Search results for: political expression

Authors: Daniela E. Marin, Cornelia Braicu, Gina C. Pistol, Roxana Cojocneanu-Petric, Ioana Berindan Neagoe, Mihail A. Gras, Ionelia Taranu

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Aristolochic acid (AA) is a carcinogenic, mutagenic, and nephrotoxic compound commonly found in the Aristolochiaceae family of plants. AA is frequently associated with urothelial carcinoma of the upper urinary tract in human and animals and is considered as being responsible for Balkan Endemic Nephropathy. The pig provides a good animal model because the porcine urological system is very similar to that of humans, both in aspects of physiology and anatomy. MicroRNA (miRNA) are small non-coding RNAs that have an impact on a wide range of biological processes by regulating gene expression at post-transcriptional level. The objective of this study was to analyze the miRNA profiling in the kidneys of AA intoxicated swine. For this purpose, ten TOPIGS-40 crossbred weaned piglets, 4-week-old, male and females with an initial average body weight of 9.83 ± 0.5 kg were studied for 28 days. They were given ad libitum access to water and feed and randomly allotted to one of the following groups: control group (C) or aristolochic acid group (AA). They were fed a maize-soybean-meal-based diet contaminated or not with 0.25mgAA/kg. To profile miRNA in the kidneys of pigs, microarrays and bioinformatics approaches were applied to analyze the miRNA in the kidney of control and AA intoxicated pigs. After normalization, our results have shown that a total of 5 known miRNAs and 4 novel miRNAs had different profiling in the kidney of intoxicated animals versus control ones. Expression of miR-32-5p, miR-497-5p, miR-423-3p, miR-218-5p, miR-128-3p were up-regulated by 0.25mgAA/kg feed, while the expression of miR-9793-5p, miR-9835-3p, miR-9840-3p, miR-4334-5p was down-regulated. The microRNA profiling in kidney of intoxicated animals was associated with modified expression of target genes as: RICTOR, LASP1, SFRP2, DKK2, BMI1, RAF1, IGF1R, MAP2K1, WEE1, HDGF, BCL2, EIF4E etc, involved in cell division cycle, apoptosis, cell differentiation and cell migration, cell signaling, cancer etc. In conclusion, this study provides new data concerning the microRNA profiling in kidney after aristolochic acid intoxications with important implications for human and animal health.

Keywords: aristolochic acid, kidney, microRNA, swine

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Authors: Akbarnejad Neda

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A foreign language acquisition occurs when we can tell a joke and understand it. Most jokes are told in slang and common language. In the process of foreign language acquisition, an autonomous learner try to learn the standard language. But there is a colossal divergence between the usage of the different types of language in society. Here, we investigate the french slang and common language and examine the accurate perception of their usage. We illuminate the slang language in the french literature that provide considerably different types of language for an autonomous learner. We provide furthermore evidence from the french novels that demonstrate properly the different types of language and give in one sentence its social meanings. For example, the famous Queneau expression « Doukipudonktant » present the impact of slang language in society. The characters in the novel transfer the slang and the common language and their accurate usages. We present that the language of the autonomous learner depends on the language of the text that is read. Because literature is a vehicle of the culture and the expression demonstrate their real significations and usage in the culture, slang and common language have a crucial role in the culture and all of them are manifested in the oral language.

Keywords: common language, french, humor, slang language

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Authors: Li Chen, Feng Zhang, Shizhong Zheng

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SaikosaponinD (SSD) is a major component of saikosaponins isolated from Bupleurumfalactum. Our current study was to examine the toxic effect of SSD on liver cells and explore the possible mechanism. The results demonstrated that SSD induced mouse liver injury and led to apoptosis in LO2 cells. HE staining and TUNEL analyses showed that SSD stimulated liver injury and hepatocyte apoptosis in vivo. Subsequent experiments showed that SSD down-regulated Bcl-2 but up-regulated Bax. In vitro, SSD-treated LO2 cells exhibited apparent down-regulated expression of p-p38. Moreover, PDGF-βR agonist PDGF-BB alone significantly upregulated p38 phosphorylation, while combined with SSD, p38 phosphorylation expression was reduced. Furthermore, shRNA-mediated PDGF-βR knockdown augmented the inactivation of p-p38 and Bcl2 but abrogated the activation of Bax, these results were more obvious when shRNA combined with SSD. These data indicated that SSD stimulated liver injury and apoptosis in hepatocytes and PDGF-βR /p38 pathway may be the potential mechanistic.

