Search results for: political expression

Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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Authors: Salina Yahya Saddik

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The present study is designed to demonstrate the Ovarian Surface Epithelial cells (OSE) Estrogen Receptor α (ERα) and Progesterone Receptor (PR) during pregnancy and estrous cycle in rat. Moreover, determination of the levels of plasma progesterone, estradiol, FSH and LH were also made. The levels of plasma progesterone, estradiol, FSH and LH concentrations were determined on days 7 (n=5), 14 (n=5), and 21(n=5) of pregnancy in three groups of rats and during the estrous cycle (n=5) using ELISA kit. Immunohistochemical method for PR and ERα expression was also made on the ovary. During pregnancy, FSH and LH remained low except at term when LH levels began to increase from 16 ng/ml to 47 ng/ml. Progesterone levels significantly exceeded estradiol values in all pregnant rats with a peak value of 202 ng/ml on day 14. Elevated progesterone levels were associated negatively with LH and estradiol levels during pregnancy. The levels of estradiol surged significantly on day 21. Immunohistochemistry of the ovary showed low levels of OSE cells staining positive for ERα expression. ERα positive cells were absent on day 7 and 14 of pregnancy, only day 21 recorded a very low percentage of immunostaining (0.5%) within the nuclei of OSE cells. On the contrary, immunostaining of PR was not observed within the nuclei of OSE cells in all groups of study. In conclusions, these results may suggest that progesterone effect during pregnancy seems to be overriding the positive effect of estrogens on OSE cells. High progesterone levels may have a direct negative effect on gonadotropin production and thereby it might inhibit events leading to both follicular development and OSE proliferation. Understanding the factors affecting OSE proliferation may help elucidating the mechanism(s) of assisted diseases such as ovarian cancer.

Keywords: ovarian surface, pregnancy, gonadotropins, steroids

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Authors: Hana Hanaee-Ahvaz, Monika Cserjan-Puschmann, Christopher Tauer, Gerald Striedner

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Incorporation of noncanonical amino acids (ncAA) into proteins has become an interesting topic as proteins featured with ncAAs offer a wide range of different applications. Nowadays, technologies and systems exist that allow for the site-specific introduction of ncAAs in vivo, but the efficient production of proteins modified this way is still a big challenge. This is especially true for 'hard-to-express' proteins where low yields are encountered even with the native sequence. In this study, site-specific incorporation of azido-ethoxy-carbonyl-Lysin (azk) into an anti-tumor-necrosis-factor-α-Fab (FTN2) was investigated. According to well-established parameters, possible site positions for ncAA incorporation were determined, and corresponding FTN2 genes were constructed. Each of the modified FTN2 variants has one amber codon for azk incorporated either in its heavy or light chain. The expression level for all variants produced was determined by ELISA, and all azk variants could be produced with a satisfactory yield in the range of 50-70% of the original FTN2 variant. In terms of expression yield, neither the azk incorporation position nor the subunit modified (heavy or light chain) had a significant effect. We confirmed correct protein processing and azk incorporation by mass spectrometry analysis, and antigen-antibody interaction was determined by surface plasmon resonance analysis. The next step is to characterize the effect of azk incorporation on protein stability and aggregation tendency via differential scanning calorimetry and light scattering, respectively. In summary, the incorporation of ncAA into our Fab candidate FTN2 worked better than expected. The quantities produced allowed a detailed characterization of the variants in terms of their properties, and we can now turn our attention to potential applications. By using click chemistry, we can equip the Fabs with additional functionalities and make them suitable for a wide range of applications. We will now use this option in a first approach and develop an assay that will allow us to follow the degradation of the recombinant target protein in vivo. Special focus will be laid on the proteolytic activity in the periplasm and how it is influenced by cultivation/induction conditions.

Keywords: degradation, FTN2, hard-to-express protein, non-canonical amino acids

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Authors: Mohd Adil, Rosina Khan, Danishuddin, Asad U. Khan

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The aim of this study was to evaluate the influence of the crude and active solvent fraction of Trachyspermum ammi on S. mutans cariogenicity, effect on expression of genes involved in biofilm formation and caries development in rats. GC–MS was carried out to identify the major components present in the crude and the active fraction of T. ammi. The crude extract and the solvent fraction exhibiting least MIC were selected for further experiments. Scanning electron microscopy was carried out to observe the effect of the extracts on S. mutans biofilm. Comparative gene expression analysis was carried out for nine selected genes. 2-Isopropyl-5-methyl-phenol was found as major compound in crude and the active fraction. Binding site of this compound within the proteins involved in biofilm formation was mapped with the help of docking studies. Real-time RT-PCR analyses revealed significant suppression of the genes involved in biofilm formation. All the test groups showed reduction in caries (smooth surface as well as sulcal surface caries) in rats. Moreover, it also provides new insight to understand the mechanism influencing biofilm formation in S. mutans. Furthermore, the data suggest the putative cariostatic properties of T. Ammi and hence can be used as an alternative medicine to prevent caries infection.

