; SMN2 SMA and Smn+/-; SMN2 healthy mice, we identified molecular targets linked to prednisolone's ameliorative effects and a list of 580 drug candidates with similar predicted activities. Two of these candidates, metformin and oxandrolone, were further investigated in SMA cellular and animal models, which highlighted that these compounds do not have the same ameliorative effects on SMA phenotypes as prednisolone; however, a number of other important drug targets remain. Overall, our work further supports the usefulness of prednisolone's potential as a second-generation therapy for SMA, identifies a list of potential SMA drug treatments and highlights improvements for future transcriptomic-based drug repositioning studies in SMA.Peer reviewe

ТЕХНИЧЕСКИЕ ОСОБЕННОСТИ ВЫПОЛНЕНИЯ РАДИКАЛЬНОЙ ПРОСТАТЭКТОМИИ ДЛЯ РАННЕГО ВОССТАНОВЛЕНИЯ КОНТИНЕНЦИИ

The paper presents the technical characteristics of radical prostatectomy (RPE) for early continence recovery in patients with prostate cancer. Restoration of the fascial structures of the small pelvis after RPE has been found to promote early urinary continence recovery. A method for total restoration of the fascial structures of the small pelvis (an operation after A. Tewari) and a procedure for performing posterior suspension of urethrocystic neoanastomosis in Denonvilliers’ fascia length deficit are considered, which show the similar results in the time of continence recovery.Представлены технические особенности выполнения радикальной простатэктомии РПЭ для раннего восстановления континенции у больных раком предстательной железы. Установлено, что раннему восстановлению континенции способствует восстановление фасциальных структур малого таза после РПЭ. Рассмотрены метод тотального восстановления фасциальных структур малого таза (операция А. Tewari) и способ осуществления задней суспензии уретроцистонеоанастомоза при дефиците длины фасции Денонвилье, характеризующиеся аналогичными результатами относительно сроков восстановления континенции

Дифференциальная экспрессия микроРНК и их генов-мишеней при цервикальных интраэпителиальных неоплазиях разной степени тяжести

