Search results for: political expression
3364 Role of Judiciary in Developing Countries
Authors: Amir Shafiq, Asif Shahzad, Shabbar Mehmood, Muhammad Saeed, Hamid Mustafa
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Administration of justice in a society is evolutionary process. In pre-modern societies vital organs that we consider separate today i.e. legislation, implementation and adjudication were controlled by a King, the sovereign authority. Whereas now it is recognized that Development of a country revolves in seven arenas i.e. Civil Society, Political Society, Economic Society, Legislature, Judiciary, Executive & Bureaucracy. Each society whether developing or developed, has need of institutions and structures that can resolve difference of opinions of private or public nature between contending parties. Administration of justice has a key-role in the development of the society. Through this paper, it is to highlight that an independent judiciary having the support of public opinion therefore is inevitable to wriggle out from such problems in order to restore and protect the fundamental rights, constitution and democratic political system in third world countries like Pakistan.Keywords: role of judiciary, developing countries, judicial activism, present scenario
Procedia PDF Downloads 3923363 On the Relationship between the Concepts of "[New] Social Democracy" and "Democratic Socialism"
Authors: Gintaras Mitrulevičius
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This text, which is based on the conference report, seeks to briefly examine the relationship between the concepts of social democracy and democratic socialism, drawing attention to the essential aspects of its development and, in particular, discussing the contradictions in the relationship between these concepts in the modern period. In the preparation of this text, such research methods as historical, historical-comparative methods were used, as well as methods of analyzing, synthesizing, and generalizing texts. The history of the use of terms in social democracy and democratic socialism shows that these terms were used alternately and almost synonymously. At the end of the 20th century, traditional social democracy was transformed into the so-called "new social democracy." Many of the new social democrats do not consider themselves democratic socialists and avoid the historically characteristic identification of social democracy with democratic socialism. It has become quite popular to believe that social democracy is a separate ideology from democratic socialism. Or that it has become a variant of the ideology of liberalism. This is a testimony to the crisis of ideological self-awareness of social democracy. Since the beginning of the 21st century, social democracy has also experienced a growing crisis of electoral support. This, among other things, led to her slight shift to the left. In this context, some social democrats are once again talking about democratic socialism. The rise of the ideas of democratic socialism in the United States was catalyzed by Bernie Sanders. But the proponents of democratic socialism in the United States have different concepts of democratic socialism. In modern Europe, democratic socialism is also spoken of by leftists of non-social democratic origin, whose understanding is different from that of democratic socialism inherent in classical social democracy. Some political scientists also single out the concepts in question. Analysis of the problem shows that there are currently several concepts of democratic socialism on the spectrum of the political left, both social-democratic and non-social-democratic.Keywords: democratic socializm, socializm, social democracy, new social democracy, political ideologies
Procedia PDF Downloads 1113362 Immigration without Settlement: Causes and Consequences of Exclusionary Migration Regime in East Asia
Authors: Yen-Fen Tseng
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Studying migration regimes enables one to identify clusters of countries with policy features in common. A few researchers have pointed out the origin of hardship experienced by foreign workers in Taiwan, Japan, and South Korea, stems from their exclusionary migration regime. This paper aims to understand the causes and consequences of the East Asia migration regime, exploring the common exclusionary policies features of Taiwan, Japan, and South Korea, focusing on the foreign labor policy. It will then present explanations as to factors shaping migration regime; the perspective of factors within political system is adopted, as opposed to political economy and pluralist society approach. In the minds of political elites across East Asia, there exists a powerful belief in mono-ethnicity, namely, the benefits of mono-ethnicity and the social ill of “minority problems”. Guest workers policies of various alterations become the compromise between the want for foreign labor and the desire to maintain mono-ethnicity. The paper discusses the absence of immigrant settlement and formation of ethnic communities as a result of the reluctant hosts. Migrant workers in these societies commonly suffer from irregular working conditions as well as unprotected rights out of their denied legality. The case of Taiwan will be presented with greater details, drawing on data from both first-hand and secondary sources.Keywords: migration regime, guest worker policies, East Asia, society
Procedia PDF Downloads 3793361 Women’s Sport on the Brazilian Governmental Agenda
Authors: Giovanna X. De Moura, Fernando A. Starepravo
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In recent years, the discussion of women in sports has been part of the political agenda in several countries. However, in the Brazilian scope, it is possible to say that women's sport has not become a social problem recognized by political actors and, therefore, it has not entered the country's governmental agenda. Thus, this work aimed to analyze why sport for women is not on the Brazilian government's agenda. For this, it was interviewed six women considered to be stakeholders in sports, that is, women who influence or are influenced by sports. The interviews were based on a semi-structured script and carried out in the year 2022. Due to the difficulties of commuting and of the schedule of the interviewees, some interviews were carried out in person, others by video call or telephone and others by WhatsApp. The interviews were transcribed and analyzed using Bardin's Content Analysis. As a result, from the stakeholders' perception, it was ascertained that women's sport is not considered a political problem because both sport and politics are considered masculinized fields, making it difficult for women to be present in both spaces. Besides, not only the sport of women but sport in general, is seen as just a marketing tool and a way of getting financial return for companies, being neglected in government plans. Due to this fact, private institutions, corporative means, federations and confederations have been mobilized in the creation of policies that seek changes in the current scenario. Despite this, two PLs (PL 6263/2019 and PL 5297/2020) have been in the process since 2019 but have not been approved yet due to the failure to submit amendments within the established deadline. In order to change this reality, the ones surveyed suggested that there should be not only different types of women represented on the most varied fronts of sports but also more visibility of the issue of women in this field. Furthermore, they mentioned the importance of the creation of specific plans and policies that guarantee a safe place for women and that are consolidated as State policies. In addition, the need for more women in political decision-making positions was also mentioned. It was concluded that women's sport appears on the agenda at a secondary level since it is included on the legislative, and political agenda but not in the executive branch. In addition, there is not enough movement and mobilization in favor of women's sports for it to become a discussion in the field of politics. Regarding the Multiple Streams Model, women's sport is present only in the ideas stream, as there are solutions and ideas for improvements in this field. Finally, it was pointed that there is still a strong dependence on the State for the creation of policies that seek improvements in the participation of girls and women in sport, hence, being necessary the creation of multicentric policies, including non-governmental agents in the process of elaborating policies.Keywords: agenda, politics, stakeholders, women’s sport
Procedia PDF Downloads 833360 Turkey in Minds: Cognitive and Social Representation of "East" and "West"
Authors: Feyzan Tuzkaya, Nihan S. Soylu, Caglar Solak, Mehmet Peker, Hilal Peker, Kemal Ozeralp, Ceren Mete, Ezgi Mehmetoglu, Mehmet Karasu, Cihan Elci, Ece Akca, Melek Goregenli
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Perception, evaluation and representation of the environment have been the subject of many disciplines including psychology, geography and architecture. In environmental and social psychology literature there are several evidences which suggest that cognitive representations about a place consisted of not only geographic items but also social and cultural. Mental representations of residence area or a country is influenced and determined by social-demographics, the physical and social context. Thus, all mental representations of a given place are also social representations. Cognitive maps are the main and common instruments that are used to identify spatial images and the difference between physical and subjective environments. The aim of the current study is investigating the mental and social representations of Turkey in university students’ minds. Data was collected from 249 university students from different departments (i.e. psychology, geography, history, tourism departments) of Ege University. Participants were requested to reflect Turkey in their mind onto the paper drawing sketch maps. According to the results, cognitive maps showed geographic aspects of Turkey as well as the context of symbolic, cultural and political reality of Turkey. That is to say, these maps had many symbolic and verbal items related to critics on social and cultural problems, ongoing ethnic and political conflicts, and actual political agenda of Turkey. Additionally, one of main differentiations in these representations appeared in terms of the East and West side of the Turkey, and the representations of the East and West was varied correspondingly participants’ cultural background, their ethnic values, and where they have born. The results of the study were discussed in environmental and social psychological perspective considering cultural and social values of Turkey and current political circumstances of the country.Keywords: cognitive maps, East, West, politics, social representations, Turkey
Procedia PDF Downloads 4083359 Nitric Oxide and Blood Based Ratios as Promising Immuno-Markers in Patients with Complicated Crohn’s Disease: Benefits for Predicting Therapy Response
Authors: Imene Soufli, Abdelkrim Hablal, Manel Amri, Moussa Labsi, Rania Sihem Boussa, Nassim Sid Idris, Chafia Touil-Boukoffa
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Crohn’s Disease (CD) is a relapsing–remitting inflammatory bowel disease with a progressive course. The aim of our study was to evaluate the relationship between the immunomarkers: Nitric Oxide (NO), pro-inflammatory cytokines, and blood count-based ratios and the outcome of corticosteroid or anti-TNF-α therapy in patients with complicated Crohn’s Disease. In this context, we evaluated the NLR as the ratio of neutrophil count to lymphocyte count, PLR as the ratio of platelet counts to lymphocyte count, and MLR as the ratio of monocyte count to lymphocyte count in patients and controls. Furthermore, we assessed NO production by the Griess method in plasma along with iNOS and NF-κB expression by immunofluorescence method in intestinal tissues of patients and controls. In the same way, we evaluated plasma TNF-α, IL-17A, and IL-10 levels using ELISA. Our results indicate that blood count-based ratios NLR, PLR, and MLR were significantly higher in patients compared to controls. In addition, increased systemic levels of NO, TNF-α, and IL-17A and colonic expression of iNOS and NF-κB were observed in the same patients. Interestingly, the high ratio of NLR and MLR, as well as NO production, was significantly decreased in treated patients. Collectively, our findings suggest that Nitric Oxide, as well as the blood count-based ratios (NLR, PLR, MLR), could constitute useful immuno-markers in complicated Crohn’s Disease, predicting the response to treatmentKeywords: complicated crohn’s disease, nitric oxide, blood count-based ratios, treatments, pro-inflammatory cytokines
Procedia PDF Downloads 773358 Investigation of Ezetimibe Administration on Cell Survival Markers in Kidney Ischemia
Authors: Zahra Heydari
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Introduction: One of the major clinical issues is acute renal failure, which is caused by ischemia-reperfusion of the kidney and is associated with high mortality. Despite advances in this area, important issues such as tissue necrosis, cell apoptosis, and so on in damaged tissue are suggestive for more researches and study on this subject. Objective: Evaluation of the potential utility of Ezetimibe in reducing injuries and cell death induced by kidney ischemia/ reperfusion through inducing expression changes of different cellular pathways in adult Sprague-Dawley rats. Materials and methods: Forty rats weighing 180-200g were divided into 4 groups. For this purpose, the first right kidneys of the rats were removed during surgery. After 20 days, the left renal artery was closed with a soft clamp and reperfusion was performed. After 24 hours, blood samples were collected and sent to the laboratory with kidneys to measure bax and bcl-2 by Western blotting and histopathological tests. Results: Quantitative damage reviews of Kidney tissue indicates damage Acute and severe tubular lesions were observed in the ischemia group. Also, the amount of injury was significantly reduced in the treatment group. There was also a significant difference between the ischemia and sham groups. In general, the results show that a single dose of 1.2 mg/kg of ezetimibe can reduce the bax/ bcl-2 ratio compared to the ischemia group. In general, the results showed Ezetimibe is effective in reducing cell damage and death due to ischemia/ reperfusion after renal ischemia through changes in the expression of various cellular pathways in rats.Keywords: acute renal failure, renal ischemia-reperfusion injury, ezetimibe, apoptosis