Keywords: bio-film, Streptococcus mutans, dental caries, bio-informatic

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Authors: Davit Shahnazaryan, Diogo Gomes, Mher Safaryan

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Many symbolic computations and manipulations required in the analysis of partial differential equations (PDE) or systems of PDEs are tedious and error-prone. These computations arise when determining conservation laws, entropies or integral identities, which are essential tools for the study of PDEs. Here, we discuss a new Mathematica package for the symbolic analysis of PDEs that automate multiple tasks, saving time and effort. Methodologies: During the research, we have used concepts of linear algebra and partial differential equations. We have been working on creating algorithms based on theoretical mathematics to find results mentioned below. Major Findings: Our package provides the following functionalities; finding symmetry group of different PDE systems, generation of polynomials invariant with respect to different symmetry groups; simplification of integral quantities by integration by parts and null Lagrangian cleaning, computing general forms of expressions by integration by parts; finding equivalent forms of an integral expression that are simpler or more symmetric form; determining necessary and sufficient conditions on the coefficients for the positivity of a given symbolic expression. Conclusion: Using this package, we can simplify integral identities, find conserved and dissipated quantities of time-dependent PDE or system of PDEs. Some examples in the theory of mean-field games and semiconductor equations are discussed.

Keywords: partial differential equations, symbolic computation, conserved and dissipated quantities, mathematica

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Authors: George McMillan

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This paper introduces the methodology to create a baseline equation for the philosophical and social sciences in the behavioral-political-economic-demographic sequence. The two major ideological political-economic philosophies (Hume-Smith and Marx-Engels) are systematized into competing integrated three dimensional behavioral-political-economic models. The paper argues that Hume-Smith’s empathy-sympathy behavioral assumptions are a sufficient starting point to create the integrated causal model sought by Tooby and Cosmides. The author then shows that the prerequisite advances in psychology and demographic studies now exist to generate the universal economic theory sought by von Neumann-Morgenstern and the integrated behavioral-economic method of Gintis—a psychological (i.e., behavioral) socio-economic model. By updating Hume-Smith’s work with a modern understanding of psychology, as presented by Fromm and others, a new integrated societal model as postulated by Harsanyi can be created that intertwines the social and psychological sciences. The author argues that this fundamentally psychology-based model also can serve as a baseline equation for all social sciences as desired by Kant and Mach, as well as the ahistorical (psychological) philosophic model noted by Husserl, Heidegger, Tillich, and Strauss. The author concludes with a discussion of the necessary next steps to generating a detailed model that fuses these disciplines.

Keywords: Unified Social Theory

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Authors: Rini Rahul, Manoj Kumar

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Cadmium (Cd) is a poisonous trace metal, which is responsible for excess reactive oxygen species generation (ROS) in plants, thereby adversely affecting their productivity and commercial potential. Ricinus communis (castor) is an industry-efficient non-edible bioenergy crop used for phytoremediation and re-vegetation. We have determined the total Cd content in castor genotypes and established a relationship between the Cd tolerance mechanism and physiological parameters like chlorophyll fluorescence, the total photosynthetic activity, chlorophyll and carotenoid content as well as ROS generation and malondialdehyde content. This study is an effort to comprehend the interrelation between Cd toxicity (control, 250 µM and 500 µM), proline, various ROS scavenging enzymes (anti-oxidative in nature), nicotianamine synthase (NAS) and Natural resistance-associated macrophage protein (NRAMP) gene. The antioxidant enzyme activity increased for WM hence conferring Cd toxicity in this genotype. RcNRAMP genes showed differential expression in GCH2 and WM genotypes; this can also be one of the reasons for Cd toxicity and sensitivity in WM and GCH2, respectively. The cause of pronounced Cd tolerance in WM leaves can be because of enhanced expression of RcNAS1, RcNAS2 and RcNAS3 genes. Our results demonstrate that there is an interrelation between Cd toxicity (control, 250 µM and 500 µM), proline, various ROS scavenging enzymes (anti-oxidative in nature), NAS and NRAMP gene.

Keywords: ricinus communis, cadmium, reactive oxygen species, nicotianamine synthase, NRAMP, malondialdehyde

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Authors: Juan Jose Filgueira, Daniela Londono-Serna, Liliana Maria Hoyos

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Carnation (Dianthus caryophyllus) is one of the most important products of exportation in the floriculture industry worldwide. Fusariosis is the disease that causes the highest losses on farms, in particular the one produced by Fusarium oxysporum f.sp. dianthi, called vascular wilt. Gene identification and metabolic routes of the genes that participate in the building of the plant response to Fusarium are some of the current targets in the carnation breeding industry. The techniques for the identifying of resistant genes in the plants, is the analysis of the transcriptome obtained during the host-pathogen interaction. In this work, we report the cell transcriptome of different varieties of carnation that present differential response from Fusarium oxysporum f.sp. dianthi attack. The cells of the different hybrids produced in the outbreeding program were cultured in vitro and elicited with the parasite in a dual culture. The isolation and purification of mRNA was achieved by using affinity chromatography Oligo dT columns and the transcriptomes were obtained by using Illumina NGS techniques. A total of 85,669 unigenes were detected in all the transcriptomes analyzed and 31,000 annotations were found in databases, which correspond to 36.2%. The library construction of genic expression techniques used, allowed to recognize the variation in the expression of genes such as Germin-like protein, Glycosyl hydrolase family and Cinnamate 4-hydroxylase. These have been reported in this study for the first time as part of the response mechanism to the presence of Fusarium oxysporum.

