Search results for: regional expression

Authors: Samina Jam Nazeer Ahmad, Samia Yasin, Ijaz Ahmad, Muhammad Tahir, Jam Nazeer Ahmad

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Phytoplasmas are phloem-inhibited plant pathogenic bacteria that are transferred by insect vectors. Among biotic factors, Phytoplasma infection induces abnormality influencing the physiology as well as morphology of plants. In 16Sr-IX group phytoplasma-infected brassica compestris, flower abnormalities have been associated with changes in the expression of floral development genes. To determine whether methylation was involved in down-regulation of flower development, the process of DNA methylation and Demethylation was investigated as a possible mechanism for regulation of floral gene expression in phytoplasma infected Brassica transmitted by Orosious orientalis vector by using RT-PCR, MSRE-PCR, Southern blotting, Bisulfite Sequencing, etc. Transcriptional expression of methylated genes was found to be globally down-regulated in plants infected with phytoplasma, but not severely in those infested by insect vectors and variation in expression was found in genes involved in methylation. These results also showed that genes particularly orthologous to Arabidopsis APETALA3 involved in petal formation and flower development was down-regulated severely in phytoplasma-infected brassica and with the fact that phytoplasma and insect induce variation in developmental gene expression. The DNA methylation status of flower developmental gene in phytoplasma infected plants with 5-azacytidine restored gene expression strongly suggesting that DNA methylation was involved in down-regulation of floral development genes in phytoplasma infected brassica.

Keywords: genes expression, phytoplasma, DNA methylation, flower development

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Authors: Sérgio J. Teixeira, João J. Ferreira

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Tourism frequently gets identified as one of the sectors with the greatest potential for expansion on a global scale and hence conveying the importance of attempting to better understand the regional factors of competitiveness prevailing in this sector. This study’s objective essentially strives to provide a mapping of the scientific publications and the intellectual knowledge therein contained while conveying past research trends and identifying potential future lines of research in the fields of regional competitiveness and tourism innovation. This correspondingly deploys a systematic review of the literature in keeping with the bibliometric approach based upon VOSviewer software, with a particular focus on drafting maps for visualising the underlying intellectual structure. This type of analysis encapsulates the number of articles published and their annual number of citations for the period between 1900 and 2016 as registered by the Web of Science database. The results demonstrate how the intellectual structure on regional competitiveness divides essentially into three major categories: regional competitiveness, tourism innovation, and tourism clusters. Thus, the main contribution of this study arises out of identifying the main research trends in this field and the respective shortcomings and specific needs for future scientific research in the field of regional competitiveness and innovation in tourism.

Keywords: regional competitiveness, tourism cluster, bibliometric studies, tourism innovation, systematic review

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Authors: Ishani Majumdar, Jaishree Paul

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Introduction: Ulcerative Colitis (UC) is an inflammatory disease of the colon resulting from an autoimmune response towards individual’s own microbiota. Excessive inflammation is characterized by hyper-activation of NFkB, a transcription factor regulating expression of various pro-inflammatory genes. The ubiquitin editing complex consisting of TNFAIP3, ITCH, RNF11 and TAX1BP1 maintains homeostatic levels of active NFkB through feedback inhibition and assembles in response to various stimuli that activate NFkB. TNFAIP3 deubiquitinates key signaling molecules involved in NFkB activation pathway. ITCH, RNF11 and TAX1BP1 provide substrate specificity, acting as adaptors for TNFAIP3 function. Aim: This study aimed to find expression of members of the ubiquitin editing complex at the transcript level in inflamed colon tissues of UC patients. Materials and Methods: Colonic biopsy samples were collected from 30 UC patients recruited at Department of Gastroenterology, AIIMS (New Delhi). Control group (n= 10) consisted of individuals undergoing examination for functional disorders. Real Time PCR was used to determine relative expression with GAPDH as housekeeping gene. Results: Expression of members of the ubiquitin editing complex was significantly altered during active disease. Expression of TNFAIP3 was upregulated while concomitant decrease in expression of ITCH, RNF11, TAX1BP1 was seen in UC patients. Discussion: This study reveals that increase in expression of TNFAIP3 was unable to control inflammation during active UC. Further, insufficient upregulation of ITCH, RNF11, TAX1BP1 may limit the formation of the ubiquitin complex and contribute to pathogenesis of UC.

Keywords: altered expression, inflammation, ubiquitin editing complex, ulcerative colitis

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Authors: Samara E., Kilintzis P., Katsoras E., Martinidis G.

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Regions play an important role in the global economy by driving research and innovation policies through a major tool, the Regional Innovation System (RIS). RIS is a social system that encompasses the systematic interaction of the various organizations that comprise it in order to improve local knowledge and innovation. This article describes the methodological framework for developing and validating a RIS model utilizing system dynamics. This model focuses on the functional structure of the RIS, separating it in six diverse, interacting sub-systems.