Keywords: saikosaponin D, hepatotoxicity, liver injury, apoptosis, platelet-derived growth factor-β receptor, p38

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Authors: Hussain Mustatab Wahedi, Sun You Kim

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Skin acts as a barrier against the harmful environmental factors. Integrity and timely recovery of the skin from injuries and harmful effects of radiations is thus very important. This study aimed to investigate the importance of Sirt1 in the recovery of skin from UVB-induced damage and cutaneous wounds by using natural and synthetic novel Sirt1 activators. Juglone, known as a natural Pin1 inhibitor, and NED416 a novel synthetic Sirt1 activator were checked for their ability to regulate the expression and activity of Sirt1 and hence photo-damage and wound healing in cultured skin cells (NHDF and HaCaT cells) and mouse model by using Sirt1 siRNA knockdown, cell migration assay, GST-Pulldown assay, western blot analysis, tube formation assay, and immunohistochemistry. Interestingly, Sirt1 knockdown inhibited skin cell migration in vitro. Juglone up regulated the expression of Sirt1 in both the cell lines under normal and UVB irradiated conditions, enhanced Sirt1 activity and increased the cell viability by reducing reactive oxygen species synthesis and apoptosis. Juglone promoted wound healing by increasing cell migration and angiogenesis through Cdc42/Rac1/PAK, MAPKs and Smad pathways in skin cells. NED416 upregulated Sirt1 expression in HaCaT and NHDF cells as well as increased Sirt1 activity. NED416 promoted the process of wound healing in early as well as later stages by increasing macrophage recruitment, skin cell migration, and angiogenesis through Cdc42/Rac1 and MAPKs pathways. So, both these compounds activated Sirt1 and promoted the process of wound healing thus pointing towards the possible role of Sirt1 in skin regeneration and wound healing.

Keywords: skin regeneration, wound healing, Sirt1, UVB light

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Authors: Valentina Piric, Maja Martinovic, Zoran Barac

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The application of marketing to the domain of politics has become relevant in recent times. With this article the authors wanted to explore the issue of the current political engagement among young people in Croatia. The question is what makes young people (age 18-30) politically active in young democracies such as that of the Republic of Croatia. Therefore, the objective of this study was to discover the real or hidden motivations behind the decision to actively participate in politics among young members of the two largest political parties in the country – the Croatian Democratic Union and the Social Democratic Party of Croatia. The study expected to find that the motivation for political engagement of young people is often connected with a possible achievement of individual goals and egoistic needs such as: self-acceptance, social success, financial success, prestige, reputation, status, recognition from the others etc. It was also expected that, due to the poor economic and social situation in the country, young people feel an increasing disconnection from politics. Additionally, the authors expected to find that there is a huge potential to engage young people in the political life of the country through a proper and more interactive use of marketing communication campaigns and social media platforms, with an emphasis on highly ethical motives of political activity and their benefits to society. All respondents included in the quantitative survey (sample size [N=100]) are active in one of the two largest political parties in Croatia. The sampling and distribution of the survey occurred in the field in September 2016. The results of the survey demonstrate that in Croatia, the way young people feel about politics and act accordingly, are in fact similar to what the theory describes. The research findings reveal that young people are politically active; however, the challenge is to find a way to motivate even more young people in Croatia to actively participate in the political and democratic processes in the country and to encourage them to see additional benefits out of this practice, not only related to their individual motives, but related more to the well-being of Croatia as a country and of every member of society. The research also discovered a huge potential for political marketing communication possibilities, especially related to interactive social media. It is possible that the social media channels have a stronger influence on the decision-making process among young people when compared to groups of reference. The level of interest in politics among young Croatians varies; some of them are almost indifferent, whilst others express a serious interest in different ways to actively contribute to the political life of the country, defining a participation in the political life of their country almost as their moral obligation. However, additional observations and further research need to be conducted to get a clearer and more precise picture about the interest in politics among young people in Croatia and their social potential.

Keywords: Croatia, marketing communication, motivation, politics, young people

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Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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Authors: Mahmood Seyyed, Akram Salehi Heykoei, Hamidreza Safakish Kashani

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Among the remaining resource of the past, coins considered as an authentic documents among the most important documentary sources. The coins were minted in a place that called mint. The number and position of the mints in each period reflects the amount of economic power, political security and business growth, which was always fluctuated its position with changing the political and economic condition. Considering that, trade has more growth during the Safavid period than previous ones, the mint also has been in greater importance. It seems the one hand, the growth of economic in Safavid period has a direct link with the number and places of the mints at that time and in the other hand, the mints have been formed in some places because of the specific characteristic of cities and regions. Increasing the number of mints in the north of the country due to the growth of silk trade and in the west and northwest due to the political and commercial relation with Ottoman Empire, also the characteristics such as existence of mines, located in the Silk Road and communication ways, all are the results of this investigation. Accordingly, in this article researcher tries to examine the characteristics that give priority to a city for having mint. With considering that in the various historical periods, the mints were based in the most important cities in terms of political and social, at that time, this article examines the cities specific characteristics in the formation of the mints in Safavid period.