Keywords: Carnation, Fusarium, vascular wilt, transcriptome

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Authors: Ahmed Bahieldin, Ahmed Atef, Jamal S. M. Sabir, Nour O. Gadalla, Sherif Edris, Ahmed M. Alzohairy, Nezar A. Radhwan, Mohammed N. Baeshen, Ahmed M. Ramadan, Hala F. Eissa, Sabah M. Hassan, Nabih A. Baeshen, Osama Abuzinadah, Magdy A. Al-Kordy, Fotouh M. El-Domyati, Robert K. Jansen

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Wild salt-tolerant barley (Hordeum spontaneum) is the ancestor of cultivated barley (Hordeum vulgare or H. vulgare). Although the cultivated barley genome is well studied, little is known about genome structure and function of its wild ancestor. In the present study, RNA-Seq analysis was performed on young leaves of wild barley treated with salt (500 mM NaCl) at four different time intervals. Transcriptome sequencing yielded 103 to 115 million reads for all replicates of each treatment, corresponding to over 10 billion nucleotides per sample. Of the total reads, between 74.8 and 80.3% could be mapped and 77.4 to 81.7% of the transcripts were found in the H. vulgare unigene database (unigene-mapped). The unmapped wild barley reads for all treatments and replicates were assembled de novo and the resulting contigs were used as a new reference genome. This resultedin94.3 to 95.3%oftheunmapped reads mapping to the new reference. The number of differentially expressed transcripts was 9277, 3861 of which were uni gene-mapped. The annotated unigene- and de novo-mapped transcripts (5100) were utilized to generate expression clusters across time of salt stress treatment. Two-dimensional hierarchical clustering classified differential expression profiles into nine expression clusters, four of which were selected for further analysis. Differentially expressed transcripts were assigned to the main functional categories. The most important groups were ‘response to external stimulus’ and ‘electron-carrier activity’. Highly expressed transcripts are involved in several biological processes, including electron transport and exchanger mechanisms, flavonoid biosynthesis, reactive oxygen species (ROS) scavenging, ethylene production, signaling network and protein refolding. The comparisons demonstrated that mRNA-Seq is an efficient method for the analysis of differentially expressed genes and biological processes under salt stress.

Keywords: electron transport, flavonoid biosynthesis, reactive oxygen species, rnaseq

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Authors: Sonam Kumari

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Tuberculosis is the deadliest disease worldwide. Millions of people lose their lives every year due to this disease. It has turned lethal due to the erratic nature of its causative organism, Mycobacterium tuberculosis (Mtb). Mtb tends to enter into an inactive, dormant state and emerge to replicating state upon encountering favorable conditions. The mechanism by which Mtb switches from the dormant state to the replicative form is still poorly characterized. Proteome studies have given us an insight into the role of certain proteins in giving stupendous virulence to Mtb, but numerous dotsremain unconnected and unaccounted. The WhiB family of proteins is one such protein that is associated with developmental processes in actinomycetes. Mtb has seven such proteins (WhiB1 to WhiB7). WhiB proteins are transcriptional regulators; they regulate various essential genes of Mtbby binding to their promoter DNA. Biophysical parameters of the effect of DNA binding on WhiB proteins has not yet been appropriately characterized. Interaction with DNA induces conformational changes in the WhiB proteins, confirmed by steady-state fluorescence and circular dichroism spectroscopy. ITC has deduced thermodynamic parameters and the binding affinity of the interaction. Since these transcription factors are highly unstable in vitro, their stability and solubility were enhanced by the co-expression of molecular chaperones. The present study findings help determine the conditions under which the WhiB proteins interact with their interacting partner and the factors that influence their binding affinity. This is crucial in understanding their role in regulating gene expression in Mtbandin targeting WhiB proteins as a drug target to cure TB.

Keywords: mycobacterium tuberculosis, TB, whiB proteins, ITC

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Authors: Alina Beraudi, Simona Catalani, Dalila De Pasquale, Eva Bianconi, Umberto Santoro, Susanna Stea, Pietro Apostoli

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Recently the European Community, in line with the international scientific community such as with the Consensus Statement, has determined to stop the use of metal-on-metal big head stemmed hip prosthesis. Among the factors accounted as responsible for the high failure rates of these hip implants are the release and accumulation of metal ions. Many studies have correlated the presence of these ions, besides other factors, with the induction of oxidative stress response. In our study on 12 subjects, we observed the patient specific capability to eliminate metal ions after revision surgery. While for cobalt all the patients were able to completely excrete cobalt ions within 5-7 months after metal-on-metal bearing removal, for chromium ions it didn’t happen. If on the one hand the toxicokinetic differences between the two types of ions are confirmed by toxicological and occupational studies, on the other hand, this peculiar way of exposition represents a novel and important point of view. Thus, two different approaches were performed to better understand the subject specific capability to transport metal ions (albumin study) and to manage the response to them (heme-oxygenase-1 study): - a mutational screening of ALBUMIN gene was conducted in 30 MoM prosthetic patients resulting in the absence of nucleotidic changes compared with the ALB reference sequence. To this study was also added the analysis of expression of modified albumin protein; - a gene and protein expression study on 44 patients of heme-oxygenase-1, that is one of the most important antioxidant enzyme induced by metallic ions, was performed. This study resulted in no statistically significant differences in the expression of the gene and protein heme-oxygenase-1 between prosthetic and non-prosthetic patients, as well as between patients with high and low ions levels. Our results show that the protein studied (albumin and heme-oxygenase-1) seem to be not involved in determining chromium and cobalt ions level. On the other hand, achromium and cobalt elimination rates are different, but similar in all patients analyzed, suggesting that this process could be not patient-related. We support the importance of researching more about ions transport within the organism once released by hip prosthesis, about the chemical species involved, the districts where they are contained and the mechanisms of elimination, not excluding the existence of a subjective susceptibility to these metals ions.