Background. Currently, little is known about the specific microRNAs involved in the development of cervical intraepithelial neoplasia (CIN1, 2, 3) and the transition to cancer in situ (CIS). Our meta-analysis allowed us to isolate 8 microRNAs (hsa-miR-1246, hsa-miR- 145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p) with potential significance in the progression of precancerous diseases to cervical cancer. Objective: to analyze the expression features of hsa-miR-1246, hsa-miR-145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p and their target genes, as well as genes associated with them in common signaling pathways in the tissues of the cervix in patients with CIN1–3 and CIS. Materials and methods. To assess the expression level of microRNA and matrixRNA, the quantitative polymerase chain reaction in real time method was used. Data analysis was carried out in the Python programming language using the SciPy library. Search for target genes was performed using the TarPmiR algorithm and the overrepresentation of microRNAs in signaling pathways (Over-Representation Analysis) was analyzed. To identify genes associated with target genes in common signaling pathways, GIANT (Genome-scale Integrated Analysis of gene Networks in Tissues) and network integration with several associations algorithms were used. Results. For microRNAs miR-145, miR-196b, miR-34a, miR-20a, miR-21, miR-375 and miR-96 a decrease in expression was found in the subgroup of patients with CIS, while for 4 microRNAs (miR-145, miR-34a, miR-20a and miR-375), an increase in the expression level was found for CIN1, 2. The detected features of microRNA expression in subgroups of patients with CIN1–3 and CIS also affected the expression of their target genes (CDKN2A, MKI67, TOP2A and CD82), as well as the genes associated with them in common signaling pathways (PGK1, THBS4 (TSP4) and ECM1). Conclusion. Thus, the study revealed that each degree of CIN is characterized by its own specific molecular profile – the differential expression of microRNAs, their target genes and the genes associated with them in the general signaling pathways.Введение. В настоящее время недостаточно известно о специфических микроРНК (мкРНК), задействованных в развитии цервикальной интраэпителиальной неоплазии I, II, III степеней тяжести (CIN1, 2, 3) и переходе к карциноме in situ (CIS). Проведенный нами ранее метаанализ позволил выделить 8 мкРНК (hsa-miR-1246, hsa-miR-145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p), обладающих потенциальной значимостью в прогрессировании предраковых заболеваний в рак шейки матки. Цель исследования – анализ особенностей экспрессии hsa-miR-1246, hsa-miR-145-5p, hsa-miR-196b-5p, hsa-miR-34a-5p, hsa-miR- 20a-5p, hsa-miR-21-5p, hsa-miR-375-5p, hsa-miR-96-5p и их генов-мишеней, а также генов, ассоциированных с ними в общих сигнальных путях, в тканях шейки матки у пациенток с CIN1–3 и CIS. Материалы и методы. Для оценки уровня экспрессии мкРНК и матричной РНК использовали метод количественной полимеразной цепной реакции в режиме реального времени. Анализ данных проводили на языке программирования Python с использованием библиотеки SciPy. Поиск генов-мишеней осуществляли с помощью алгоритма TarPmiR и анализировали избыточную представленность мкРНК в сигнальных путях (Over-Representation Analysis). Для выявления генов, ассоциированных с генами-мишенями в общих сигнальных путях, использовали алгоритмы GIANT (Genome-scale Integrated Analysis of gene Networks in Tissues) и «сетевая интеграция с несколькими ассоциациями». Результаты. Для мкРНК miR-145, miR-196b, miR-34a, miR-20a, miR-21, miR-375 и miR-96 обнаружено снижение экспрессии в подгруппе пациенток с CIS, при этом для 4 мкРНК (miR-145, miR-34a, miR-20a и miR-375) выявлено увеличение уровня экспрессии при CIN1, 2. Обнаруженные особенности экспрессии мкРНК в подгруппах пациенток с CIN1–3 и CIS были ассоциированы с экспрессией их генов-мишеней (CDKN2A, MKI67, TOP2A и CD82), а также генов, связанных с ними в общих сигнальных путях (PGK1, THBS4 (TSP4) и ECM1). Заключение. Результаты исследования позволили установить, что каждая степень CIN характеризуется особым молекулярным профилем – дифференциальной экспрессией мкРНК, их генов-мишеней и генов, ассоциированных с ними в общих сигнальных путях

Mouse Retinal Development: a Dark Horse Model for Systems Biology Research

The developing retina is an excellent model to study cellular fate determination and differentiation in the context of a complex tissue. Over the last decade, many basic principles and key genes that underlie these processes have been experimentally identified. In this review, we construct network models to summarize known gene interactions that underlie determination and fundamentally affect differentiation of each retinal cell type. These networks can act as a scaffold to assemble subsequent discoveries. In addition, these summary networks provide a rational segue to systems biology approaches necessary to understand the many events leading to appropriate cellular determination and differentiation in the developing retina and other complex tissues

Genetic modifiers ameliorate endocytic and neuromuscular defects in a model of spinal muscular atrophy

© 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.Background: Understanding the genetic modifiers of neurodegenerative diseases can provide insight into the mechanisms underlying these disorders. Here, we examine the relationship between the motor neuron disease spinal muscular atrophy (SMA), which is caused by reduced levels of the survival of motor neuron (SMN) protein, and the actin-bundling protein Plastin 3 (PLS3). Increased PLS3 levels suppress symptoms in a subset of SMA patients and ameliorate defects in SMA disease models, but the functional connection between PLS3 and SMN is poorly understood.Results: We provide immunohistochemical and biochemical evidence for large protein complexes localized in vertebrate motor neuron processes that contain PLS3, SMN and members of the hnRNP F/H family of proteins. Using a Caenorhabditis elegans (C. elegans) SMA model, we determine that overexpression of PLS3 or loss of the C. elegans hnRNP F/H ortholog SYM-2 enhances endocytic function and ameliorates neuromuscular defects caused by decreased SMN-1 levels. Furthermore, either increasing PLS3 or decreasing SYM-2 levels suppresses defects in a C. elegans ALS model.Conclusions: We propose that hnRNP F/H act in the same protein complex as PLS3 and SMN and that the function of this complex is critical for endocytic pathways, suggesting that hnRNP F/H proteins could be potential targets for therapy development.Peer reviewe

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo