Search results for: fibernectin expression

Authors: Isha Ranadive, Sonam Patel, Suresh Balakrishnan

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It has been observed that in lizards wound can be healed by either a scar free mechanism or by scarring. The animal model used to study both these healing processes was Northern House Gecko. In lizard, the tail when amputated heals by scar free mechanism which allows it to regenerate, the same is not seen when the limb is amputated. Proliferation, apoptosis, and angiogenesis are the main events which succeed an injury. We observed that proliferation of the cells beneath the wound epidermis was much higher in case of wound healing in tail. This could be because after the wound gets covered by the epithelium, it enters in to a cross-talk with the underlying mesenchyme to recruit a pool of blastemal cells which proliferate and later differentiate to form the lost part through epimorphic regeneration. This was substantiated by mRNA expression levels of various FGFs which facilitate the cross-talk and also by PCNA which is a marker for proliferation. Western blot result reaffirms the same notion. However, in case of the limb, the rate of apoptosis was more than proliferation as there are a lot of debris that needs to be removed. We came to this conclusion as we observed that p53 the apoptotic gene was highly upregulated in case of the scarred tissue. Further, we confirmed this result by checking the anti-apoptotic gene bcl2 and found it to be significantly down-regulated. As we noticed heightened proliferation in the case of scar-free wound healing in tail, angiogenesis was targeted for the study. This is because, when the cells are proliferating they require constant supply of blood and hence neo-vascularization is inevitable. It was observed that the marker of angiogenesis, VEGF, was expressed more during wound healing as compared to the resting stage of tail. Moreover, a high up-regulation was seen in KDR, a receptor of VEGF. Thus, this study reveals how proliferation, apoptosis, and angiogenesis play a key role in the scar-free as well as scarred wound healing.

Keywords: epimorphic regeneration, injury, northern house gecko, wound healing

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Authors: Ibrahim M. Mehedi, Uzair Ansari, Ubaid M. Al-Saggaf, Abdulrahman H. Bajodah

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This paper presents a methodology for balancing a rotary inverted pendulum system using Robust Generalized Dynamic Inversion (RGDI) under influence of parametric variations and external disturbances. In GDI control, dynamic constraints are formulated in the form of asymptotically stable differential equation which encapsulates the control objectives. The constraint differential equations are based on the deviation function of the angular position and its rates from their reference values. The constraint dynamics are inverted using Moore-Penrose Generalized Inverse (MPGI) to realize the control expression. The GDI singularity problem is addressed by augmenting a dynamic scale factor in the interpretation of MPGI which guarantee asymptotically stable position tracking. An additional term based on Sliding Mode Control is appended within GDI control to make it robust against parametric variations, disturbances and tracking performance deterioration due to generalized inversion scaling. The stability of the closed loop system is ensured by using positive definite Lyapunov energy function that guarantees semi-global practically stable position tracking. Numerical simulations are conducted on the dynamic model of rotary inverted pendulum system to analyze the efficiency of proposed RGDI control law. The comparative study is also presented, in which the performance of RGDI control is compared with Linear Quadratic Regulator (LQR) and is verified through experiments. Numerical simulations and real-time experiments demonstrate better tracking performance abilities and robustness features of RGDI control in the presence of parametric uncertainties and disturbances.

Keywords: generalized dynamic inversion, lyapunov stability, rotary inverted pendulum system, sliding mode control

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Authors: S. S. Singh, A. Bhattacharya, S. Bhattacharya

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The eukaryotic exosome complex plays a pivotal role in RNA biogenesis, maturation, surveillance and differential expression of various RNAs in response to varying environmental signals. The exosome is composed of evolutionary conserved nine core subunits and the associated exonucleases Rrp6 and Rrp44. Rrp6p is crucial for the processing of rRNAs, other non-coding RNAs, regulation of polyA tail length and termination of transcription. Rrp6p, a 3’-5’ exonuclease is required for degradation of 5’-external transcribed spacer (ETS) released from the rRNA precursors during the early steps of pre-rRNA processing. In the parasitic protist Entamoeba histolytica in response to growth stress, there occurs the accumulation of unprocessed pre-rRNA and 5’ ETS sub fragment. To understand the processes leading to this accumulation, we looked for Rrp6 and the exosome subunits in E. histolytica, by in silico approaches. Of the nine core exosomal subunits, seven had high percentage of sequence similarity with the yeast and human. The EhRrp6 homolog contained exoribonuclease and HRDC domains like yeast but its N- terminus lacked the PMC2NT domain. EhRrp6 complemented the temperature sensitive phenotype of yeast rrp6Δ cells suggesting conservation of biological activity. We showed 3’-5’ exoribonuclease activity of EhRrp6p with in vitro-synthesized appropriate RNAs substrates. Like the yeast enzyme, EhRrp6p degraded unstructured RNA, but could degrade the stem-loops slowly. Furthermore, immunolocalization revealed that EhRrp6 was nuclear-localized in normal cells but was diminished from nucleus during serum starvation, which could explain the accumulation of 5’ETS during stress. Our study shows functional conservation of EhRrp6p in E.histolytica, an early-branching eukaryote, and will help to understand the evolution of exosomal components and their regulatory function.

Keywords: entamoeba histolytica, exosome complex, rRNA processing, Rrp6

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Authors: Ayşen Bakioğlu, Gökçen Seyra Çakır

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This study aims to explore how research assistants who work in project teams experience team member autonomy and how they reconcile team member autonomy with team collaboration. The study utilizes snowball sampling. 20 research assistants who work the faculties of education in Marmara University and Yıldız Technical University have been interviewed. The analysis of data involves a content analysis MAXQDAPlus 11 which is a qualitative data analysis software is used as the data analysis tool. According to the findings of this study, emerging themes include team norm formation, team coordination management, the role of individual tasks in team collaboration, leadership distribution. According to the findings, interviewees experience team norm formation process in terms of processes, which pertain to task fulfillment, and processes, which pertain to the regulation of team dynamics. Team norm formation process instills a sense of responsibility amongst individual team members. Apart from that, the interviewees’ responses indicate that the realization of the obligation to work in a team contributes to the team norm formation process. The participants indicate that individual expectations are taken into consideration during the coordination of the team. The supervisor of the project team also has a crucial role in maintaining team collaboration. Coordination problems arise when an individual team member does not relate his/her academic field with the research topic of the project team. The findings indicate that the leadership distribution in the project teams involves two leadership processes: leadership distribution which is based on the processes that focus on individual team members and leadership distribution which is based on the processes that focus on team interaction. Apart from that, individual tasks serve as a facilitator of collaboration amongst team members. Interviewees also indicate that individual tasks also facilitate the expression of individuality.

Keywords: project teams in higher education, research assistant teams, team collaboration, team member autonomy

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Authors: Shahla Bukhtair

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A paradigm presents a consensus view of a particular or collective community, accepted into by the members of that community, either consciously pronounced or, more likely, simply assumed and not intentionally acknowledged but is articulated. Paradigm shift is based on the behavioral attitude of the community. Change is inexorable. The world is suffering with the innovative creation of globalization. Media boosted this paradigm shift all over the world. Globalization is a vigorous process which impacts differentially on various cultures around the world. The outcome of the globalization is permeates cultural boundaries and in the process results in the spread of Western ideologies and values across the world. The term flourished in 20th century. Globalization is regarded as having substantial impact on such crises through its encouragement of conflicts rather than conciliation; through opportunities of expression, various groups get benefit with it. Identity crisis refers to inflexible mechanism i.e. cultural and political conflicts among polarized groups, which struggle with each other over the definition of a national identity. Violence is not only a kind of physical but it also psychological as well. Due to identity crisis, a person is having an issue of fear, anxiety, and lack of security. Everything has negative and positive aspects. Newspaper columns, magazine articles, films, made-for-TV movies, television special reports, and talk shows are all public arenas where images of political agenda of their own interest are constructed, debated, and reproduced. From these resources, individuals construct their own conceptions of what is normal and acceptable. This bias affects images in the media, and in turn has a negative effect on public development in a society. This paper investigates the relationship between globalization and cultural war, identity crisis and the role of violence. Objectives: - To determine which type of media plays an important role in shaping perceptions and attitudes of public negatively; - To analyze the impact of globalization on identity crisis, violence and global culture (positive and negative).

Keywords: paradigm shift, globalization, identity crisis, cultural war

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Authors: Sachin Sharma

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Sexual consent is integral to every sexual relationship. It is a process to facilitate sexual autonomy and bodily integrity. It assures complete sexual personhood and allows an individual to explore her sexual expressions independently. But the said proposition is not true for people with psychosocial disabilities. Generally, they are considered seraphic or mephistophelic and denied access to sexual autonomy. This result in institutionalizing the sexuality of disabled persons, where the eugenics-ableist narrative defines assessment and access to consent. This way, sexuality and disability are distanced apart. It is primarily due to the stigmatized socio-cultural constructs of sexuality that define sex within a “standard” and “charmed” circle. Such stigmatized expression influences the law, as it considers people with psychosocial disabilities incapable of sexual consent. The approach of legal institutions is very narrow towards interpreting their sexual rights. It echoes the modernist-ableism and strangulates the sexual choices. This way, it reflects the repressive model of sex and denies space to people with psychosocial disabilities. Moreover, judicial courts follow old and conservative methods while dealing with sexual issues. For instance, courts still practice the “standardized” norm of intelligence quotient (IQ) for determining the credibility of persons with psychosocial disabilities. Further, there is still doubt about assistive communicative techniques. This paper will try to question the normative structure of sexual consent and related laws while specifically addressing the issues of sex as desire and abuse. Considering the commitment to the United Nations Convention on the Rights of Persons with Disabilities (herein referred to as UNCRPD) and common law experience, the paper will draw a comparative study on the legal position of sexual rights in India. The paper will also analyze the role of UNCRPD in addressing sexual rights. The author will examine the position of sexual rights of people with psychosocial disabilities after the drafting of UNCRPD and specific state laws. The paper primarily follows the doctrinal method.

Keywords: sexual autonomy, institutionalized choices, overregulated laws, violation of individuality

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Authors: S. Subramaniam, J. S. A. Rao, P. Ramdas, K. R. Selvaduray, N. M. Han, M. K. Kutty, A. K. Radhakrishnan

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Immune system is a complex system where the immune cells have the capability to respond against a wide range of immune challenges including cancer progression. However, in the event of cancer development, tumour cells trigger immunosuppressive environment via activation of myeloid-derived suppressor cells and T regulatory (Treg) cells. The Treg cells are subset of CD4+ T lymphocytes, known to have crucial roles in regulating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Dysregulation of these mechanisms could lead to cancer progression and immune suppression. Recently, there are many studies reporting on the effects of natural bioactive compounds on immune responses against cancer. It was known that tocotrienol-rich-fraction consisting 70% tocotrienols and 30% α-tocopherol is able to exhibit immunomodulatory as well as anti-cancer properties. Hence, this study was designed to evaluate the effects of gamma-tocotrienol (G-T3) supplementation on T-reg cells in a syngeneic mouse model of breast cancer. In this study, female BALB/c mice were divided into two groups and fed with either soy oil (vehicle) or gamma-tocotrienol (G-T3) for two weeks followed by inoculation with tumour cells. All the mice continued to receive the same supplementation until day 49. The results showed a significant reduction in tumour volume and weight in G-T3 fed mice compared to vehicle-fed mice. Lung and liver histology showed reduced evidence of metastasis in tumour-bearing G-T3 fed mice. Besides that, flow cytometry analysis revealed T-helper cell population was increased, and T-regulatory cell population was suppressed following G-T3 supplementation. Moreover, immunohistochemistry analysis showed that there was a marked decrease in the expression of FOXP3 in the G-T3 fed tumour bearing mice. In conclusion, the G-T3 supplementation showed good prognosis towards breast cancer by enhancing the immune response in tumour-bearing mice. Therefore, gamma-T3 can be used as immunotherapy agent for the treatment of breast cancer.