Keywords: documentary sources, coins, mint, city, Safavid

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Authors: Khries Sawsan

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the phenomenon of urbanization is considered as one of the most important tourism resources that differ from one country to another and from one region to another in the same country. Our concern in tourism accommodation is explained by the fact that their location is directly related to the movement to tourist sites .Besides, these constructions comport security considered as the most important motivation for tourists in their choice of any destination. Hotels are the most representative expression of tourism. This is due to their physical prominence in the landscape and being the sole urban component totally unique to tourism. This study sheds light on the impact of tourism development on the spatial pattern in Jordan. It describes the linkages between existing tourism development policies and the spatial development patterns that have occurred as a result throughout Jordan, particularly looking at the impact that tourism has had on the physical environment of major tourism destinations. It puts an illustrative plan of the impact of the augmentation of tourism accommodations in Jordan in the past 40 years ago. The findings of this study help us to understand better the operation of Jordan’ dynamic changes in the location An intensive analysis is then applied on a representative case study in three regions: Amman, Petra and Aqaba. The study proceeds from an historical perspective to, show the evolution of the current development patterns an increase of tourism’s impact on spatial, in the presence of factors as political and economic stability, is expected.

Keywords: spatial patterns, urbanisation, spatial transformations, tourism planning, Jordan

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Authors: Hirowati Ali, Aisyah Ellyanti, Dewi Rusnita, Septelia Inawati Wanandi

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Stem cell has been known for its potency to be differentiated in many cells. Recently stem cell has been used for many treatment of degenerative medicine. It is still controversy whether stem cell can be used for therapy or these cells can activate cancer stem cell. SCUBE2 is a novel secreted and membrane-anchored protein which has been reported to its role in better prognosis and inhibition of cancer cell proliferation. Our study aims to observe whether stem cell can up-regulate SCUBE2 gene in MCF7 breast cancer cell line. We used in vitro study using MCF-7 cell treated with stem cell derived from placenta Wharton's jelly which has been known for its stemness and widely used. Our results showed that MCF-7 cell line grows up rapidly in 6-well culture dish. Stem cell was cultured in 6-well dish. After 50%-60% MCF-7 confluence, we co-cultured these cells with stem cells for 24 hours and 48 hours. We hypothesize SCUBE2 gene which is previously known for its higher expression in better prognosis of breast cancer, is up-regulated after stem cells addition in MCF7 culture dishes.

Keywords: breast cancer cells, inhibition of cancer cells, mesenchymal stem cells, SCUBE2

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Authors: Dayane de Almeida

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This work aims at presenting a study that demonstrates the usability of categories of analysis from Discourse Semiotics – also known as Greimassian Semiotics in authorship cases in forensic contexts. It is necessary to know if the categories examined in semiotic analysis (the ‘grammar’ of the content plane) can distinguish authors. Thus, a study with 4 sets of texts from a corpus of ‘not on demand’ written samples (those texts differ in formality degree, purpose, addressees, themes, etc.) was performed. Each author contributed with 20 texts, separated into 2 groups of 10 (Author1A, Author1B, and so on). The hypothesis was that texts from a single author were semiotically more similar to each other than texts from different authors. The assumptions and issues that led to this idea are as follows: -The features analyzed in authorship studies mostly relate to the expression plane: they are manifested on the ‘surface’ of texts. If language is both expression and content, content would also have to be considered for more accurate results. Style is present in both planes. -Semiotics postulates the content plane is structured in a ‘grammar’ that underlies expression, and that presents different levels of abstraction. This ‘grammar’ would be a style marker. -Sociolinguistics demonstrates intra-speaker variation: an individual employs different linguistic uses in different situations. Then, how to determine if someone is the author of several texts, distinct in nature (as it is the case in most forensic sets), when it is known intra-speaker variation is dependent on so many factors?-The idea is that the more abstract the level in the content plane, the lower the intra-speaker variation, because there will be a greater chance for the author to choose the same thing. If two authors recurrently chose the same options, differently from one another, it means each one’s option has discriminatory power. -Size is another issue for various attribution methods. Since most texts in real forensic settings are short, methods relying only on the expression plane tend to fail. The analysis of the content plane as proposed by greimassian semiotics would be less size-dependable. -The semiotic analysis was performed using the software Corpus Tool, generating tags to allow the counting of data. Then, similarities and differences were quantitatively measured, through the application of the Jaccard coefficient (a statistical measure that compares the similarities and differences between samples). The results showed the hypothesis was confirmed and, hence, the grammatical categories of the content plane may successfully be used in questioned authorship scenarios.