Keywords: chromium, cobalt, hip prosthesis, individual susceptibility

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Authors: Mehdi Nasr-Esfahani, Leila Mohammad Bagheri, Ava Nasr-Esfahani

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Root and collar rot disease caused by Phytophthora capsici (Leonian) is one of the most serious diseases in pepper, Capsicum annuum L. In this study, a diverse collection of 37 commercial edible and ornamental pepper genotypes infected with P. capsici were investigated for biomass parameters and enzymatic activity of peroxidase or peroxide reductases (EC), superoxide dismutase (SOD), polyphenol oxidase (PPOs), catalase (CAT) and phenylalanine ammonia-lyase (PAL). Seven candidate DEG genes were also evaluated on resistant and susceptible pepper cultivars, through measuring product formation, using spectrophotometry and real-time polymerase chain reaction. All the five enzymes and seven defense-gene candidates were up-regulated in all inoculated pepper accessions to P. capsici. But, the enzymes and DEG genes were highly expressed in resistant cv. 19OrnP-PBI, 37ChillP-Paleo, and “23CherryP-Orsh". The expression level of enzymes were 1.5 to 5.6-fold higher in the resistant peppers, than the control non-inoculated genotypes. Also, the transcriptional levels of related candidate DEG genes were 3.16 to 5.90-fold higher in the resistant genotypes. There was a direct and high correlation coefficient between resistance, bio-mass parameters, enzymatic activity, and resistance gene expression. The related enzymes and candidate genes expressed herein will provide a basis for further gene cloning and functional verification studies, and also will aid in an understanding of the regulatory mechanism of pepper resistance to P. capsici.

Keywords: AP2/ERF, cDNA, enzymes, MIP gene, q-RTPCR, XLOC

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Yaroslav Alexandrovich Levin

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In modern research on the history of the United States in World War II, it is quite popular to study the opposition of the American special services and, in particular, the Federal Bureau of Investigation (FBI) to various organizations of the German diasporas in new historical conditions. The appeal to traditional methods of historical research, comparative studies, and the principles of historicism will make it possible to more accurately trace the process of tightening the counterintelligence work of the Bureau and the close connection of concerns about the involvement of public organizations in the intelligence activities of the enemy. The broadcast of nationalist ideas by various communities of Germans under the auspices of their governments quickly attracted the attention of the FBI, which is in the process of consolidating its powers as the main US counterintelligence service. At the same time, the investigations and trials conducted by the John Edgar Hoover Department following these investigations often had an openly political color and increasingly consolidated the beginning of a political investigation in this service. This practice and its implementation ran into a tough contradiction between the legal norms of America, which proclaimed "democratic values," the right to freedom of speech, and the need to strengthen the internal security of the state and society in wartime. All these processes and the associated nuances and complexities are considered in specific examples of the work of federal agents against various pro-German organizations in the period 1941-45.

Keywords: World War II, internal security, countering extremism, counterintelligence, political investigation, FBI

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Authors: Sina Mahdavi

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Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human immunodeficiency virus (HIV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on human HIV infection in MS disease progression. In this study, the keywords "Multiple sclerosis", "Human immunodeficiency virus ", and "Central nervous system" in the databases PubMed, and Google Scholar between 2017 and 2022 were searched and 15 articles were chosen, studied, and analyzed. Revealed histologic signs of "MS-like illness" in the setting of HIV, which comprised widespread demyelination with reactive astrocytes, foamy macrophages, and perivascular infiltration with inflammatory cells, all of which are compatible with MS lesions. Human immunodeficiency virus causes dysfunction of the immune system, especially characterized by hypergammaglobulinemia and chronic activation of B cells. Activation of B cells leads to increased synthesis of immunoglobulin and finally to an excess of free light chains. Free light chains may be involved in autoimmune responses against neurons. There is a high expression of HIV during the course of MS, which indicates the relationship between HIV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HIV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human immunodeficiency virus, central nervous system, autoimmunity

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Authors: Michael A. Genovese

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The struggle for LGBTQ rights in the United States began in Greenwich Village, New York, in 1967, when police tried to break up a gathering of mostly gay men who were partying at the Stonewall Bar in NYC. As unlikely as it may sound, this “riot” proved to be consequential in raising the political consciousness of gay men in America. From that point on, gays engaged in a political battle to achieve the rights to which they were entitled. This essay examines changes in popular opinion regarding LGBTQ rights from the late 1960s through the Trump administration, and examines the role public pressure played on presidential politics. For most of this period, presidents “followed” public opinion. This was true even during the administration of Barack Obama when gay Americans finally achieved some clearly spelled out rights (e.g. same-sex marriage). The findings of this paper call into question certain assumptions about presidential leadership, and underline the power of public opinion in shaping policy.

Keywords: presidential leadership, gay rights, LGBTQ, popular opinion

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Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi

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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.

Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation

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Authors: Viviane A. O. Silva, Angela M. Costa, Glaucia N. M. Hajj, Ana Preto, Aline Tansini, Martin Roffé, Peter Jordan, Rui M. Reis

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Autophagy is a recycling and degradative system suggested to be a major cell death pathway in cancer cells. Autophagy pathway is interconnected with the endocytosis pathways sharing the same ultimate lysosomal destination. Lysosomes are crucial regulators of cell homeostasis, responsible to downregulate receptor signalling and turnover. It seems highly likely that derailed endocytosis can make major contributions to several hallmarks of cancer. WNK2, a member of the WNK (with-no-lysine [K]) subfamily of protein kinases, had been found downregulated by its promoter hypermethylation, and has been proposed to act as a specific tumour-suppressor gene in brain tumors. Although some contradictory studies indicated WNK2 as an autophagy modulator, its role in cancer cell death is largely unknown. There is also growing evidence for additional roles of WNK kinases in vesicular traffic. Aim: To evaluate the role of WNK2 in autophagy and endocytosis on glioma context. Methods: Wild-type (wt) A172 cells (WNK2 promoter-methylated), and A172 transfected either with an empty vector (Ev) or with a WNK2 expression vector, were used to assess the cellular basal capacities to promote autophagy, through western blot and flow-cytometry analysis. Additionally, we evaluated the effect of WNK2 on general endocytosis trafficking routes by immunofluorescence. Results: The re-expression of ectopic WNK2 did not interfere with autophagy-related protein light chain 3 (LC3-II) expression levels as well as did not promote mTOR signaling pathway alteration when compared with Ev or wt A172 cells. However, the restoration of WNK2 resulted in a marked increase (8 to 92,4%) of Acidic Vesicular Organelles formation (AVOs). Moreover, our results also suggest that WNK2 cells promotes delay in uptake and internalization rate of cholera toxin B and transferrin ligands. Conclusions: The restoration of WNK2 interferes in vesicular traffic during endocytosis pathway and increase AVOs formation. This results also suggest the role of WNK2 in growth factor receptor turnover related to cell growth and homeostasis and associates one more time, WNK2 silencing contribution in genesis of gliomas.

Keywords: autophagy, endocytosis, glioma, WNK2

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Authors: Ovidiu Anemtoaicei

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This paper offers a possible answer to the question of what it means to think about men and masculinities through the philosophy of sexual difference as developed by Luce Irigaray, employing Gilles Deleuze’s concept of 'critique' and arguing, at the same time, for a concept of 'becoming-man' as an expression of this answer. First, while examining the nature of the role of male bodies underlying the theorizing of men and masculinities in the field of the Critical Studies of Men and Masculinities, the paper argues for a turn to sexual difference theory as an answer to the 'gap' between the representations on male bodies and their participation in thought and masculine subjective production. Secondly, sharing Luce Irigaray’s critique of Western thought, the paper explores alternative morphological bodily 'locations' for rethinking male imaginary in relation to male embodiments, on the one hand, and in relation to the maternal and the feminine, on the other hand. Thirdly, the paper develops the idea that a phenomenologically-influenced approach towards male bodies might be productive, especially when thought through Irigaray’s sexual difference as a relational and experiential ontology. Finally, while showing that Irigaray and Deleuze share a similar critique of Western philosophical thought and of the masculine historical subject, it proposes a rethinking of the concept of 'becoming-man' as an assemblage meeting between Irigaray’s theory of sexual difference and Deleuze and Guattari’s nomadologic project, as a possibility of thinking change in men’s masculine subjective constitution in relation to both women and other men. As far as the ethical implications of such rethinking are concerned, the paper urges for the cultivation of a masculine culture of stepping back and its constitutive political, social and cultural practices so as to make possible the construction of new spaces that would allow for the becoming of at least two subjects based on the respect for their differences.

Keywords: feminist philosophy, male bodies, masculinities, phenomenology, sexual difference

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Authors: Sarthak S. Salunke

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Development, as a notion, is seen in perspective of western philosophical conceptions, and the western developed nations have become a yardstick for setting up development goals for developing and underdeveloped nations around the world. This blanket term of development becomes superficial and materialistic in context of the vast geopolitical, territorial, cultural and behavioral diversities existing in countries of the Africa and the Asia, and tends to undermine the atomistic aspect of development. Indian political theories, which are often seen as religious philosophies, have inherent structure of development of human being as an individual and as a part of the society, and, in result, development of the State. These theories, primarily individualistic in nature, have a combination of altruism and rationalism which guides human beings towards constructing a collectively developed and morally sustainable society. This research focuses on the application of this Indian thought in combination of classical liberal thought to tackle the issues of development in diverse societies. The proposed restructured model of development is based on molecular individualism, instead of atomic individual approach of liberalists, which lets development modelers to target meaningful clusters for designating goals for development based on the particular needs based on geopolitical, cultural and ethical requirements, and making it meaningful in conjunction with global development to establish a harmony between western and eastern worlds.

Keywords: Indian political thought, development, liberalism, molecular individualism

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Authors: Uğur Tuztaşi, Mehmet Uysal, Yavuz Arat

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The tomb (grave) structures that have influenced the architectural culture from the Seljuk times to the Ottoman throughout Anatolia are members of a continuing building tradition in terms of monumental expression and styles. This building typology which has religious and cultural permeability in view of spatial traces and structural formations follows the entire trajectory of the respect to death and the deceased from the Seljuks to the Ottomans and also the changing burial traditions epitomised in the form of mausoleums in the Turkish Republic. Although the cultural layers have the same contents with regards to the cult of monument this architectural tradition which evolved from tombs to mausoleums changed in both typological formation and structural size. In short, the tomb tradition with unique examples of architectural functions and typological formations has been encountered from 13th century onwards and continued during the Ottoman period with changes in form and has transformed to mausoleums during the 20th century. This study analyses the process of transformation from complex structures to simple structures and then to monumental graves in terms of architectural expression. Moreover, the study interrogates the architectural language of Anatolian Seljuk tombs to Ottoman tombs and monumental graves built during the republican period in terms of spatial and structural contexts.