Keywords: innovations, regional development, systems thinking, social system

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Authors: Cangul Altundas Akcay

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With the beginning of the mass movement called as the Arab Uprising, Middle Eastern politics has demonstrated an influential shift which has been threatening the existence of the ruling regimes. In this environment, in particular, regional powers have desired to control regional politics, and to expand their regional influence. Bearing that in mind, Turkey and Iran, two significant regional powers, have engaged in competition so as to affect the shifted regional geopolitics. In this context, this paper aims to investigate how regional powers, especially non-Arab ones, have viewed each other in the Arab Uprising, whereby focusing on Turkish perspectives towards Iran. In other words, it will shed light on how Turkey has conducted foreign policy towards Iran during the Arab Uprising. To analyse this, Turkey’s ideological and identity politics towards Iran will be examined as one of its foreign policy approaches. The question is thus that how ideological and identity politics have determined Turkish foreign policy towards Iran in the Arab Uprising. To answer that, the Syrian civil war will be analysed as the case study in this qualitative study, hypothesising that Turkey, which has both Turkish identity and Sunni sect, has competed with Iran, which has both Farsi identity and Shia sect, over the Syrian civil war.

Keywords: Arab uprising, ideological and identity politics, Iran, Turkey, Syrian civil war

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Authors: Djehich Mohamed Yousri

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In this paper, we explore the extent to which states seek to promote regional foreign policy. More specifically, the analytical feasibility is to find out exactly what countries seek to export, and how they have used their relations and foreign policies to enhance cooperation with other countries. The first part discusses the development of regional interests and theoretical approaches that attempted to explain the push for regionalism in the field of foreign policy. The second part of the paper presents the motives and mechanisms through which states spread the idea of regionalism in making foreign policy. Finally, we assess the implications of regionalism for the nature and practice of foreign policy, particularly with regard to the gains or constraints to which various actors are exposed in their regional endeavors. We conclude with some considerations that indicate that strengthening regionalism has become an additional and real program in the field of foreign policy analysis.

Keywords: foreign policy, collective foreign policy, regionalization and foreign policy, regional foreign policy, foreign affairs

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Authors: Cuili Yang, Chengcao Sun, Ruilin Xue, Yongyong Xi, Liang Wang, Dejia Li

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Backgrounds: Previous studies showed that Sirt1 plays an important role in C2C12 myoblast cell proliferation, but the mechanism(s) involved in this process remains unclear. This work was undertaken to determine if Myostatin participates in the regulation of C2C12 proliferation by Sirt1. Methods: We administrated the Sirt1 activator resveratrol, inhibitor Nicotinamide (NAM) and Myostatin inhibitor SB431542 on C2C12 myoblast cells. Cell viability was evaluated by CCK8 assay. The expression of Sirt1 and MyoD were detected by qRT-PCR. Utilizing western blot to determinate the expression of myostatin, P107 and p-P107. Results: Our results showed that resveratrol promoted the proliferation of C2C12 myoblast cells, while NAM suppressed the proliferation of C2C12 myoblast cells; SB431542 promoted the proliferation of C2C12 myoblast cells and attenuated the inhibition effect of NAM on C2C12 myoblast cells proliferation; Resveratrol can significantly increase the expression of Sirt1 and MyoD, decrease the expression of Myostatin, while NAM can significantly down-regulate the expression of Sirt1, MyoD and the phosphorylation of P107(p-P107), but up-regulate the expression of Myostatin and the protein P107; SB431542 can significantly mitigate the effect of NAM on the expression of MyoD, P107, and p-P107. Conclusions: Taken together, these results indicate that Sirt1 promotes the proliferation of C2C12 myoblast cells via Myostatin signaling pathway.

Keywords: Sirt1, C2C12 cells, proliferation, myostatin signaling pathway

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Authors: Salman Akrokayan

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Synthetic cDNA (ScDNA) of granulocyte colony-stimulating factor (G-CSF) was constructed using a DNA synthesizer with the aim to increase its expression level. 5' end of the ScDNA of G-CSF coding region was modified by decreasing the GC content without altering the predicted amino acids sequence. The identity of the resulting protein from ScDNA was confirmed by the highly specific enzyme-linked immunosorbent assay. In conclusion, a synthetic G-CSF cDNA in combination with the recombinant DNA protocol offers a rapid and reliable strategy for synthesizing the target protein. However, the commercial utilization of this methodology requires rigorous validation and quality control.

Keywords: synthetic cDNA, recombinant G-CSF, cloning, gene expression

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Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu

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Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.

Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer

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Authors: Alexander A. Tokmakov

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Cell-free protein synthesis is widely used to synthesize recombinant proteins. It allows genome-scale expression of various polypeptides under strictly controlled uniform conditions. However, only a minor fraction of all proteins can be successfully expressed in the systems of protein synthesis that are currently used. The factors determining expression success are poorly understood. At present, the vast volume of data is accumulated in cell-free expression databases. It makes possible comprehensive bioinformatics analysis and identification of multiple features associated with successful cell-free expression. Here, we describe an approach aimed at identification of multiple physicochemical and structural properties of amino acid sequences associated with protein solubility and aggregation and highlight major correlations obtained using this approach. The developed method includes: categorical assessment of the protein expression data, calculation and prediction of multiple properties of expressed amino acid sequences, correlation of the individual properties with the expression scores, and evaluation of statistical significance of the observed correlations. Using this approach, we revealed a number of statistically significant correlations between calculated and predicted features of protein sequences and their amenability to cell-free expression. It was found that some of the features, such as protein pI, hydrophobicity, presence of signal sequences, etc., are mostly related to protein solubility, whereas the others, such as protein length, number of disulfide bonds, content of secondary structure, etc., affect mainly the expression propensity. We also demonstrated that amenability of polypeptide sequences to cell-free expression correlates with the presence of multiple sites of post-translational modifications. The correlations revealed in this study provide a plethora of important insights into protein folding and rationalization of protein production. The developed bioinformatics approach can be of practical use for predicting expression success and optimizing cell-free protein synthesis.