Keywords: authorship attribution, content plane, forensic linguistics, greimassian semiotics, intraspeaker variation, style

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Authors: Huamin Xu, Wenting Jia, Hong Jiang, Junxia Xie

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Rosmarinic acid (RA) is a natural acid that is found in a variety of herbs, such as rosemary and has multiple biological activities such as antioxidative, anti-inflammatory and antiviral activities. In this study, we investigated the neuroprotective effects of RA on dopaminergic system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mouse model of Parkinson’s disease (PD). The mice received oral administration of RA before MPTP injection. Results showed that the tyrosine hydroxylase expression in SN reduced and the levels of dopamine and its metabolites in the striatum decreased in MPTP intoxicated PD mice. Pretreatment with RA significantly inhibited these changes. Further studies demonstrated that MPTP treatment increased the iron content, which was counteracted by pre-treatment with RA. In addition, RA could restore the decrease of superoxide dismutase (SOD) induced by MPTP. This study provides evidence that RA could suppress MPTP-induced degeneration of the nigrostriatal dopaminergic system by regulating iron content and the expression of SOD. Thus, RA might be clinically evaluated for the prevention of neurodegenerative diseases.

Keywords: rosmarinic acid, Parkinson's disease, MPTP, dopaminergic system

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Authors: Jai Myung Yang, Na Young Kim, Sung Ho Shin

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The adverse reactions of current live smallpox vaccines and potential use of smallpox as a bioterror weapon have heightened the development of new effective vaccine for this infectious disease. In the present study, DNA vaccine vector was produced which was optimized for expression of the vaccinia virus L1 antigen in the mouse model. A plasmid IgM-tL1R, which contains codon-optimized L1R gene, was constructed and fused with an IgM signal sequence under the regulation of a SV40 enhancer. The expression and secretion of recombinant L1 protein was confirmed in vitro 293 T cell. Mice were administered the DNA vaccine by electroporation and challenged with vaccinia virus. We observed that immunization with IgM-tL1R induced potent neutralizing antibody responses and provided complete protection against lethal vaccinia virus challenge. Isotyping studies reveal that immunoglobulin G2 (IgG2) antibody predominated after the immunization, indicative of a T helper type 1 response. Our results suggest that an optimized DNA vaccine, IgM-tL1R, can be effective in stimulating anti-vaccinia virus immune response and provide protection against lethal orthopoxvirus challenge.

Keywords: DNA vaccine, electroporation, L1R, vaccinia virus

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Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

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Hsa-miRNA-139-5p (miR-139-5p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-139-5p on lung cancer is still ambiguous. In this study, we investigated the role of miR-139-5p on development of lung cancer. Results indicated miR-139-5p was significantly down-regulated in primary tumor tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-139-5p in NSCLC cell lines significantly suppressed cell growth through inhibition of cyclin D1 and up-regulation of p57(Kip2). In addition, miR-139-5p induced apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-139-5p inhibited cellular metastasis through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene c-Met was revealed to be a putative target of miR-139-5p, which was inversely correlated with miR-139-5p expression. Taken together, our results demonstrated that miR-139-5p plays a pivotal role in lung cancer through inhibiting cell proliferation, metastasis, and promoting apoptosis by targeting oncogenic c-Met.

Keywords: hsa-miRNA-139-5p (miR-139-5p), c-Met, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Ajay Kumar, Satwinderjeet Kaur

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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

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Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

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Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

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Authors: Salieg L. Munestri

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War on Terror became a principal war after the 9/11 attacks on U.S. homeland. Instead of helping to build up worldwide efforts to condemn terror and suicide bombings, the U.S.-led war on terror has given opportunities for the vast spread of terror. In much of Muslim world recently, the Bush’s Doctrine pushing all nations to choose sides in a war that is not truly a war has resulted worse effects. In the world’s most populous Muslim nation, Indonesia, more terror occurred since then. Instead of reinforcing the well-trained anti-terror military forces, Indonesian government established US-funded Special Detachment 88 to guarantee the accomplishment of war on terror in Indonesia and significantly to bring impact on regional security atmosphere. Indonesia is a potential power in Asia but it lacked off sophisticated military equipments. Consequently, Indonesia agrees to become a U.S. mutual partner in combating terrorism managed by Defense Security Cooperation Agency. The formation of elite anti-terror forces and U.S. partnerships perform Indonesia’s commitment to take a position beside the U.S. in coping with terrorism issue. However, this undeniably brings consequences on Indonesian political athmosphere, which encourages the writer to dig deep the consequences on the domestic environment of Indonesian political system. The establishment of the elite forces has aroused fluctuations within government, chiefly Indonesian House, concerning the establishment urgency, the large amount of funding, and the unpleasant performances, particularly the treatment toward suspected terrorists. Hence, evaluation process upon the Detachment 88 is highly demanding.