Procedia PDF Downloads 1943357 Lactobacillus rhamnosus GG Increases the Re-Epithelialization Rate of Model Wounds by Stimulating Keratinocyte Migration in Ex-Vivo
Authors: W. Mohammedsaeed, A. J. Mcbain, S. M. Cruickshank, C. A. O’Neill
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Many studies have demonstrated the importance of probiotics and their potential therapeutic effects within the gut. Recently, the possible therapeutic effects of probiotics in other tissues have also begun to be investigated. Comparatively few studies have evaluated the use of topical probiotics in relation to the skin. In this study, we have conducted preliminary investigations into whether a well-known probiotic, Lactobacillus rhamnosus GG (LGG), can increase the rate of re-epithelialization in a model wound. Full-thickness skin was obtained from individuals undergoing elective cosmetic surgery. This skin was wounded using excisional punch and cultured using a serum-free medium, either in the presence or absence of L. rhamnosus GG lysate. Histological staining of the sections was performed with Haematoxylin& Eosin E to quantify “epithelial tongue length”. This is the length of the new epithelial ‘tongue’ that grows and covers the exposed dermis at the inner wound edges. The length of the new epithelial ‘tongue’ was compared in untreated section and section treated with and L. rhamnosus GG made using108CFU/ml bacterial cells. L. rhamnosus GG lysate enhanced significantly the re-epithelialisation of treated wounds compared with that of untreated wounds (P=0.005, n=3). Tongue length, at day 1 was 7.55μm 0.15, at day 3 it was 18.5μm 0.25 and at day 7 was 22.9μm 0.35. These results can be compared with untreated cultures in which tongue length was 3.25μm 0.35, day 3 was 9.65μm 0.25 and day 7 was 13.5μm 0.15 post-wounding. In ex-vivo proliferation and migration cells were measured by determining the expression of nuclear proliferation marker Ki-67 and the expression of Phosphorylated cortactin respectively demonstrated that L. rhamnosus GG significantly increased NHEK proliferation and migration rates relative to controls. However, the dominant mechanism was migration because in ex-vivo skin treated with the L. rhamnosus GG up-regulated the gene expression of the chemokine receptor and ligands CXCR2 and CXCL2 comparing with controls (P=0.02, P=0.03 respectively, n=3). High levels of CXCL2/CXCL2 have already been implicated in multiple aspects of stimulation of wound healing through activation of keratinocyte migration. These data demonstrate that lysates from Lactobacillus rhamnosus GG increase re-epithelialization by stimulation of keratinocyte migration. The current study identifies the partial mechanism that contribute to stimulating the wound-healing process ex vivo in response to L. rhamnosus GG lysate is an increase in the production of CXCL2/ CXCR2 in ex vivo models. The use of probiotic lysates potentially offers new options to develop treatments that could improve wound healing.Keywords: Lactobacillus rhamnosus GG, wounds, migration, lysate
Procedia PDF Downloads 3273356 Effects of Boron Compounds in Rabbits Fed High Protein and Energy Diet: A Metabolomic and Transcriptomic Approach
Authors: Nuri Başpınar, Abdullah Başoğlu, Özgür Özdemir, Çağlayan Özel, FundaTerzi, Özgür Yaman
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Current research is targeting new molecular mechanisms that underlie non-alcoholic fatty liver disease (NAFLD) and associated metabolic disorders like nonalcoholic steatohepatitis (NASH). Forty New Zealand White rabbits have been used and fed a high protein (HP) and energy diet based on grains and containing 11.76 MJ/kg. Boron added to 3 experimental groups’ drinking waters (30 mg boron/L) as boron compounds. Biochemical analysis including boron levels, and nuclear magnetic resonance (NMR) based metabolomics evaluation, and mRNA expression of peroxisome proliferator-activated receptor (PPAR) family were performed. LDL-cholesterol concentrations alone were decreased in all the experimental groups. Boron levels in serum and feces were increased. Content of acetate was in about 2x higher for anhydrous borax group, at least 3x higher for boric acid group. PPARα mRNA expression was significantly decreased in boric acid group. Anhydrous borax attenuated mRNA levels of PPARα, which was further suppressed by boric acid. Boron supplementation decreased the degenerative alterations in hepatocytes. Except borax group other boron groups did not have a pronounced change in tubular epithels of kidney. In conclusion, high protein and energy diet leads hepatocytes’ degenerative changes which can be prevented by boron supplementation. Boric acid seems to precede in this effectiveness.Keywords: high protein and energy diet, boron, metabolomics, transcriptomic
Procedia PDF Downloads 6253355 Defence Industry in the Political Economy of State and Business Relations
Authors: Hatice Idil Gorgen
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Turkey has been investing in its national defence industrial base since the 1980s. State’s role in defence industry showed differences in Turkey. Parallel with this, ruling group’s attitude toward companies in defence sector varied. These changes in policies and behaviors of the state have occurred throughout such milestones as political and economic turmoil in domestic and international level. Hence, it is argued that state’s role, relations with private companies in defense sector and its policies towards the defense industry has shown differences due to the international system, political institutions, ideas and political coalitions in Turkey since the 1980s. Therefore, in order to see changes in the role of the state in defence sector, this paper aims to indicate first, history of state’s role in production and defence industry in the post-1980s era. Secondly, to comprehend the changes in the state’s role in defence industry, Stephan Haggard’s sources of policy change will be provided in the theoretical ground. Thirdly, state cooperated, and joint venture defence firms, state’s actions toward them will be observed. The remaining part will explore the underlying reasons for the changes in the role of the state in defence industry, and it implicitly or explicitly impacts on state business relations. Major findings illustrate that targeted idea of self-sufficient or autarky Turkey to attract domestic audience and to raise the prestige through defence system; ruling elites can regard defence industry and involved business groups as a mean for their ends. State dominant value, sensitive perception which has been ever since Ottoman Empire, prioritizes business groups in defence industry compared to others and push the ruling elites to pursue hard power in defence sectors. Through the globally structural transformation in defence industry, integration of Turkey to liberal bloc deepened and widened interdependence among states. Although it is a qualitative study, it involves the numerated data and descriptive statistics. Data will be collected by searching secondary sources from the literature, examining official documents of ministry of defence, and other appropriate ministries.Keywords: defense industry, state and business relations, public private relations, arm industry
Procedia PDF Downloads 3153354 Effect of Zinc Nanoparticles on Oxidative Stress-Related Genes and Antioxidant Enzymes Activity in the Brain of Oreochromis Niloticus and Tilapia Zillii
Authors: Salina Saddick, Mohamed Afifi, Osama Abuznadah
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This study was carried out to determine the median lethal concentrations (LC50) of Zinc nanoparticles (ZnNPs) on Oreochromis niloticus and Tilapia zillii. The biochemical and molecular potential effects of ZnNPs (500 and 2000 μg L−1) on the antioxidant system in the brain tissue of O. niloticus and T. zillii were investigated. Four hundred fish were used for acute and sub-acute studies. ZnNP LC50 concentrations were investigated in O. niloticus and T. zillii. The effect of 500 and 2000 μg L−1 ZnNPs on brain antioxidants of O. niloticus and T. zillii was investigated. The result indicated that 69 h LC50 was 5.5 ± 0.6 and 5.6 ± 0.4 for O. nilotica and T. zillii, respectively. Fish exposed to 500 μg L−1 ZnNPs showed a significant increase in reduced glutathione (GSH), total glutathione (tGSH) levels, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activity and gene expression. On the contrary, malondialdehyde (MDA) levels significantly decreased. Meanwhile, fish exposed to 2000 μg L−1 ZnNPs showed a significant decrease of GSH, tGSH levels, SOD, CAT, GR, GPx and GST activity and gene expression. On the contrary, MDA levels significantly increased. It was concluded that, the 96 h LC50 of ZnNPs was 5.5 ± 0.6 and 5.6 ± 0.4 for O. nilotica and T. zillii, respectively. ZnNPs in exposure concentrations of 2000 μg/L induced a deleterious effect on the brain antioxidant system of O. nilotica and T. zillii. In contrast, ZnNPs in exposure concentrations of 500 μg L−1 produced an inductive effect on the brain antioxidant system of O. nilotica and T. zillii.Keywords: ZnNPs, LC50, antioxidants, O. nilotica
Procedia PDF Downloads 2423353 The Experience of Head Nurse: Phenomenological Research of Implementing Islamic Leadership Style in Syarif Hidayatullah Hospital
Authors: Jamaludin Tarkim, Yoga Teguh Guntara, Maftuhah
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Islamic leadership style is model of leadership style applied by the Prophet Muhammad SAW. Islamic leadership style is applied, namely Syura (deliberation), ‘Adl bil qisth (justice, with equality), and Hurriyyah al-kalam (freedom of expression) and along with the values of Islam in the Islamic leadership style. This research aims to gain an overview of the experience of Head Nurse in the implementation of Islamic leadership style. This research is a qualitative one with descriptive phenomenology design through in-depth interviews. Participants were occupied as Head Nurse at the Hospital room Syarif Hidayatullah, set directly (purposive) with the principle of suitability (appropriateness) and sufficiency (adequacy). Retrieval of data and research conducted during the month of June 2014. Data collected in the form of recording in-depth interviews and analysis with Collazi method. This research identified four themes Syura (deliberation);‘Adl bil qisth (justice, with equality); Hurriyyah al-kalam (freedom of expression) and along with the values of Islam in the Islamic leadership style. The results of this research can provide a review of the Head Room experience in the application of Islamic leadership style at Syarif Hidayatullah Hospital already skilled leadership during the process, but the application is still not maximized. Required further research on in-depth exploration of how to get more comprehensive results from room Head Nurse experience in the application of Islamic leadership style, as well as subsequent researchers can choose a wider scope and complex so get more complete data.Keywords: experience, Islamic leadership style, head nurse, nursing management
Procedia PDF Downloads 1693352 Intramuscular Heat Shock Protein 72 and Heme Oxygenase-1 mRNA are Reduced in Patients with Type 2 Diabetes Evidence That Insulin Resistance is Associated with a Disturbed Antioxidant Defense Mechanism
Authors: Ghibeche Abderrahmane
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To examine whether genes associated with cellular defense against oxidative stress are associated with insulin sensitivity, patients with type 2 diabetes (n=7) and age-matched (n=5) and young (n=9) control subjects underwent a euglycemic-hyperinsulinemic clamp for 120 min. Muscle samples were obtained before and after the clamp and analyzed for heat shock protein (HSP)72 and heme oxygenase (HO)-1 mRNA, intramuscular triglyceride content, and the maximal activities of β-hyroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase (CS). Basal expression of both HSP72 and HO-1 mRNA were lower (P < 0.05) by 33 and 55%, respectively, when comparing diabetic patients with age-matched and young control subjects, with no differences between the latter groups. Both basal HSP72 (r = 0.75, P < 0.001) and HO-1 (r = 0.50,P < 0.05) mRNA expression correlated with the glucose infusion rate during the clamp. Significant correlations were also observed between HSP72 mRNA and both β-HAD (r = 0.61, P < 0.01) and CS (r = 0.65, P < 0.01). HSP72 mRNA was induced (P < 0.05) by the clamp in all groups. Although HO-1 mRNA was unaffected by the clamp in both the young and age-matched control subjects, it was increased (P < 0.05) ∼70-fold in the diabetic patients after the clamp. These data demonstrate that genes involved in providing cellular protection against oxidative stress are defective in patients with type 2 diabetes and correlate with insulin-stimulated glucose disposal and markers of muscle oxidative capacity. The data provide new evidence that the pathogenesis of type 2 diabetes involves perturbations to the antioxidant defense mechanism within skeletal muscle.Keywords: euglycemic-hyperinsulinemic, HSP72, mRNA, diabete
Procedia PDF Downloads 4373351 Molecular Signaling Involved in the 'Benzo(a)Pyrene' Induced Germ Cell DNA Damage and Apoptosis: Possible Protection by Natural Aryl Hydrocarbon Receptor Antagonist and Anti-Tumor Agent
Authors: Kuladip Jana
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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin
Procedia PDF Downloads 2573350 Climate Change and Land Grabbing
Authors: Akachi Odoemene