Keywords: death and space in Turks, monumental graves, language of architectural style, morphological transformations

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Authors: Hugh Byrd, Steve Matthewnan

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The devastation of the city centre of Christchurch, New Zealand, after the 2010 and 2011 earthquakes presented an opportunity to rebuild infrastructure in a coordinated and efficient manner to allow for a city that was energy efficient, low carbon, resilient and provided both energy security and justice. The research described in this paper records the processes taken to attempt to rebuild the energy infrastructure. The story is one of political decisions overriding appropriate technology and ultimately is a lesson in how not to handle the implementation of post-disaster energy infrastructure. Lack of clarity in decision making by central government and then not pursuing consultant’s recommendations led to a scheme that was effectively abandoned in 2016 and described as ‘a total failure’. The paper records the critical events that occurred and explains why the proposed energy infrastructure was both politically and technologically inappropriate.

Keywords: energy infrastructure, policy and governance, post-disaster rebuilding

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Authors: Omaima A. Sharaf, Wafaa M. Abd El-Rahim, Hassan Moawad, Michael J. Sadowsky

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Textile industry is one of the important industries in the worldwide. It is known that the eco-friendly industrial and agricultural activities are significant for socio-economic stability of all countries. The absence of appropriate industrial waste water treatments is essential barrier for sustainable development in food and agricultural sectors especially in developing country like Egypt. Thus, the development of enzymatic bioremediation technology for textile dye removal will enhance the collaboration between scientists who develop the technology and industry where this technology will be implemented towards the safe disposal of the textile dye wastes. Highly efficient microorganisms are of most importance in developing and using highly effective biological treatment processes. Bacterial degradation of azo dyes is generally initiated by an enzymatic step that involves cleavage of azo linkages, usually with the aid of an azoreductase as electron donor. Thus, expanding the spectrum of microorganisms with high enzymatic activities as azoreductases and discovering novel azo-dye degrading enzymes, with enhanced stability and superior catalytic properties, are necessary for many environmental and industrial applications. Consequently, the use of molecular tools has become increasingly integrated into the understanding of enzyme properties and characterization. Researchers have utilized a gene cloning and expression methods as a tool to produce recombinant protein for decolorizing dyes more efficiently. Thus, presumptive evidence for the presence of genes encoding azoreductases in the genomes of selected local, and most potent azo-degrading strains were obtained by using specific oligonucleotides primers. These potent strains have been isolated from textile industrial wastewater in Egypt and identified using 16S rRNA sequence analysis as 'Lysinibacillus macrolidesB8, Brevibacillus parabrevisB11, Bacillus coagulansB7, and B. cereusB5'. PCR products of two full length genes designated as (AZO1;621bp and AZO2;534bp) were detected. BLASTx results indicated that AZO1 gene was corresponding to predicted azoreductase from of Bacillus sp. ABP14, complete genome, multispecies azoreductase [Bacillus], It was submitted to the gene bank by an accession no., BankIt2085371 AZO1 MG923210 (621bp; 207 amino acids). AZO1 was generated from the DNA of our identified strains Lysinibacillus macrolidesB8. On the other hand, AZO2 gene was corresponding to a predicted azoreductase from Bacillus cereus strain S2-8. Gene bank accession no. was BankIt2085839 AZO2 MG932081 (534bp;178 amino acids) and it was amplified from our Bacillus coagulansB7. Both genes were successfully cloned into pCR2.1TOPO (Invitrogen) and in pET28b+ vectors, then they transformed into E. coli DH5α and BL21(DE3) cells for heterologous expression studies. Our recombinant azoreductases (AZO1&AZO2) exhibited potential enzyme activity and efficiently decolorized an azo dye (Direct violet). They exhibited pH stability between 6 and 8 with optimum temperature up to 60°C and 37 °C after induction by 1mM and 1.5mM IPTG, for both AZO1 &AZO2, respectively. These results suggested that further optimization and purification of these recombinant proteins by using different heterologous expression systems will give great potential for the sustainable utilization of these recombinant enzymes in several industrial applications especially in wastewater treatments.

Keywords: azoreductases, decolorization, enzyme activity, gene cloning and expression

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Authors: Olga V. Chervyakova, Elmira T. Tailakova, Vitaliy M. Strochkov, Kulyaisan T. Sultankulova, Nurlan T. Sandybayev, Lev G. Nemchinov, Rosemarie W. Hammond