Keywords: anti-terror forces, Indonesia, political system, war on terror

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Authors: Wenjiang Deng, Tian Mou, Yudi Pawitan, Trung Nghia Vu

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Estimation of isoform-level gene expression from RNA-seq data depends on simplifying assumptions, such as uniform reads distribution, that are easily violated in real data. Such violations typically lead to biased estimates. Most existing methods provide a bias correction step(s), which is based on biological considerations, such as GC content–and applied in single samples separately. The main problem is that not all biases are known. For example, new technologies such as single-cell RNA-seq (scRNA-seq) may introduce new sources of bias not seen in bulk-cell data. This study introduces a method called XAEM based on a more flexible and robust statistical model. Existing methods are essentially based on a linear model Xβ, where the design matrix X is known and derived based on the simplifying assumptions. In contrast, XAEM considers Xβ as a bilinear model with both X and β unknown. Joint estimation of X and β is made possible by simultaneous analysis of multi-sample RNA-seq data. Compared to existing methods, XAEM automatically performs empirical correction of potentially unknown biases. XAEM implements an alternating expectation-maximization (AEM) algorithm, alternating between estimation of X and β. For speed XAEM utilizes quasi-mapping for read alignment, thus leading to a fast algorithm. Overall XAEM performs favorably compared to other recent advanced methods. For simulated datasets, XAEM obtains higher accuracy for multiple-isoform genes, particularly for paralogs. In a differential-expression analysis of a real scRNA-seq dataset, XAEM achieves substantially greater rediscovery rates in an independent validation set.

Keywords: alternating EM algorithm, bias correction, bilinear model, gene expression, RNA-seq

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Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

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Authors: Elham Shakerian, Reza Afarin

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The hepatic disease causes approximately 2 million deaths/year worldwide. Liver fibrosis is the last stage of numerous chronic liver diseases, and until now there is no definite cure or drug for it. Activation of hepatic stellate cells (HSCs) is the main reason for fibrosis. Transforming growth factor (TGF-β), as a main profibrogenic cytokine, if increased in these cells, leads to liver fibrosis through smad3 signaling pathways and increasing the expressions of Collagen type I and III, and actin-alpha smooth muscle (αSMA) genes. Curcumin (CUR) is a polyphenolic compound and an active ingredient derived from the rhizome of the turmeric plant that exerts effective antioxidant, anti-inflammatory, and antimicrobial activity. It has been shown that daily consumption of curcumin may have a protective effect on the liver against oxidative stress associated with alcohol consumption. In this study, we investigate the role of Curcumin in decreasing HSC activation and treating liver fibrosis. First, the human HSCs were treated with 2 ng/ml of (TGF-β) for 24 hours to become activated, then with Silibinin for 24 hours. Total RNAs were extracted, reversely transcribed into cDNA, Quantitative Real-time PCR, and western blot were performed. The mRNA expression levels of Collagen type I and III, αSMA genes, and the level of smad3 phosphorylation in TGF-β activated human HSCs treated with Curcumin were significantly reduced compared to human HSCs untreated with Curcumin. Curcumin is effective in reducing the expression of fibrogenic genes in the activated human HSCs treated with TGFB through downregulation of the TGF-β/smad3 signaling pathway. Therefore, Curcumin possesses significant antifibrotic properties in hepatic fibrosis

Keywords: hepatic fibrosis, human HSCs, curcumin, fibrogenic genes

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Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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Authors: Pureun-Haneul Lee, Byeong-Gon Kim, Sun-Hye Lee, An-Soo Jang

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Background: Nanoparticles may pose adverse health effects due to particulate matter inhalation. Nanoparticle exposure induces cell and tissue damage, causing local and systemic inflammatory responses. The inflammasome is a major regulator of inflammation through its activation of pro-caspase-1, which cleaves pro-interleukin-1β (IL-1β) into its mature form and may signal acute and chronic immune responses to nanoparticles. Objective: The aim of the study was to identify whether nanoparticles exaggerates inflammasome pathway leading to airway inflammation and hyperresponsiveness in an allergic mice model of asthma. Methods: Mice were treated with saline (sham), OVA-sensitized and challenged (OVA), or titanium dioxide nanoparticles. Lung interleukin 1 beta (IL-1β), interleukin 18 (IL-18), NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and caspase-1 levels were assessed with Western Blot. Caspase-1 was checked by immunohistochemical staining. Reactive oxygen species were measured for the marker 8-isoprostane and carbonyl by ELISA. Results: Airway inflammation and hyperresponsiveness increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. TiO2 nanoparticles treatment increased IL-1β and IL-18 protein expression in OVA-sensitized/challenged mice. TiO2 nanoparticles augmented the expression of NLRP3 and caspase-1 leading to the formation of an active caspase-1 in the lung. Lung caspase-1 expression was increased in OVA-sensitized/challenged mice and these responses were exaggerated by TiO2 nanoparticles exposure. Reactive oxygen species was increased in OVA-sensitized/challenged mice and in OVA-sensitized/challenged plus TiO2 exposed mice. Conclusion: Our data demonstrate that inflammasome pathway activates in asthmatic lungs following nanoparticles exposure, suggesting that targeting the inflammasome may help control nanoparticles-induced airway inflammation and responsiveness.