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Climate change and land grabbing are tightly interconnected in ways that are both diverse and complex. They have impacted each other in significant ways too. Both phenomena are not only a political reality, but have diverse dire implications, especially for food and livelihood security of vulnerable populations in developing economies. The critical nexus and interactions of climate change and land grabbing remain one of the challenges of sustainable development in modern times. The nuanced understanding of the nexus, importance and implications of climate change and land grabbing are the primary focus of this chapter. It begins with conceptual clarifications, particularly arguing that the absence of some important principles of engagement underline and define a land grab. It also analyses and notes a good number of contemporary land deals as 'one-sided', in which wealthy entities connive with local elites to exploit and disposes rural poor populations. The paper not only examines both global and local factors that drive land grabbing and, in some cases, their connections with the incidence of climate change, but also explores their crucial links with such sector as agriculture. It is argued and exhibited in the paper why certain societies are susceptible to the incidence of climate change and land grabbing, while the overall consequences of these phenomena on the affected societies are further interrogated. The paper concludes that the lack of political will by global political leaders to effectively combat and resolve critical issues associated with both climate change and land grabbing remains a daunting challenge. It notes that these phenomena – climate change and land grabbing – if not abated, will certainly become another set of global tragic episodes to be regretted in the future.Keywords: climate change, land grabbing, global governance, developing economies
Procedia PDF Downloads 2913349 The Social Reaction to the Wadi Salib Riots (1959) as Reflected in Contemporary Israeli Press
Authors: Ada Yurman
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Social reactions to deviant groups with political goals follow two central patterns; one that associates personal characteristics with deviant behavior, and the other that claims that society is to be blamed for deviant behavior. The establishment usually tends towards the former notion and thus disclaims any responsibility for the distress of the underprivileged, while it is usually those who oppose government policies who believe that the fault lies with society. The purpose of the present research was to examine social reactions to the Wadi Salib riots that occurred in Haifa in 1959. These riots represented the first ethnic protest within Israeli society with its ideology of the ingathering of the exiles. The central question was whether this ideology contributed to the development of a different reaction when compared to reactions to similar events abroad. This question was examined by means of analyzing articles in the Israeli press of that period. The Israeli press representing the views of the establishment was at pains to point out that the rioters were criminals, their object being to obstruct the development of society. Opposition party leaders claimed that the rioters lived in poor circumstances, which constituted a direct result of government policies. An analysis of press reports on the Wadi Salib riots indicates a correspondence between the reaction to these events and similar events abroad. Nevertheless, the reaction to the Wadi Salib riots did not only express a conflict between different political camps, but also different symbolic universes. Each group exploited the events at Wadi Salib to prove that their ideology was the legitimate one.Keywords: riots, media, political deviance, symbolic universe
Procedia PDF Downloads 1663348 Towards Resource Sufficiency in Engineering Education in Sub-Saharan Africa
Authors: Iyabosola B. Oronti, Adeoluwawale A. Adewusi, Olubusola O. Nuga
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Sub-Saharan Africa has long been known to be a region rife with poverty, inadequate health facilities, food shortages, high transport and communication costs and very low pace of infrastructural and technological development. These factors combined have led to decades of resource paucity in engineering education. Engineering is core to global development and building of capacity in engineering education with available resources in sub-Saharan Africa has become imperative. This paper identifies core political issues and policy shifts contributing adversely to this present state of affairs, and also explores the offshoots of the changing global political environment as it affects engineering education in the developing nations of sub-Saharan Africa. Opportunities for instituting resource sufficiency are examined and corrective measures that can be taken to resuscitate and stabilize the educational sector in the region are also suggested.Keywords: capacity building, engineering education, resource sufficiency, sub-Saharan Africa
Procedia PDF Downloads 4343347 Anticancer Activity of Calyx of Diospyros kaki Thunb. through Downregulation of Cyclin D1 Protein Level in Human Colorectal Cancer Cells
Authors: Jin Boo Jeong
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In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer
Procedia PDF Downloads 3113346 Intellectual Property Rights on Plant Materials in Colombia: Legal Harmonization for Food Sovereignty
Authors: Medina Muñoz Lina Rocio
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The purpose of this paper is to examine the debates related to the harmonization of intellectual property rights on plant material, the corporate governance of the seed market in Colombia and the political economy of seeds defended by indigenous communities. In recent years, the commodification of seeds through genetic engineering and political intellectual property, codified as a result of the implementation of the Free Trade Agreement with the United States, has come into conflict with the traditional production of seeds carried out by small farmers and indigenous populations. Agricultural and food practices. In order to understand the ontological dimension of conflicts over seeds, it is necessary to analyze the conceptions that indigenous communities have about good, which they consider a common element of their social organization and define them as sentient beings. Therefore, through a multiple approach, in which the intellectual property policy, the ecological aspects of seed production and the political ontology of indigenous communities are interwoven, I intend to present the discussions held by the actors involved and present the strategies of small producers to protect their interests. It demonstrates that communities have begun to organize social movements to protect such interests and have questioned the philosophy of GM corporate agriculture as a pro-life movement. Finally, it is argued that the conservation of 'traditional' seeds of the communities is an effective strategy to support their struggles for territory, identity, food sovereignty and self-determination.Keywords: intellectual property rights, intellectual property, traditional knowledge, food safety