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Sheep pox is a highly contagious infection that OIE regards to be one of the most dangerous animal diseases. It causes enormous economic losses because of death and slaughter of infected animals, lower productivity, cost of veterinary and sanitary as well as quarantine measures. To control spread of sheep pox infection the attenuated vaccines are widely used in the Republic of Kazakhstan and other Former Soviet Union countries. In spite of high efficiency of live vaccines, the possible presence of the residual virulence, potential genetic instability restricts their use in disease-free areas that leads to necessity to exploit new approaches in vaccine development involving recombinant DNA technology. Vaccines on the basis of recombinant proteins are the newest generation of prophylactic preparations. The main advantage of these vaccines is their low reactogenicity and this fact makes them widely used in medical and veterinary practice for vaccination of humans and farm animals. The objective of the study is to produce recombinant immunogenic proteins for development of the high-performance means for sheep pox prophylaxis. The SPV proteins were chosen for their homology with the known immunogenic vaccinia virus proteins. Assay of nucleotide and amino acid sequences of the target SPV protein genes. It has been shown that four proteins SPPV060 (ortholog L1), SPPV074 (ortholog H3), SPPV122 (ortholog A33) and SPPV141 (ortholog B5) possess transmembrane domains at N- or C-terminus while in amino acid sequences of SPPV095 (ortholog А 4) and SPPV117 (ortholog А 27) proteins these domains were absent. On the basis of these findings the primers were constructed. Target genes were amplified and subsequently cloned into the expression vector рЕТ26b(+) or рЕТ28b(+). Six constructions (pSPPV060ΔТМ, pSPPV074ΔТМ, pSPPV095, pSPPV117, pSPPV122ΔТМ and pSPPV141ΔТМ) were obtained for expression of the SPV genes under control of T7 promoter in Escherichia coli. To purify and detect recombinant proteins the amino acid sequences were modified by adding six histidine molecules at C-terminus. Induction of gene expression by IPTG was resulted in production of the proteins with molecular weights corresponding to the estimated values for SPPV060, SPPV074, SPPV095, SPPV117, SPPV122 and SPPV141, i.e. 22, 30, 20, 19, 17 and 22 kDa respectively. Optimal protocol of expression for each gene that ensures high yield of the recombinant protein was identified. Assay of cellular lysates by western blotting confirmed expression of the target proteins. Recombinant proteins bind specifically with antibodies to polyhistidine. Moreover all produced proteins are specifically recognized by the serum from experimentally SPV-infected sheep. The recombinant proteins SPPV060, SPPV074, SPPV117, SPPV122 and SPPV141 were also shown to induce formation of antibodies with virus-neutralizing activity. The results of the research will help to develop a new-generation high-performance means for specific sheep pox prophylaxis that is one of key moments in animal health protection. The research was conducted under the International project ISTC # K-1704 “Development of methods to construct recombinant prophylactic means for sheep pox with use of transgenic plants” and under the Grant Project RK MES G.2015/0115RK01983 "Recombinant vaccine for sheep pox prophylaxis".

Keywords: prophylactic preparation, recombinant protein, sheep pox virus, subunit vaccine

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Authors: Piyush Bajpai, Sneha Pandey

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Mumbai’s Dhobighat, 150 year old largest open laundry in the world, is the true live-work place and only source of income for some of Mumbai’s highest density ‘urban poor’ residents. The regeneration of Dhobighat, due to its ultra prime location and complex socio-political culture has been a complex issue. This once flourishing urban industrial core has been degrading for the past several decades mainly due to the decline of the open laundry business, the site’s over burdened infrastructure and conflicting socio-political and economic forces. The phenomena of ‘exaptation’ or ‘co-option’ has been observed by evolutionary biologists as a process responsible for producing highly tenacious and resilient offsprings within a species. The reddish egret uses its wings to cast shadow in shallow waters to attract small fish and hunt them. An unrelated feature used opportunistically to produce a very favorable result. How can this idea of co-option be applied to resolve the complex issue of Dhobighat’s regeneration? Our paper proposes a new methodology/approach for the regeneration of Dhobighat through the lens of evolutionary biology. Forces and systems (social, political, economic, cultural and ecological) that seem conflicting or unrelated by nature are opportunistically transformed into symbiotic and complimentary relationships that produce an inclusive, resilient and holistic solution for the regeneration of Dhobighat.

Keywords: urban regeneration, exaptation, resilience, Dhobighat, Mumbai

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Authors: Clement Ndoricimpa

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The expression of stance is highly expected in writing at tertiary level. Through a selection of linguistic and rhetorical elements, writers express commitment, critical distance and build a critically discerning reader in texts. Despite many studies on patterns of stance in students’ academic writing, little may not be known about how English as a Foreign Language students learns to build a critically discerning reader in their texts. Therefore, this study examines patterns of stance in essays written by students majoring in business administration at English-medium University in Burundi as part of classroom assignments. It draws on systemic functional linguistics to analyze qualitatively and quantitatively the data. The quantitative analysis is used to identify the differences in frequency of stance patterns in the essays. The results show a significant difference in the use of boosters by lower- and upper-level students. Lower-level students’ writing contains more boosters and many idiosyncratic sentence structures than do upper-level students’ writing, and upper-level students’ essays contain more hedging and few grammatical mistakes than do lower-level students’ essays. No significant difference in the use of attitude markers and concessive and contrastive expressions. Students in lower- and upper-level do not use attitude markers and disclaimer markers appropriately and accurately. These findings suggest that students should be taught the use of stance patterns in academic writing.

Keywords: academic writing, metadiscourse, stance, student corpora

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Authors: Hyeon Sop Baek

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This paper will investigate the Korean concept of han and suggest that the feeling of han is essentially inseparable from the central project of the Korean neo-Confucian philosophical tradition. Han is a complex sentiment, but one may characterize it as an internally directed complex of sentiments of frustration, sadness, and anger. In particular, this paper aims to demonstrate that the Korean neo-Confucian project's ultimate objective was to build a pluralistic world – where different people can coexist together in harmony and participate in building the ideal world. Nevertheless, the confrontation between the neo-Confucian idea – that every person has the intrinsic potential to be moral – and the bleakness of reality that made their objective virtually impossible to achieve led to the formation and development of the feeling of han. The paper will first examine the concept of han and what it entails and then investigate the core elements of Korean neo-Confucianism, examining the works of Korean neo-Confucians, including Toegye, Yulgok, and Jeong Dojeon. Furthermore, the concept of plurality will be drawn from the political theory of Hannah Arendt. While the Arendtian and Korean neo-Confucian philosophies are ultimately different, this paper will contend that the two philosophies' broader aims share many resonating points. Specifically, within both philosophies, the human plurality – that all humans are equal but not the same – underlies the foundation of an ideal political realm. From there, an argument that the difficulty faced by the neo-Confucians in Korea in constructing a polity based on the ideal of respect and human moral capacity ultimately contributed to the emergence of the sentiment han will be presented. In conclusion, this paper will demonstrate that the ultimate objectives of Korean Confucianism lie in closing the gap between the ideal and reality in moral cultivation as well as its political project of building an ideal, pluralistic world, and han emerges from the realization of the difficulty of achieving that goal. Finally, this paper will contest that han needs not be perceived negatively, and han can be a driving force for political participation in the contemporary democratic, pluralistic society.