Keywords: bronchial asthma, inflammation, inflammasome, nanoparticles

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Authors: Ebrahim Rahmani, Siyamak Moazeni

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According to the Iraq's first constitutional law (approved 2005), Iraq is an independent with sovereignty and its governmental structure is parliamentary democratic republic and federal. Even in reforms in 2009, this article of law did not changed at all. But considering the existence of this emphasis and clarity which is mentioned in the law, different and sometimes contradictory interpretations and positions are expressed about federalism in the way that we can say, considering the importance of the matter, federalism is a focus point to create and expansion of the cold war among leaders of different groups of the country. Iraq's today political and security position has granted the suitable opportunity to Iraq's Kurdistan in appearing of the recent security crisis to increase its share from the central political power or to achieve to its independent dream. The federalism the weakest point of Iraq's territorial integrity in a way that if different groups do not come to a consensus about it and do not think about a mechanism which is accepted by all of them, this can effect on and Iraq's political stability and security. Iraq's Kurdistan follows the option of disintegration and separation under the shadow of political and security changes, even with existence of some Iraqi groups' hopes regarding the improvement of situation after parliament election and also considering Masoud Barezani's power will for separation from Iraq as well as regarding special international changes and disintegration of Karime from Ukraine and ISIS crises; concerns have been created among regional and international powers and interior players. In this article, a paradox due constitutional law about federalism, Iraq's central government view and its politicians to the matter and the regional effect of this action on region's geopolitics are reviewed as well.

Keywords: constitutional law, federalism, decomposition, Iraq's Kurdistan

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Authors: Muhammet Erbay

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The phenomenon of communication that has been studied by different disciplines has social, political and economical aspects. The scope of communication has extended from a traditional content to the modern world which is under the control of mass media. Nowadays, thanks to globalization and technological facilities, many companies, public or international institutions take advantage of new communication technologies and overhaul their policies. European Union (EU) is one of the effective institutions in this sphere. It aims to harmonize the communication infrastructure and policies of member countries which have gone through the process of political unification. It is a significant problem for the unification of EU to have legal restrictions or critical differences in communication facilities among countries while technology stands at the center of economic and social life. Therefore, EU institutions place a particular importance to their communication policies. Besides, communication processes have a vital importance in creating a European public opinion in the process of political integration. Based on the evaluation above, the aim of this paper is to analyze the cohesion process of Turkey that tries to take an active role in EU communication policies and has on-going negotiations. This article does not only confine itself to the technical details of communication policies but also aims to evaluate socio-political dimension of the process. Therefore, a corporate review has been featured in the study and Turkey's compliance process in communication policies on European Union has been evaluated by the means of deduction method. Some problematic areas have been identified in compliance process on communication policies such as human rights and minority rights, whereas compliance process on communication infrastructure and technology proceeds effectively.

Keywords: communication policies, European Union, integration, Turkey

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Authors: Mohammad Jamiu Abdullahi, Shykh Ahmed Abdussalam

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The emergence of Arabic on the shore of West Africa heralded the practise of Islam and advocation for a just and egalitarian society. Islam, it was argued, has been perverted and subverted by the Hausa leadership. This necessitated the call for reforming Islam. Al-Shaykh Usman Bin Fodio grabbed the opportunity and fought the perverts to restore the glory of Islam and establish shari'ah way of life. This was the practice, especially in the northern part of Nigeria until the incursion of colonialism. The conquest of the colonial master halted the rule of jihadi leaderships and subjected them to colonialism under which only some aspects of Islamic system considered potentially beneficial to the British interest were retained. The current socio-political and economic crises in Nigeria has necessitated the need to look inwardly to the bulk of works, in Arabic, left behind by the Muslim scholars to help to salvage the country from its present political crisis, economic paralysis and legal decadence. This paper, therefore, examines the relevance of Arabic literary works that housed political/legal theories to salvaging the country from its present political crises, economic paralysis and legal decadence.

Keywords: Arabic Fodio Nigeria security, advocacy governance scholar Usman, British colonial perspective shaykh, leadership Islam jihad politics