Keywords: bioinformatics analysis, cell-free protein synthesis, expression success, optimization, recombinant proteins

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Authors: Ali Bayram, Burak Uz, Ilhan Dolasik, Remzi Yiğiter

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The GABARAP (GABAA-receptor-associated protein) family consists of GABARAP, GABARAPL1 (GABARAP-like 1) and GABARAPL2 (GABARAP-like 2). GABARAPL1, like GABARAP, was described to interact with both GABAA receptor and tubulin, and to be involved in intracellular GABAA receptor trafficking and promoting tubulin polymerization. In addition, GABARAPL1 is thought to be involved in various physiological (autophagosome closure, regulation of circadian rhythms) and/or pathological mechanisms (cancer, neurodegeneration). Alzheimer’s disease (AD) is a progressive neuro degenerative disorder characterized with impaired cognitive functions. Disruption of the GABAergic neuro transmission as well as cholinergic and glutamatergic interactions, may also be involved in the pathogenesis of AD. GABARAPL1 presents a regulated tissue expression and is the most expressed gene among the GABARAP family members in the central nervous system. We, herein, conducted a study to investigate the GABARAPL1 mRNA expression levels in patients with AD. 50 patients with AD and 49 control patients were enrolled to the present study. Messenger RNA expression levels of GABARAPL1 were detected by real-time polymerase chain reaction. GABARAPL1 mRNA expression in AD / control patients was 0,495 (95% confidence interval: 0,404-0,607), p= 0,00000002646. Reduced activity of GABARAPL1 gene might play a role, at least partly, in the pathophysiology of AD.

Keywords: Alzheimer’s disease, GABARAPL1, mRNA expression, RT-PCR

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Authors: M. Sunitha, B. Nithyavani, Mathew Yohannan, S. Thiruvieni Balajji, M. A. Rathi, C. Arul Raj, P. Ragavendran, V. K. Gopalkrishnan

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Establishment of an early and reliable biomarker for ovarian carcinogenesis whose expression can be monitored through noninvasive techniques will enable early diagnosis of cancer. Carbonic anhydrases (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. In von Hippel-Lindau (VHL)-defective tumors, the cell surface transmembrane carbonic anhydrase (CA) CA XI and CA XII genes are overexpressed because of the absence of pVHL. These enzymes are involved in causing a hypoxia condition, thereby providing an environment for metastasis. Aberrant expression of the facilitative glucose transporter GLUT I is found in a wide spectrum of epithelial malignancies. Studying the mRNA expression of CA IX, CA XII and Glut I isozymes in ovarian cancer cell lines (OAW-42 and PA-1) revealed the expression of these hypoxia genes. Immunohistochemical staining of carbonic anhydrases was also performed in 40 ovarian cancer tissues. CA IX and CA XII were expressed at 540 bp and 520 bp in OAW42, PA1 in ovarian cancer cell lines. GLUT-1 was expressed at 325bp in OAW 42, PA1 genes in ovarian cancer cell lines. Immunohistochemistry revealed high to moderate levels of expression of these enzymes. The immuostaining was seen predominantly on the cell surface membrane. The study concluded that these genes CA IX, CA XII and Glut I are expressed under hypoxic condition in tumor cells. From the present results expression of CA IX, XII and Glut I may represent potential targets in ovarian cancer therapy.

Keywords: ovarian cancer, carbonic anhydrase IX, XII, Glut I, tumor markers

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Authors: Mohd Ali Abbas Zaidi, Meenu Sachdeva, Jonaki Sen

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In the vertebrate embryo, the forebrain anlagen develops from the anterior-most region of the neural tube which is the precursor of the central nervous system (CNS). The roof plate located at the dorsal midline region of the forebrain anlagen, acts as a source of several secreted molecules involved in patterning and morphogenesis of the forebrain. One such key morphogenetic event is the invagination of the forebrain roof plate which results in separation of the single forebrain vesicle into two cerebral hemispheres. Retinoic acid (RA) signaling plays a key role in this process. Blocking RA signaling at the dorsal forebrain midline inhibits dorsal invagination and results in the absence of certain key features of this region, such as thinning of the neuroepithelium and a lowering of cell proliferation. At present we are investigating the possibility of other signaling pathways acting in concert with RA signaling to regulate this process. We have focused on BMP signaling, which we found to be active in a mutually exclusive domain to that of RA signaling within the roof plate. We have also observed that there is a change in BMP signaling activity on modulation of RA signaling indicating an antagonistic relationship between the two. Moreover, constitutive activation of BMP signaling seems to completely inhibit thinning and partially affect invagination, leaving the lowering of cell proliferation in the midline unaffected. We are employing in-silico modeling as well as molecular manipulations to investigate the relative contribution if any, of regional differences in rates of cell proliferation and thinning of the neuroepithelium towards the process of invagination. We have found expression of certain cell adhesion molecules in forebrain roof-plate whose mRNA localization across the thickness of neuroepithelium is influenced by Bmp and RA signaling, giving regional rigidity to roof plate and assisting invagination. We also found expression of certain cytoskeleton modifiers in a localized small domains in invaginating forebrain roof plate suggesting that midline invagination is under control of many factors.