Procedia PDF Downloads 753345 Shiva's Dance: Crisis, Local Institutions, and Private Firms
Authors: João Pereira Dos Santos
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The uneven spatial distribution of start-ups and their respective survival may reflect comparative advantages resulting from the local institutional background. For the first time, we explore this idea using Data Envelopment Analysis (DEA) to assess relative efficiency of Portuguese municipalities in this specific context. We depart from the related literature where expenditure is perceived as a desirable input by choosing a measure of fiscal responsibility and infrastructural variables in the first stage. Comparing results for 2006 and 2010, we find that mean performance decreased substantially with 1) the effects of the Global Financial Crisis; 2) as municipal population increases and 3) as financial independence decreases. A second stage is then computed employing a double-bootstrap procedure to evaluate how the regional context outside the control of local authorities (e.g. demographic characteristics and political preferences) impacts on efficiency.Keywords: entrepreneurship, political economy, public finance, accountability, crisis, efficiency, Portuguese municipalities
Procedia PDF Downloads 5013344 Analyzing the Effect of Socio-Political Context on Tourism: Perceptions of Young Tourists in Greece, Portugal and Israel
Authors: Shosh Shahrabani, Sharon Teitler-Regev, Helena Desivilya Syna, Fotini Voulgaris, Evangelos Tsoukatos, Vitor Ambrosio, Sandra M. Correia Loureiro
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International crises that affect tourism, such as terror attacks, political unrest, and economic crises have become more frequent, and their influence has become broader. The influence of such extreme events depends on their salience in the tourists' awareness. Hence, it is important to understand the mechanisms underlying tourists' selection of travel destinations, especially their perceptions of crisis-related events and the impact of the sociopolitical and economic context in their countries of origin. The current study examined how the socio-political and economic context in the home countries of potential young tourists affected their selection of travel destinations. The objective was to elucidate how the salience of various crises (economic and political) in the tourists' perceptions, due to their experiences at home, color their construal of destinations affected by similar hazards and influence their travel intentions. The study focused on student tourists from Israel, Greece, and Portugal. Today about a fifth of international tourism is based on young people, especially students. These countries were chosen since Greece and Portugal are in the midst of economic crises. In addition, Greece and Portugal have experienced political instability, while Israel has security-related problems (including terrorist incidents). In 2013, a total of 648 students, responded to a questionnaire that included questions concerning attitudes and risk perceptions regarding travel to destinations with various risk hazards as well as socio-demographic details. The results indicate that over half of the Israelis intend to visit Greece or Portugal. The majority of the Portuguese intend to visit Greece, while less than a third of them intend to visit Israel. About half of the Greeks intend to visit Portugal, and most of them do not intend to visit Israel. The results indicate that greater perceived importance of economic crises mitigates the intention to travel to destinations with economic crises for tourists from origin countries that are also marked by economic crises, such as Greece and Portugal. However, for tourists from Israel, a country with a relatively stable economy, issues related to the economy barely affect their intention to travel to the other two countries. The findings also suggest that Greeks and Portuguese who are highly concerned about political unrest are unlikely to select Israel as a tourist destination. In addition, strong apprehension regarding terrorism impedes the intention to travel to destinations marked by terrorist incidents, such as Israel. The current research contributes to the existing literature by highlighting the impact of travelers' personal previous experience with crisis on their risk perceptions and in turn on their intentions to travel to countries with similar risks. Therefore, in a world where such incidents are on the rise, understanding tourists' risk perceptions and behavior and the factors influencing their destination-related decisions are crucial for countries that wish to increase the numbers of incoming tourists.Keywords: economic crises, political instability, risk perception, young tourists
Procedia PDF Downloads 4583343 Toxicological Validation during the Development of New Catalytic Systems Using Air/Liquid Interface Cell Exposure
Authors: M. Al Zallouha, Y. Landkocz, J. Brunet, R. Cousin, J. M. Halket, E. Genty, P. J. Martin, A. Verdin, D. Courcot, S. Siffert, P. Shirali, S. Billet
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Toluene is one of the most used Volatile Organic Compounds (VOCs) in the industry. Amongst VOCs, Benzene, Toluene, Ethylbenzene and Xylenes (BTEX) emitted into the atmosphere have a major and direct impact on human health. It is, therefore, necessary to minimize emissions directly at source. Catalytic oxidation is an industrial technique which provides remediation efficiency in the treatment of these organic compounds. However, during operation, the catalysts can release some compounds, called byproducts, more toxic than the original VOCs. The catalytic oxidation of a gas stream containing 1000ppm of toluene on Pd/α-Al2O3 can release a few ppm of benzene, according to the operating temperature of the catalyst. The development of new catalysts must, therefore, include chemical and toxicological validation phases. In this project, A549 human lung cells were exposed in air/liquid interface (Vitrocell®) to gas mixtures derived from the oxidation of toluene with a catalyst of Pd/α-Al2O3. Both exposure concentrations (i.e. 10 and 100% of catalytic emission) resulted in increased gene expression of Xenobiotics Metabolising Enzymes (XME) (CYP2E1 CYP2S1, CYP1A1, CYP1B1, EPHX1, and NQO1). Some of these XMEs are known to be induced by polycyclic organic compounds conventionally not searched during the development of catalysts for VOCs degradation. The increase in gene expression suggests the presence of undetected compounds whose toxicity must be assessed before the adoption of new catalyst. This enhances the relevance of toxicological validation of such systems before scaling-up and marketing.Keywords: BTEX toxicity, air/liquid interface cell exposure, Vitrocell®, catalytic oxidation
Procedia PDF Downloads 4103342 On the Impracticality of Kierkegaard's Community of Authentic Individuals
Authors: Andrew Ka Pok Tam