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Authors: Israel Oguche

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Journalism practice has faced several challenges across the globe, particularly in developing countries such as Nigeria. While Nigeria has thrived under democratic experiment for twenty years since the return to democracy in 1999, there is still a great lacuna in freedom of expression, such that the presidents, though elected democratically, have had the tendencies to use military might in clamping down on journalism practices across the country. Under Muhammadu Buhari, it seems Nigeria has returned to the military era when powers were used against who says what, on a media, so today, in Nigeria, there are obvious cases of outright human rights violations and detention of journalists whose offenses were not spelled out. From Abiri Jones to Abba Jalingo and Omoyele Sowore, Nigeria journalists have been placed under the cocoon of the tyrannical administration of Muhammadu Buhari, the president, with subsequent clamping down on the instruments of freedoms such as access to justice and fair hearing. This paper gave vivid analytical and empirical perspectives of journalism practice under the dark days of Muhammadu Buhari as Nigeria’s president. The objectives include; examining the core cases of attacks on journalists since 2015 to date, determining the burden of practicing journalism in a tyrannical government, reeling out the effects of restrictive practices of journalism on freedom of expression among Nigerians and proffering solutions for improvement in the years ahead. Using the cognitive dissonance theory, the survey method was used for the study, with qualitative research analysis as a tool for data presentation. In the findings, the number of journalists in jail for publishing objectively under the Buhari administration remains high while the government has clamped down on freedom of expression among the people. The study concluded that there is a need for repelling of laws made by the Nigeria government in order to save the Nigerian journalism industry from total collapse.

Keywords: communication, developing democracy, press freedom, journalism practices

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Authors: Redvan Ghasemlounia, Elham Ansari, Hikmet Kerem Cigizoglu

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Hydrological modeling in arid and semi-arid regions is very important. Iran has many regions with these climate conditions such as Chaharmahal and Bakhtiari province that needs lots of attention with an appropriate management. Forecasting of hydrological parameters and estimation of hydrological events of catchments, provide important information that used for design, management and operation of water resources such as river systems, and dams, widely. Discharge in rivers is one of these parameters. This study presents the application and comparison of some estimation methods such as Feed-Forward Back Propagation Neural Network (FFBPNN), Multi Linear Regression (MLR), Gene Expression Programming (GEP) and Bayesian Network (BN) to predict the daily flow discharge of the Soolegan River, located at Chaharmahal and Bakhtiari province, in Iran. In this study, Soolegan, station was considered. This Station is located in Soolegan River at 51° 14՜ Latitude 31° 38՜ longitude at North Karoon basin. The Soolegan station is 2086 meters higher than sea level. The data used in this study are daily discharge and daily precipitation of Soolegan station. Feed Forward Back Propagation Neural Network(FFBPNN), Multi Linear Regression (MLR), Gene Expression Programming (GEP) and Bayesian Network (BN) models were developed using the same input parameters for Soolegan's daily discharge estimation. The results of estimation models were compared with observed discharge values to evaluate performance of the developed models. Results of all methods were compared and shown in tables and charts.

Keywords: ANN, multi linear regression, Bayesian network, forecasting, discharge, gene expression programming

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Authors: Benoît Leclercq, Ilse Depraetere

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The goal of this presentation is to shed new light on the semantics and pragmatics of be able to. It presents the results of a corpus analysis based on data from the BNC (British National Corpus), and discusses these results in light of a specific stance on the semantics-pragmatics interface taking into account recent developments. Be able to is often discussed in relation to can and could, all of which can be used to express ability. Such an onomasiological approach often results in the identification of usage constraints for each expression. In the case of be able to, it is the formal properties of the modal expression (unlike can and could, be able to has non-finite forms) that are in the foreground, and the modal expression is described as the verb that conveys future ability. Be able to is also argued to expressed actualised ability in the past (I was able/could to open the door). This presentation aims to provide a more accurate pragmatic-semantic profile of be able to, based on extensive data analysis and one that is embedded in a very explicit view on the semantics-pragmatics interface. A random sample of 3000 examples (1000 for each modal verb) extracted from the BNC was analysed to account for the following issues. First, the challenge is to identify the exact semantic range of be able to. The results show that, contrary to general assumption, be able to does not only express ability but it shares most of the root meanings usually associated with the possibility modals can and could. The data reveal that what is called opportunity is, in fact, the most frequent meaning of be able to. Second, attention will be given to the notion of actualisation. It is commonly argued that be able to is the preferred form when the residue actualises: (1) The only reason he was able to do that was because of the restriction (BNC, spoken) (2) It is only through my imaginative shuffling of the aces that we are able to stay ahead of the pack. (BNC, written) Although this notion has been studied in detail within formal semantic approaches, empirical data is crucially lacking and it is unclear whether actualisation constitutes a conventional (and distinguishing) property of be able to. The empirical analysis provides solid evidence that actualisation is indeed a conventional feature of the modal. Furthermore, the dataset reveals that be able to expresses actualised 'opportunities' and not actualised 'abilities'. In the final part of this paper, attention will be given to the theoretical implications of the empirical findings, and in particular to the following paradox: how can the same expression encode both modal meaning (non-factual) and actualisation (factual)? It will be argued that this largely depends on one's conception of the semantics-pragmatics interface, and that this need not be an issue when actualisation (unlike modality) is analysed as a generalised conversational implicature and thus is considered part of the conventional pragmatic layer of be able to.