Keywords: breast cancer, gamma tocotrienol, immune suppression, supplement

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Authors: Atena Sadat Hosseini, Mohammadhossein Habibi

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Acute myeloid leukemia (AML) is the most typically diagnosed leukemia. In older adults, AML imposes a dismal outcome. AML originates with a dominant mutation, then adds collaborative, transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Several chemotherapeutic drugs are used for this cancer. These drugs are naturally associated with several side effects, and finding a more accurate molecular mechanism of these drugs can have a significant impact on the selection and better candidate of drugs for treatment. In this study, we evaluated bortezomibin myeloma cells using bioinformatics analysis and evaluation of RNA-Seq data. Then investigated the molecular pathways proteins- proteins interactions associated with this chemotherapy drug. A total of 658upregulated genes and 548 downregulated genes were sorted.AUF1 (hnRNP D0) binds and destabilizes mRNA, degradation of GLI2 by the proteasome, the role of GTSE1 in G2/M progression after G2 checkpoint, TCF dependent signaling in response to WNT demonstrated in upregulated genes. Besides insulin resistance, AKT phosphorylates targets in the nucleus, cytosine methylation, Longevity regulating pathway, and Signal Transduction of S1P Receptor were related to low expression genes. With respect to this results, HIST2H2AA3, RP11-96O20.4, ZED9, PRDX1, and DOK2, according to node degrees and betweenness elements candidates from upregulated genes. in the opposite side, PYURF, NRSN1, FGF23, UPK3BL, and STAG3 were a prominent role in downregulated genes. Sum up, Using in silico analysis in the present study, we conducted a precise study ofbortezomib molecular mechanisms in myeloma cells. so that we could take further evaluation to discovermolecular cancer therapy. Naturally, more additional experimental and clinical procedures are needed in this survey.

Keywords: myeloma cells, acute myeloid leukemia, bioinformatics analysis, bortezomib

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Authors: Yosra Ben Salah, Wang Li Jun, Salem Bellil

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The village Hammem Zriba is a lost little paradise in the middle of a beautiful landscape that captures the eyes of every visitor. The village alone is a rich expression of different elements such as urban, architecture, technical and vernacular elements, as well as sociological, spiritual and religious behaviors. This heritage is in degrading conditions and is threatened by disappearing soon; thus, actions have to be taken as soon as possible to preserve this heritage, record, analyze and learn from its traditional ways of construction. The strategy of this study is to examine the architecture within the Berber society over a period of time and influenced by a certain location and its relationship to the social and cultural aspects; this research will focus on historical, environmental, social and cultural aspects influencing architecture. The contents of this paper should mainly be constructed by three successive layouts of historical view, a cultural view and an architectural view that will include the urban and domestic scale. This research relies on the integration of both theoretical and empirical investigations. On the theoretical level: A documentary analysis of secondary data is used. Documentary analysis means content analysis of the relevant documents that include books, journals, magazines, archival data, and field survey and observations. On the empirical level: analysis of these traditional ways of planning and house building will be carried out. Through the Analysis, three techniques will be employed to collect primary data. These techniques are; systematic analysis of the architectural drawings, quantitative analysis to the houses statistics, and a direct observation. Through this research, the technical, architectural and urban achievements of the Berber people who represent a part of the general history and architectural history will be emphasized. And on a second point the potential for the sustainability present in this traditional urban planning and housing to be used to formulate guidelines for modern urban and housing development.

Keywords: culture, history, traditional architecture, values

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Authors: Abul B. M. M. K. Islam, Mandar Dave, Roderick V. Jensen, Ashok R. Amin

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A systems approach was applied to characterize differentially expressed transcripts, bioinformatics pathways, and proteins and prostaglandins (PGs) from lung fibroblasts procured from wild-type (WT), COX-1-/- and COX-2-/- mice to understand system level control mechanism. Bioinformatics analysis of COX-2 and COX-1 ablated cells induced COX-1 and COX-2 specific signature respectively, which significantly overlapped with an 'IL-1β induced inflammatory signature'. This defined novel cross-talk signals that orchestrated coordinated activation of pathways of sterile inflammation sensed by cellular stress. The overlapping signals showed significant over-representation of shared pathways for interferon y and immune responses, T cell functions, NOD, and toll-like receptor signaling. Gene Ontology Biological Process (GOBP) and pathway enrichment analysis specifically showed an increase in mRNA expression associated with: (a) organ development and homeostasis in COX-1-/- cells and (b) oxidative stress and response, spliceosomes and proteasomes activity, mTOR and p53 signaling in COX-2-/- cells. COX-1 and COX-2 showed signs of functional pathways committed to cell cycle and DNA replication at the genomics level. As compared to WT, metabolomics analysis revealed a significant increase in COX-1 mRNA and synthesis of basal levels of eicosanoids (PGE2, PGD2, TXB2, LTB4, PGF1α, and PGF2α) in COX-2 ablated cells and increase in synthesis of PGE2, and PGF1α in COX-1 null cells. There was a compensation of PGE2 and PGF1α in COX-1-/- and COX-2-/- cells. Collectively, these results support a broader, differential and collaborative regulation of both COX-1 and COX-2 pathways at the metabolic, signaling, and genomics levels in cellular homeostasis and sterile inflammation induced by cellular stress.