Keywords: bone morphogenetic signaling, cytoskeleton, cell adhesion molecules, forebrain roof plate, retinoic acid signaling

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Authors: Fitria D. Ayuningtyas, Anggraini Barlian

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Green turtle (Chelonia mydas) is one of TSD (Temperature-dependent Sex Determination, TSD) animals which sex is determined by the egg’s incubation temperature. GSD (Genotypic Sex Determination) homologous genes such as Wilms’ Tumor (Wt1) and Forkhead Box L2 (FoxL2) play a role in TSD animal sex determination process. Wt1 plays a role in both male pathway, as a transcription factor for Sf1 gene and in female pathway, as a transcription factor for Dax1. FoxL2 plays a role specifically in female sex determination, and known as transcriptional factor for Aromatase gene. Until now, research on the pattern of Wt1 and FoxL2 genes expression in C.mydas has not been conducted yet. The aim of this research is to know the pattern of Wt1 and FoxL2 genes expression in Mesonephros-Gonad (MG) complexes of Chelonia mydas embryos incubated in masculinizing temperature (MT) and feminizing temperature (FT). Eggs of C.mydas incubated in 3 different stage of TSP (Thermosensitive Period) at masculinizing temperature (26±10C, MT) and feminizing temperature (31±10C FT). Mesonefros-gonad complexes were isolated at Pre-TSP stage (FT at days 14th, MT at days 24th), TSP stage (FT at days 24th, MT at days 36th) and differentiated stage (FT at days 40th, MT at days 58th). RNA from mesonephros-gonad (MG) complexes were converted into cDNA by RT-PCR process, and the pattern of Wt1 and FoxL2 genes expression is analyzed by quantitative Real Time PCR (qPCR) method, β-actin gene is used as an internal control. The pattern of Wt1 gene expression in Pre-TSP stage was almost the same between MG complexes incubated at MT or FT, while TSP and differentiation stage, the pattern of Wt1 gene expression in MG complexes incubated at MT or FT was increased. Wt1 gene expression of MG complexes that incubated at FT was higher than at MT. There was a difference pattern between Wt1 gene expression in this research compared to the previous research in protein level. It could be assumed that the difference caused by post-transcriptional regulation mechanisms before mRNA of Wt1 gene translated into protein structure. The pattern of FoxL2 gene expression in Pre-TSP stage was almost the same between MG complexes that incubated at MT and FT, and increased in both TSP and differentiated stage. The FoxL2 gene expression in MG complexes that incubated in FT is higher than MT on TSP and differentiated stage. Based on the results of this research, it can be assumed that Wt1 and FoxL2 gene were expressed in MG complexes that incubated both at MT and FT since Pre-TSP stage. The pattern of Wt1 gene expression was increased in every stage of gonadal development, and so do the pattern of FoxL2 gene expression. Wt1 and FoxL2 gene expressions were higher in MG complexes incubated at FT than MT.

Keywords: chelonia mydas, FoxL2, gene expression, TSD, Wt1

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Authors: Debjyoti Bhakat, Indranil Mondal, Asish K. Mukhopadayay, Nabendu S. Chatterjee

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Enterotoxigenic Escherichia coli is one of the leading causes of diarrhea in infants and travelers in developing countries. Colonization factors play an important role in pathogenesis and are one of the main targets for Enterotoxigenic Escherichia coli (ETEC) vaccine development. However, ETEC vaccines had poorly performed in the past, as the prevalence of colonization factors is region-dependent. There are more than 25 classical colonization factors presently known to be expressed by ETEC, although all are not expressed together. Further, there are other multiple non-classical virulence factors that are also identified. Here the presence and expression of common classical and non-classical virulence factors were studied. Further studies were done on the expression of prevalent colonization factors in different strains. For the prevalence determination, multiplex polymerase chain reaction (PCR) was employed, which was confirmed by simplex PCR. Quantitative RT-PCR was done to study the RNA expression of these virulence factors. Strains negative for colonization factors expression were confirmed by SDS-PAGE. Among the clinical isolates, the most prevalent toxin was est+elt, followed by est and elt, while the pattern was reversed in the control strains. There were 29% and 40% strains negative for any classical colonization factors (CF) or non-classical virulence factors (NCVF) among the clinical and control strains, respectively. Among CF positive ETEC strains, CS6 and CS21 were the prevalent ones in the clinical strains, whereas in control strains, CS6 was the predominant one. For NCVF genes, eatA was the most prevalent among the clinical isolates and etpA for control. CS6 was the most expressed CF, and eatA was the predominantly expressed NCVF for both clinical and controlled ETEC isolates. CS6 expression was more in strains having CS6 alone. Different strains express CS6 at different levels. Not all strains expressed their respective virulence factors. Understanding the prevalent colonization factor, CS6, and its nature of expression will contribute to designing an effective vaccine against ETEC in this region of the globe. The expression pattern of CS6 also will help in examining the relatedness between the ETEC subtypes.