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Kierkegaard has been misinterpreted as an anti-social philosopher for a long time until in recent years when there are more discussions on his concept of community in Journals and Papers inspired by Karl Bayer. Community which is based upon an individual's relations to others is different from the crowd or the public where the numerical or the majority make decisions. As a result, authenticity is only possible in the community. But Kierkegaard did not explain how we can preserve the individual's authenticity by establishing a community instead of a public in the reality. Kierkegaard was against the democratic reform in 1848 Denmark because he thought all elections mean the majority wins and the authenticity of a single individual would be suppressed. However, Kierkegaard himself does not suggest an alternative political system that may preserve the authenticity of individual. This paper aims to evaluate the possibility for us to establish a Kierkegaadian community in practice so as to preserve every individual's authenticity. This paper argues that the practicality of Kierekegaadian community is limited. In order to have effective communications and relations among individuals, a Kierkegaardian community must be small and inefficient as every individual's must remain authentic in all political decision for the whole community.Keywords: authenticity, community, individual, kierkegaard
Procedia PDF Downloads 3593341 Identification of Information War in Lithuania
Authors: Vitalijus Leibenka
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After 2014 the world of Russia’s actions in annexing Crimea has seen a hybrid war that has helped Russia achieve its goals. The world and NATO nations have pointed out that hybrid action can help achieve not only military but also economic and political goals. One of the weapons of action in hybrid warfare is information warfare tools, the use of which helps to carry out actions in the context of hybrid warfare as a whole. In addition, information war tools can be used alone, over time and for long-term purposes. Although forms of information war, such as propaganda and disinformation, have been used in the past, in old conflicts and wars, new forms of information war have emerged as a result of technological development, making the dissemination of information faster and more efficient. The world understands that information is becoming a weapon, but not everyone understands that both information war and information warfare differ in their essence and full content. In addition, the damage and impact of the use of information war, which may have worse consequences than a brief military conflict, is underestimated. Lithuania is also facing various interpretations of the information war. Some believe that the information attack is an information war and the understanding of the information war is limited to a false message in the press. Others, however, deepen and explain the essence of the information war. Society has formed in such a way that not all people are able to assess the threats of information war, to separate information war from information attack. Recently, the Lithuanian government has been taking measures in the context of the information war, making decisions that allow the development of the activities of the state and state institutions in order to create defense mechanisms in the information war. However, this is happening rather slowly and incompletely. Every military conflict, related to Lithuania in one way or another, forces Lithuanian politicians to take up the theme of information warfare again. As a result, a national cyber security center is being set up, and Russian channels spreading lies are banned. However, there is no consistent development and continuous improvement of action against information threats. Although a sufficiently influential part of society (not a political part) helps to stop the spread of obscure information by creating social projects such as “Demaskuok” and “Laikykis ten su Andriumi tapinu”, it goes without saying that it will not become a key tool in the fight against information threats. Therefore, in order to achieve clean dissemination of information in Lithuania, full-fledged and substantial political decisions are necessary, the adoption of which would change the public perception of the information war, its damage, impact and actions that would allow to combat the spread. Political decisions should cover the educational, military, economic and political areas, which are one of the main and most important in the state, which would allow to fundamentally change the situation against the background of information war.Keywords: information war, information warfare, hybrid war, hybrid warfare, NATO, Lithuania, Russia
Procedia PDF Downloads 623340 Determining the Policy Space of the Partido Socialista Obrero Español Government in Managing Spain's Economic and Financial Crisis
Authors: A. Pascual Ramsay
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Accounts of the management of the economic and euro crisis in Spain have been dominated by an emphasis on external constraints. However, this approach leaves unanswered important questions about the role of domestic political factors. Using systematic qualitative primary research and employing elite interviewing and process tracing, this paper aims to fill this gap for the period of the Partido Socialista Obrero Español (PSOE) administration. The paper shows that domestic politics played a crucial role in the management of the crisis, most importantly by determining the shape of the measures undertaken. In its three distinct stages – downplaying/inaction, reaction/stimulus, and austerity/reform – the PSOE's response was certainly constrained by external factors, most notably EMU membership and the actions of sovereign-bond investors, the ECB and Germany. Yet while these external constraints forced the government to act, domestic political factors fundamentally shaped the content of key measures: the fiscal stimulus, the labour, financial and pension reforms, the refusal to accept a bailout or the reform of the Constitution. Seven factors were particularly influential: i) electoral and political cost, ii) party and partisanship, iii) organised interests, iv) domestic institutions, v) ideological preferences, vi) ineffective decision-making, and vii) judgement and personal characteristics of decision-makers. In conclusion, domestic politics played an important role in the management of the crisis, a role that has been underestimated by dominant approaches focusing on external constraints and weak domestic policy autonomy. The findings provide empirical evidence to support research agendas that identify significant state discretion in the face of international economic integration and an important role for domestic political factors such as institutions, material interests, partisanship and ideology in shaping economic outcomes.Keywords: economic crisis, Euro, PSOE, Spain
Procedia PDF Downloads 1203339 Gender Equality and the Politics of Presence among the Maasai in Kenya
Authors: Shillah Memusi