Keywords: Actualisation, Modality, Pragmatics, Semantics

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Authors: Shayli Varasteh Moradi, Wayne A. Johnston, Dejan Gagoski, Kirill Alexandrov

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The demand for a rapid and more efficient technique to identify protein-protein interaction particularly in the areas of therapeutics and diagnostics development is growing. The method described here is a rapid in vitro protein-protein interaction analysis approach based on AlphaLISA technology combined with Leishmania tarentolae cell-free protein production (LTE) system. Cell-free protein synthesis allows the rapid production of recombinant proteins in a multiplexed format. Among available in vitro expression systems, LTE offers several advantages over other eukaryotic cell-free systems. It is based on a fast growing fermentable organism that is inexpensive in cultivation and lysate production. High integrity of proteins produced in this system and the ability to co-express multiple proteins makes it a desirable method for screening protein interactions. Following the translation of protein pairs in LTE system, the physical interaction between proteins of interests is analysed by AlphaLISA assay. The assay is performed using unpurified in vitro translation reaction and therefore can be readily multiplexed. This approach can be used in various research applications such as epitope mapping, antigen-antibody analysis and protein interaction network mapping. The intra-viral protein interaction network of Zika virus was studied using the developed technique. The viral proteins were co-expressed pair-wise in LTE and all possible interactions among viral proteins were tested using AlphaLISA. The assay resulted to the identification of 54 intra-viral protein-protein interactions from which 19 binary interactions were found to be novel. The presented technique provides a powerful tool for rapid analysis of protein-protein interaction with high sensitivity and throughput.

Keywords: AlphaLISA technology, cell-free protein expression, epitope mapping, Leishmania tarentolae, protein-protein interaction

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Authors: Manali Jain, Neeta Singh, Raunaq Fatima, Soniya Nityanand, Mandakini Pradhan, Chandra Prakash Chaturvedi

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Isolated Congenital Heart Defect (ICHD) is the major cause of neonatal death worldwide among all forms of CHDs. A significant proportion of fetuses with ICHD die in the neonatal period if no treatment is provided. Recently, stem cell therapies have emerged as a potential approach to ameliorate ICHD in children. ICHD is characterized by cardiac structural abnormalities during embryogenesis due to alterations in the cardiomyogenic properties of a pool of cardiac progenitors/ stem cells associated with fetal heart development. The stem cells present in the amniotic fluid (AF) are of fetal origin and may reflect the physiological and pathological changes in the fetus during embryogenesis. Therefore, in the present study, the cardiomyogenic potential of AF-MSCs derived from fetuses with ICHD (ICHD AF-MSCs) has been evaluated and compared with that of AF-MSCs of structurally normal fetuses (normal AF-MSCs). Normal and ICHD AF-MSC were analyzed for the expression of cardiac progenitor markers viz., stage-specific embryonic antigen-1 (SSEA-1), vascular endothelial growth factor 2 (VEGFR-2) and platelet-derived growth factor receptor-alpha (PDGFR-α) by flow cytometry. The immunophenotypic characterization revealed that ICHD AF-MSCs have significantly lower expression of cardiac progenitor markers VEGFR-2 (0.14% ± 0.6 vs.48.80% ± 0.9; p <0.01), SSEA-1 (70.86% ± 2.4 vs. 88.36% ±2.7; p <0.01), and PDGFR-α (3.92% ± 1.8 vs. 47.59% ± 3.09; p <0.01) in comparison to normal AF-MSCs. Upon induction with 5’-azacytidine for 21 days, ICHD AF-MSCs showed a significantly down-regulated expression of cardiac transcription factors such as GATA-4 (0.4 ± 0.1 vs. 6.8 ± 1.2; p<0.01), ISL-1 (2.3± 0.6 vs. 14.3 ± 1.12; p<0.01), NK-x 2-5 (1.1 ± 0.3 vs. 14.1 ±2.8; p<0.01), TBX-5 (0.4 ± 0.07 vs. 4.4 ± 0.3; p<0.001), and TBX-18 (1.3 ± 0.2 vs. 4.19 ± 0.3; p<0.01) when compared with the normal AF-MSCs. Furthermore, immunocytochemical staining revealed that both types of AF-MSCs could differentiate into cardiovascular lineages and express cardiomyogenic, endothelial, and smooth muscle actin markers, viz., cardiac troponin (cTNT), CD31, and alpha-smooth muscle actin (α-SMA). However, normal AF-MSCs showed an enhanced expression of cTNT (p<0.001), CD31 (p<0.01), and α-SMA (p<0.05), compared to ICHD AF-MSCs. Overall, these results suggest that the ICHD-AF-MSCs have a defective cardiomyogenic differentiation potential and that the defects in these stem cells may have a role in the pathogenesis of ICHD.

Keywords: amniotic fluid, cardiomyogenic potential, isolated congenital heart defect, mesenchymal stem cells

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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