Keywords: classical virulence factors, CS6, diarrhea, enterotoxigenic escherichia coli, expression, non-classical virulence factors

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Authors: Valeri Arghutashvili, Mari Gogochuri

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Tourism industry development is one of the key priorities in Georgia, as it has positive influence on economic activities. Its contribution is very important for the different regions, as well as for the national economy. Benefits of the tourism industry include new jobs, service development, and increasing tax revenues, etc. The main aim of this research is to review and analyze the potential of the Georgian tourism industry with its long-term strategy and current challenges. To plan activities in a long-term development, it is required to evaluate several factors on the regional and on the national level. Factors include activities, transportation, services, lodging facilities, infrastructure and institutions. The major research contributions are practical estimates about regional tourism development which plays an important role in the integration process with global markets.

Keywords: regional tourism, tourism industry, tourism in Georgia, tourism benefits

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Authors: Marta Christina Suciu, Cristina Andreea Florea

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The purpose of this paper is to highlight the relevance of building smart cities in the context of regional development and to analyze the important factors that make a city smart. These cities could be analyzed through the perspective of environment quality, the socio-cultural condition, technological applications and innovations, the vitality of the economic environment and public policies. Starting with these five sustainability domains, we will demonstrate the hypothesis that smart cities are the engine of the regional development. The aim of this paper is to assess the implications of smart cities, in the context of sustainable development, analyzing the benefits of developing creative and innovative cities. Regarding the methodology, it is used the systemic, logical and comparative analysis of important literature and data, also descriptive statistics and correlation analysis. In conclusion, we will define a direction on the regional development and competitiveness increasing.

Keywords: creativity, innovation, regional development, smart city, sustainability, triple helix

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Authors: Jagdish S. Patel, Piyush Chudasama

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Context: Over-expression of P-glycoprotein (P-gp) plays critical role in absorption of many drug candidates which results into lower bioavailability of the drug. P-glycoprotein also over expresses in many pathological conditions like diabetes, affecting the drug therapy. Modulation of P-gp expression using inhibitors can help in designing novel formulation enhancing the bioavailability of the drug in question. Objectives: The main focus of the study was to develop advanced glycation end products (AGEs) induced P-gp over expression in Caco-2 cells. Curcumin, piperine and epigallocatechin gallate were used to evaluate their P-gp inhibitory action using combinatorial approach. Materials and methods: Methylglyoxal (MG) induced P-gp over expression was checked in Caco-2 cells using real time PCR. P-gp inhibitory effects of the phytochemicals were measured after induction with MG alone and in combination of any two compounds. Cytotoxicity of each of the phytochemical was evaluated using MTT assay. Results: Induction with MG (100mM) significantly induced the over expression of P-glycoprotein in Caco-2 cells after 24 hr. Curcumin, piperine and epigallocatechin gallate alone significantly reduced the level of P-gp within 6 hr of treatment period monitored by real time PCR. The combination of any two phytochemical also down regulated the expression of P-gp in cells. Combinations of Curcumin and epigallocatechin gallate have shown significant down regulation when compared with other two combinations. Conclusions: Combinatorial approach for down regulating the expression of P-gp, in pathological conditions like diabetes, has demonstrated promising approach for therapeutic purpose.

Keywords: p-glycoprotein, curcumin, piperine, epigallocatechin gallate, p-gp inhibition

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Authors: Beloulou Mohamed Lamine, Fedili Benamar, Meliani Walid, Chaid Dalila, Lamara Abdelhak

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Introduction: Post-surgical chronic pain (PSCP) is a pathological condition with a rather complex etiopathogenesis that extensively involves sensitization processes and neuronal damage. The neuropathic component of these pains is almost always present, with variable expression depending on the type of surgery. Objective: To assess the presumed beneficial effect of Regional Anesthesia-Analgesia Techniques (RAAT) on the development of post-surgical chronic neuropathic pain (PSCNP) in various surgical procedures. Patients and Methods: A comparative study involving 510 patients distributed across five surgical models (mastectomy, thoracotomy, hernioplasty, cholecystectomy, and major abdominal-pelvic surgery) and randomized into two groups: Group A (240) receiving conventional postoperative analgesia and Group B (270) receiving balanced analgesia, including the implementation of a Regional Anesthesia-Analgesia Technique (RAAT). These patients were longitudinally followed over a 6-month period, with postsurgical chronic neuropathic pain (PSCNP) defined by a Neuropathic Pain Score DN2≥ 3. Comparative measurements through univariate and multivariable analyses were performed to identify associations between the development of PSCNP and certain predictive factors, including the presumed preventive impact (protective effect) of RAAT. Results: At the 6th month post-surgery, 419 patients were analyzed (Group A= 196 and Group B= 223). The incidence of PSCNP was 32.2% (n=135). Among these patients with chronic pain, the prevalence of neuropathic pain was 37.8% (95% CI: [29.6; 46.5]), with n=51/135. It was significantly lower in Group B compared to Group A, with respective percentages of 31.4% vs. 48.8% (p-value = 0.035). The most significant differences were observed in breast and thoracopulmonary surgeries. In a multiple regression analysis, two predictors of PSCNP were identified: the presence of preoperative pain at the surgical site as a risk factor (OR: 3.198; 95% CI [1.326; 7.714]) and RAAT as a protective factor (OR: 0.408; 95% CI [0.173; 0.961]). Conclusion: The neuropathic component of PSCNP can be observed in different types of surgeries. Regional analgesia included in a multimodal approach to postoperative pain management has proven to be effective for acute pain and seems to have a preventive impact on the development of PSCNP and its neuropathic nature, particularly in surgeries that are more prone to chronicization.