Keywords: Korea, Confucianism, neo-Confucianism, philosophy, han, Korean philosophy

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Authors: Gustavo Naranjo Maroto, Dolores Fernandez Martinez

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Context has always been essential to understand any reaction from every human being, and words, whether written or spoken, are definitely a powerful representative sample of human reaction. This study starts with an accurate breakdown of the context in which the current president of the US, Mr. Donald J. Trump is conveying his discourses in order to be able to judge them from a critical discourse analysis point of view. The present world’s scenario with a pandemic disease in form of Covid-19 that is threatening the world and certainly putting at risk the so called 'Welfare State', the role of the United States as the first superpower on earth nowadays, the very peculiar profile of President Trump not only as a politician but as a persona, and the fact of being on the verge of a very controversial presidential elections are without doubt a great and undeniable opportunity for the implementation of the critical discourse analysis methodology. Hence, this research will primarily analyze in detail some of the most interesting discourses delivered by Trump in different media since the very beginning of the outbreak of the coronavirus pandemic in the United States of America (February, 2020), sadly very often downplayed by President Trump, until the final result of the upcoming presidential election scheduled for Tuesday, November 3, 2020, where the political discourse has been dramatically downgraded to a very dangerous state, putting in jeopardy the fundamentals of the political fair play in terms of speech. Finally, the study will hopefully conclude with the final outcome of the data analyzed, allowing to picture how significant the context can be concerning linguistics on the one hand, in terms of shaping or altering the message that the issuer thought to convey in the first place, and on the other hand, generously assessing to what extend the recipients of the message are influenced by the message in terms of receptiveness.

Keywords: Covid-19, critical discourse analysis, Donald J. Trump, political discourse

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Authors: Rasha A. Salameh

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This research attempts to evaluate the treatment provided by the Qatari media to the decision to allow Saudi women to drive, and then activate this decision after a few months, that is, within the time frame between September 26, 2017 until June 30, 2018. This is through asking several questions, including whether the political dispute between Qatar and Saudi Arabia has cast a shadow over this handling, and if these Qatari media handlings are used to criticize the Saudi regime for delaying this step. Here emerges one of the research hypotheses that says that the coverage did not have the required professionalism, due to the fact that the decision and its activation took place in light of the political stalemate between Qatar and the Kingdom of Saudi Arabia, which requires testing the media framing and agenda theories to know to what extent they apply to this case. The research dealt with a sample of five Qatari media read in this sample: Al-Jazeera Net, The New Arab Newspaper, Al-Sharq Newspaper, The Arab Newspaper, and Al-Watan Newspaper. The results showed that most of the authors who covered the decision to allow Saudi women to drive a car did not achieve a balance in their writing, and that almost half of them did not have objectivity, and this indicates the proof of the hypothesis that there is a defect in the professional competence in covering the decision to allow Saudi women to drive cars by means of Qatari media, and the researcher attributes this result to the political position between Qatar and Saudi Arabia, in addition to the fact that the Arab media in most of them are characterized by a low ceiling of freedom, and most of them are identical in their position with the position of the regime’s official view.

Keywords: Saudi women, objectivity, hate speech, stereotype

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Authors: Diya Sarkar, Prafulla C. Mishra

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In a parliamentary system, party discipline is the impulse; when it falls short, the government usually falls. Conceivably, the platform of Indian politics suffers with innumerous practical disorders. The politics of defection is one such specie entailing gross miscarriage of fair conduct turning politics into a game of thrones (powers). This practice of political nomaditude can trace its seed in the womb of British House of Commons. Therein, if a legislator was found to cross the floor, the party considered him disloyal. In other words, the legislator lost his allegiance to his former party by joining another party. This very phenomenon, in practice has a two way traffic i.e. ruling party to the opposition party or vice versa. The democracies like USA, Australia and Canada were also aware of this fashion of swapping loyalties. There have been several instances of great politicians changing party allegiance, for example Winston Churchill, Ramsay McDonald, William Gladstone etc. Nevertheless, it is interesting to cite that irrespective of such practice of changing party allegiance, none of the democracies in the west ever desired or felt the need to legislatively ban defections. But, exceptionally India can be traced to have passed anti-defection laws. The politics of defection had been a unique popular phenomenon on the floor of Indian Parliamentary system gradually gulping the democratic essence and synchronization of the Federation. This study is both analytical and doctrinal, which tries to examine whether representative democracy has lost its essence due to political nomadism. The present study also analyzes the classical as well as contemporary pulse of floor crossing amidst dynastic politics in a representative democracy. It will briefly discuss the panorama of defections under the Indian federal structure in the light of the anti-defection law and an attempt has been made to add valuable suggestions to streamline remedy for the still prevalent political defections.

Keywords: constitutional law, defection, democracy, polarization, political anti-trust

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