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Underrepresentation of women in governance structures is a global phenomenon, with patriarchal considerations being among the main, if not the top, reason for this in Sub Saharan Africa. This paper demonstrates that gender norms and informal rules have perpetuated a culture of stereotypical gender roles that have limited women’s public participation and leadership in society. To achieve this, the paper explores barriers to women’s political engagement, and how these are navigated in the face of gender equality laws. Situated in Kenya’s Maasai community, the paper investigates the influence of set laws on the increased involvement of women from the patriarchal community in the political economy. It gives special attention to the intersectionality of formal and informal laws and the subsequent interpretation and implementation of gender equality. The paper then concludes by demonstrating the benefits of exploring alternative gender equality pathways, as informed by contextual realities of settings such as patriarchal communities.Keywords: equality, Kenya, patriarchy, public participation, women
Procedia PDF Downloads 2993338 Short-Term versus Long-Term Effect of Waterpipe Smoking Exposure on Cardiovascular Biomarkers in Mice
Authors: Abeer Rababa'h, Ragad Bsoul, Mohammad Alkhatatbeh, Karem Alzoubi
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Introduction: Tobacco use is one of the main risk factors to cardiovascular diseases (CVD) and atherosclerosis in particular. WPS contains several toxic materials such as: nicotine, carcinogens, tar, carbon monoxide and heavy metals. Thus, WPS is considered to be as one of the toxic environmental factors that should be investigated intensively. Therefore, the aim of this study is to investigate the effect of WPS on several cardiovascular biological markers that may cause atherosclerosis in mice. The study also conducted to study the temporal effects of WPS on the atherosclerotic biomarkers upon short (2 weeks) and long-term (8 weeks) exposures. Methods: mice were exposed to WPS and heart homogenates were analyzed to elucidate the effects of WPS on matrix metalloproteinase (MMPs), endothelin-1 (ET-1) and, myeloperoxidase (MPO). Following protein estimation, enzyme-linked immunosorbent assays were done to measure the levels of MMPs (isoforms 1, 3, and 9), MPO, and ET-1 protein expressions. Results: our data showed that acute exposure to WPS significantly enhances the levels of MMP-3, MMP- 9, and MPO expressions (p < 0.05) compared to their corresponding control. However, the body was capable to normalize the level of expressions for such parameters following continuous exposure for 8 weeks (p > 0.05). Additionally, we showed that the level of ET-1 expression was significantly higher upon chronic exposure to WPS compared to both control and acute exposure groups (p < 0.05). Conclusion: Waterpipe exposure has a significant negative effect on atherosclerosis and the enhancement of the atherosclerotic biomarkers expression (MMP-3 and 9, MPO, and ET-1) might represent an early scavenger of compensatory efforts to maintain cardiac function after WP exposure.Keywords: atherosclerotic biomarkers, cardiovascular disease, matrix metalloproteinase, waterpipe
Procedia PDF Downloads 3503337 Osteogenesis in Thermo-Sensitive Hydrogel Using Mesenchymal Stem Cell Derived from Human Turbinate
Authors: A. Reum Son, Jin Seon Kwon, Seung Hun Park, Hai Bang Lee, Moon Suk Kim
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These days, stem cell therapy is focused on for promising source of treatment in clinical human disease. As a supporter of stem cells, in situ-forming hydrogels with growth factors and cells appear to be a promising approach in tissue engineering. To examine osteogenic differentiation of hTMSCs which is one of mesenchymal stem cells in vivo in an injectable hydrogel, we use a methoxy polyethylene glycol-polycaprolactone blockcopolymer (MPEG-PCL) solution with osteogenic factors. We synthesized MPEG-PCL hydrogel and measured viscosity to check sol-gel transition. In order to demonstrate osteogenic ability of hTMSCs, we conducted in vitro osteogenesis experiment. Then, to confirm the cell cytotoxicity, we performed WST-1 with hTMSCs and MPEG-PCL. As the result of in vitro experiment, we implanted cell and hydrogel mixture into animal model and checked degree of osteogenesis with histological analysis and amount of expression genes. Through these experimental data, MPEG-PCL hydrogel has sol-gel transition in temperature change and is biocompatible with stem cells. In histological analysis and gene expression, hTMSCs are very good source of osteogenesis with hydrogel and will use it to tissue engineering as important treatment method. hTMSCs could be a good adult stem cell source for usability of isolation and high proliferation. When hTMSCs are used as cell therapy method with in situ-formed hydrogel, they may provide various benefits like a noninvasive alternative for bone tissue engineering applications.Keywords: injectable hydrogel, stem cell, osteogenic differentiation, tissue engineering
Procedia PDF Downloads 4453336 Single Pass Design of Genetic Circuits Using Absolute Binding Free Energy Measurements and Dimensionless Analysis
Authors: Iman Farasat, Howard M. Salis
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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement
Procedia PDF Downloads 4723335 Quantitative Analysis of Orphan Nuclear Receptors in Insulin Resistant C2C12 Skeletal Muscle Cells
Authors: Masocorro Gawned, Stephen Myers, Guat Siew Chew
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Nuclear Receptors (NR) are a super family of transcription factors that play a major role in lipid and glucose metabolism in skeletal muscle. Recently, pharmacological evidence supports the view that stimulation of nuclear receptors alleviates Type 2 Diabetes (T2D). The orphan nuclear receptors (ONR) are members of the nuclear receptor (NR) superfamily whose ligands and physiological functions remain unknown. To date, no systematic studies have been carried out to screen for ONRs expressed in insulin resistant (IR) skeletal muscle cells. Therefore, in this study, we have established a model for IR by treating C2C12 skeletal muscle cells with insulin (10nM) for 48 hours. Western Blot analysis of phosphorylated AKT confirmed IR. Real-time quantitative polymerase chain reaction (qPCR) results highlighted key ONRs including NUR77 (NR4A1), NURR1 (NR4A2) and NOR1 (NR4A3) which have been associated with fatty acid oxidation regulation and glucose homeostasis. Increased mRNA expression levels of estrogen-related receptors (ERRs), REV-ERBα, NUR77, NURR1, NOR1, in insulin resistant C2C12 skeletal muscle cells, indicated that these ONRs could potentially play a pivotal regulatory role of insulin secretion in lipid metabolism. Taken together, this study has successfully contributed to the complete analysis of ONR in IR, and has filled in an important void in the study and treatment of T2D.Keywords: type 2 diabetes, orphan nuclear receptors, transcription receptors, quantitative mRNA expression
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