Keywords: post-surgical chronic pain, post-surgical chronic neuropathic pain, regional anesthesia-analgesia techniques, neuropathic pain score DN2, preventive impact

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Authors: Manwendra Kumar Tripathi, Subhas Ganguly

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A few glass forming ability expressions in terms of characteristic temperatures have been proposed in the literature. Attempts have been made to correlate the expression with the critical diameter of the bulk metallic glass composition. However, with the advent of new alloys, many exceptions have been noted and reported. In the present approach, a genetic programming based code which generates an expression in terms of input variables, i.e., three characteristic temperatures viz. glass transition temperature (Tg), onset crystallization temperature (Tx) and offset temperature of melting (Tl) with maximum correlation with a critical diameter (Dmax). The expression evolved shows improved correlation with the critical diameter. In addition, the expression can be explained on the basis of time-temperature transformation curve.

Keywords: glass forming ability, genetic programming, bulk metallic glass, critical diameter

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Authors: Hongping Lu, Kelbinur Tursun, Yaru Li, Yu Zhang, Shunai Liu, Ming Han

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Objective: To investigate whether NS5ATP9 is involved in IL-6 mediated autophagy and the relationship between IL-6 and NS5ATP9 in liver cancer cells. Methods: 1. Detect the mRNA and protein levels of Beclin 1 after HepG2 cells were treated with or without recombinant human IL-6 protein. 2. Measure and compare of the changes of autophagy-related genes with their respective control, after IL-6 was silenced or neutralized with monoclonal antibody against human IL-6. 3. HepG2 cells were incubated with 50 ng/ml of IL-6 in the presence or absence of PDTC. The expression of NS5ATP9 was analyzed by Western blot after 48 h. 4. After NS5ATP9-silenced HepG2 cells had been treated with 50 ng/ml recombinant IL-6 protein, we detected the Beclin 1 and LC3B (LC3Ⅱ/Ⅰ) expression. 5. HepG2 cells were transfected with pNS5ATP9, si-NS5ATP9, and their respective control. Total RNA was isolated from cells and analyzed for IL-6. 6. Silence or neutralization of IL-6 in HepG2 cells which has been transfected with NS5ATP9. Beclin 1 and LC3 protein levels were analyzed by Western blot. Result: 1. After HepG2 were treated with recombinant human IL-6 protein, the expression of endogenous Beclin 1 was up-regulated at mRNA and protein level, and the conversion of endogenous LC3-I to LC3-II was also increased. These results indicated that IL-6 could induce autophagy. 2. When HepG2 cells were treated with IL-6 siRNA or monoclonal antibody against human IL-6, the expression of autophagy-related genes were decreased. 3. Exogenous human IL-6 recombinant protein up-regulated NS5ATP9 via NF-κB activation. 4. The expression of Beclin 1 and LC3B was down-regulated after IL-6 treated NS5ATP9-silenced HepG2 cells. 5. NS5ATP9 could reverse regulates IL-6 expression in HepG2 cells. 6. Silence or neutralization of IL-6 attenuates NS5ATP9-induced autophagy slightly. Conclusion: Our results implied that in HCC patients, maybe the higher level of IL-6 in the serum promoted the expression of NS5ATP9 and induced autophagy in cancer cells. And the over-expression of NS5ATP9 which induced by IL-6, in turn, increased IL-6 expression, further, promotes the IL-6/NS5ATP9-mediated autophagy and affects the progression of tumor. Therefore, NS5ATP9 silence might be a potential target for HCC therapy.

Keywords: autophagy, Hepatocellular carcinoma, IL-6, microenvironment, NS5ATP9

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Authors: Soo Dong Cho, In-Ohk Ouh, Byeong Sul Kang, Seyeon Park, In-Soo Cho, Jae Young Song

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An VP2 gene from the current prevalent CPV (Canine Parvovirus) strain (new CPV-2a) in the Republic of Korea was expressed in a baculovirus expression system. Genomic DNA was extracted from the isolate strain CPV-2a. The recombinant baculovirus, containing the coding sequences of VP2 with the histidine tag at the N-terminus, were generated by using the Bac-to-Bac system. For production of the recombinant VP2 proteins, SF9 cells were transfection into 6 wells. Propagation of recombinant baculoviruses and expression of the VP2 protein were performed in the Sf9 cell line maintained. The proteins were detected to Western blot anlaysis. CPV-2a VP2 was detected by Western blotting the monoclonal antibodies recognized 6x His and the band had a molecular weight of 65 KDa. We demonstrated that recombinant CPV-2a VP2 expression in baculovirus. The recombinant CPV-2a VP2 may able to development of specific diagnostic test and vaccination of against CPV2. This study provides a foundation for application of CPV2 on the development of new CPV2 subunit vaccine.

Keywords: baculovirus, canine parvovirus 2a, Dog, Korea

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Authors: R. I. You, C. L. Ho, M. S. Dai, H. M. Hung, S. F. Yen, C. S. Chen, T. Y. Chao

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Neutrophils are the most abundant innate immune cells to against invading microorganisms. Numerous data shown neutrophils have plasticity in response to physiological and pathological conditions. Tumor-associated neutrophils (TAN) exist in distinct types of tumor and play an important role in cancer biology. Different transcriptomic profiles of neutrophils in tumor and non-tumor samples have been identified. Several miRNAs have been recognized as regulators of gene expression in neutrophil, which may have key roles in neutrophil activation. However, the miRNAs expression patterns in TAN are not well known. To address this question, magnetic bead isolated neutrophils from tumor-bearing mice were used in this study. We analyzed production of reactive oxygen species (ROS) by luminol-dependent chemiluminescence assay. The expression of miRNAs targeting NADPH oxidase, ROS generation and autophagy was explored using quantitative real-time polymerase chain reaction. Our data suggest that tumor environment influence neutrophil develop to differential states of activation via miRNAs regulation.

Keywords: tumor-associated neutrophil, miRNAs, neutrophil, ROS

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Authors: Tasaduk Musood

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In the dynamic landscape of higher education, intra-regional migration within Kashmir represents a complex interplay of influential elements. This qualitative research study aims to explore and analyze the multifaceted factors that significantly shape the patterns and motivations driving students' migration within the region. The study employed a qualitative research approach. The research is carried out with a sample of 60 participants, consisting of 30 male and 30 female students selected from various higher education institutions in the Punjab region. Through self-structured interviews and thematic analysis, the research unravels the underlying drivers, aspirations, challenges, and opportunities that underpin the phenomenon of intra-regional migration in the Kashmiri higher education landscape. The results of this study are expected to offer valuable insights for policymakers, educational institutions, and stakeholders to better understand, address, and potentially enhance the experiences and outcomes of shareholders of students engaged in intra-regional mobility within Kashmir's higher education domain. This study's findings aim to contribute significantly to the existing body of knowledge surrounding intra-regional migration within Kashmir's higher education landscape, offering a nuanced understanding of the drivers behind student mobility. Ultimately, this research endeavors to facilitate more informed and effective decision-making in addressing the evolving dynamics of intra-regional migration in Kashmir's higher education sector.

Keywords: intra-regional migration, student migration patterns, student mobility, higher education, kashmir

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Authors: Syed Toqueer Akhter, Muhammad Muzaffar Abbas

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Conflicts in Pakistan are a result of a configuration of factors, which are directly related to the system of the state, the unstable regional setting, and the geo-strategic location of Pakistan at large. This paper examines the impact of regional conflict onto the socio-political sustainability of Pakistan. The magnitude of the spillover from a conflicted region is similar in size of the equivalent increase in domestic conflict. Pakistan has gone at war three times with India; the border with India is named as the tensest borderlines of the world. Disagreements with India and lack of dispute settlement mechanisms have negatively effected the peace in the region, influx of illegal weapons and refugees from Afghanistan as an outcome of 9/11 incidence, have exasperated the criticality of levels of internal conflict in Pakistan. Our empirical findings are based on the data collected on regional conflict levels, regional trade, global trade, comparative defence capabilities of the region in contrast to Pakistan and the government regime (Autocratic, Democratic) over 1972-2007. It has been proposed in this paper that the intent of domestic conflict is associated with the conflict in the region, regional trade, global trade and the government regime of Pakistan. The estimated model (OLS) implies that domestic conflict is effected positively and significantly with long term impact of conflict in the region. Also, if defence capabilities of the region are better than that of Pakistan it effects domestic conflict positively and significantly. Conflict in neighbouring countries are found as a source of domestic conflict in Pakistan, whereas the regional trade as well as type of government regimes in Pakistan lowered the intensity of domestic conflict significantly, while globalized trade imply risk of domestic conflict to be reduced but not significantly.

Keywords: conflict, regional trade, socio-politcal instability

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Authors: Yuhua Wang, Mu Li, Jinggen Liu

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Aim: To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning. Methods: Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously. Results: Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration. Conclusion: The VLS is likely to be critically involved in drug-seeking behavior. The NMDA and D1 receptor-dependent Arc expression is important in drug-seeking behavior.

Keywords: arc, mesocorticolimbic system, drug rewarding behavior, NMDA receptor

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Authors: Tettey Afi Pamela, Sotaro Fujii, Hidetoshi Saito, Kawaii Koichiro

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Introduction: Organisms employ adaptive mechanisms when faced with any stressor or risk of being wiped out. This has made it possible for them to survive in harsh environmental conditions such as increasing temperature, low pH, and anoxia. Some of the mechanisms they utilize include the expression of heat shock proteins, synthesis of cryoprotectants, and anhydrobiosis. Heat shock proteins (HSPs) have been widely studied to determine their involvement in stress tolerance among various organism, of which chironomid species have been no exception. We examined the survival and expression of genes encoding five (5) heat shock proteins (HSP70, HSP67, HSP60, HSP27, and HSP23) from Chironomus sulfurosus larvae reared from 1st instar at 25°C, 30°C, 35°C, and 40°C. Results: The highest survival rate was recorded at 30°C, followed by 25°C, then 35°C. Only a small percentage of C. sulfurosus survived at 40°C (14.5%). With regards to HSPs expression, some HSPs responded to an increase in high temperature. The relative expression levels were lowest at 30°C for HSP70, HSP60, HSP27, and HSP23. At 25°C and 40°C, HSP70, HSP67, HSP60, HSP27, and HSP23 had the highest expression. At 35°C, all had the lowest expression. Discussion: The expression of heat shock proteins varies from one species to another. We designated the genes HSP 70, HSP 67, HSP 60, HSP 27, and HSP 23 genes based on transcriptome analysis of C. sulfurosus. Our study can be termed as a long-heat shock study as C. sulfurosus was reared from the first instar to the fourth instar, and this might have led to a continuous induction of HSPs at 25°C. 40°C had the lowest survival but highest HSPs expression as C. sulfurosus larvae had to utilize HSPs for sustenance. These results and future high-throughput studies at both the transcriptome and proteome level will improve the information needed to predict the future geographic distribution of these species within the context of global warming.

Keywords: chironomid, heat shock proteins, high temperature, heat shock protein expression

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Authors: Qinghua Xing, Noha M. Mesbah, Haisheng Wang, Jun Li, Baisuo Zhao

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Droplet digital PCR (ddPCR) is being increasingly adopted for gene detection and quantification because of its higher sensitivity and specificity. According to previous observations and our lab data, it is essential to use endogenous reference genes (RGs) when investigating gene expression at the mRNA level under salt stress. This study aimed to select and validate suitable RGs for gene expression under salt stress using ddPCR. Six candidate RGs were selected based on the tandem mass tag (TMT)-labeled quantitative proteomics of Alkalicoccus halolimnae at four salinities. The expression stability of these candidate genes was evaluated using statistical algorithms (geNorm, NormFinder, BestKeeper and RefFinder). There was a small fluctuation in cycle threshold (Ct) value and copy number of the pdp gene. Its expression stability was ranked in the vanguard of all algorithms, and was the most suitable RG for quantification of expression by both qPCR and ddPCR of A. halolimnae under salt stress. Single RG pdp and RG combinations were used to normalize the expression of ectA, ectB, ectC, and ectD under four salinities. The present study constitutes the first systematic analysis of endogenous RG selection for halophiles responding to salt stress. This work provides a valuable theory and an approach reference of internal control identification for ddPCR-based stress response models.

Keywords: endogenous reference gene, salt stress, ddPCR, RT-qPCR, Alkalicoccus halolimnae

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Authors: Sawan Kumar Jangid

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The paper attempts to study various facets of urbanization and regional planning in the framework of the present conditions and future needs. Urbanization is a dynamic system in which development and changes are prominent features; which implies population growth and changes in the primary, secondary and tertiary sector in the economy. Urban population is increasing day by day due to a natural increase in population and migration from rural areas, and the impact is bound to have in urban areas in terms of infrastructure, environment, water supply and other vital resources. For the organized way of planning and monitoring the implementation of Physical urban and regional plans high-resolution satellite imagery is the potential solution. Now the Remote Sensing data is widely used in urban as well as regional planning, infrastructure planning mainly telecommunication and transport network planning, highway development, accessibility to market area development in terms of catchment and population built-up area density. With Remote Sensing it is possible to identify urban growth, which falls outside the formal planning control. Remote Sensing and GIS technique combined together facilitate the planners, in making a decision, for general public and investors to have relevant data for their use in minimum time. This paper sketches out the Urbanization modal for the future development of Urban and Regional Planning. The paper suggests, a dynamic approach towards regional development strategy.

Keywords: development, dynamic, migration, resolution

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Authors: Akiko Kondo, Akio Kondo

Abstract:

We are facing serious problems related to a long-term depopulation and an aging society with a falling birth rate in Japan. In this situation, we are suffering from a shortfall in human resources as well as a shortage of workforce in rural regions. In addition, we are struggling with a protracted economic slump and excess concentration of population in the Tokyo Metropolitan area. It is an urgent national issue to consider how to live in this country and what kind of structure of society and administration policy is needed. It is necessary to clarify people’s desire for their way of living and social assistance to be provided. The aim of this study is to clarify the characteristics of regional issues and the degree of their seriousness in local municipalities of Japan. We conducted a questionnaire survey about regional agenda in all local municipalities in Japan. We obtained responses concerning the degree of seriousness of regional issues and degree of importance of policies. Based on the data gathered from the survey, it is apparent that many local municipalities are facing an aging population and declining population. We constructed a model to analyze factors for declining population. Using the model, it was clarified that a population’s age structure, job opportunities, and income level affect the decline of population. In addition, we showed the way of the evaluation of the state of a local municipality.

Keywords: evaluation, local municipality, regional analysis, regional issue

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