Keywords: cyclooxygenases, inflammation, lung fibroblasts, systemic

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Authors: Alsulami H., Alghamdi N., Alasker A., Almohen N., Shome D.

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Most conventional chemotherapeutic agents, which are used for the treatment of cancers, not only eradicate cancer cells but also affect normal hematopoietic Stem cells (HSCs) that lead to severe pancytopenia during treatment. Therefore, a need exists for distinct approaches to treat cancer without or with minimum effect on normal HSCs. Parthenolide (PTL), a herbal product occurring naturally in the plant Feverfew, is a potential chemotherapeutic agent for the treatment of many cancers, such as acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). In this study we investigated the effect of different PTL concentrations on the viability of normal HSCs and also on the ability of these cells to form colonies after they have been treated with PTL in vitro. Methods: Normal 24 bone marrow and cord blood samples were included in this study after obtaining informed consent. The mononuclear cells were isolated using density gradient separation. Cells were cultured with different PTL concentrations for 24 hours. Post-culture cell viability was assessed using 7ADD in a flow cytometry-based test. In addition, a colony-forming unit assay (CFU) was carried out to assess the effect of PTL on HSCs. the expression of NFҝB was also assessed using a PE-labeled anti-pNFκBP65 antibody. Results: This study showed that there was no statistically significant difference in the percentage of cell death between untreated and PTL-treated cells with 5 μM PTL (p = 0.7), 10 μM PTL (p = 0.4) and 25 μM (p = 0.09) respectively. However, at higher doses, PTL caused a significant increase in the percentage of cell death. These results were significant when compared to untreated control (p < 0.001). The response of cord blood cells (n=4), on the other hand, was slightly different from that for bone marrow cells in that the percentage of cell death was significant at 100 μM PTL. Therefore, cord blood cells seemed more resistant than bone marrow cells. Conclusion: At concentrations ≤25 μM, PTL has a minimum or no effect on HSCs in vitro. Cord blood HSCs are more resistant to PTL compared to bone marrow HSCs.

Keywords: stem cell, parthenolide, ALL, NFKB

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Authors: Alejandro Arnaldo Barroso Martinez

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Unlike sex, which is constituted by anatomic-physiological differences, gender is a social construction. Our thoughts and behaviors as females and males are not etched in stone by our biology but rather from how society expects us to think and behave based on our sex assignment in the womb. Social expectations, values, and roles are taken on by individuals and shape the ways considered acceptable and linked to our bodies, feelings, and interpersonal relationships. Furthermore, these evolve into dire consequences for those who do not meet these disciplinary, economic, and cultural standards. Then, the social learning of gender identity implies the individual’s psychological sense of being, and it might be highly linked to a sense of life and suicide attempts. As a result, suicide has been considered a gender issue with differences in the rates and means used by men and women worldwide. Nevertheless, there has been a misunderstanding of the meaning of being male or female in a particular context and how it becomes a risk process for suicide attempts. For this reason, the general objective of the current research is to explain how this process occurs in Cuba. From a Critical Sociology and Social Psychology, a qualitative methodology was developed through six case studies and qualitative in-depth interviews. The analysis is focused on the sequence and interplay between two dimensions of meaning: signifiers and voices. Findings show that the risk process of suicide attempts in Cuba means some patriarchal beliefs and practices as part of informal educational models and some positivist practices in mental health attention. Findings also show that community relations create a sense of belonging, and it is a protection against suicide attempts in Cuba. Those frames of signifiers and voices explain in both males and females but differently when and how they are suffering from isolation, violence, the normalization of emotional awareness, and emotional distress expression. Suicide prevention programs should take gender learning into account as a cultural process.

Keywords: social constructions, gender identity, meanings, suicide attempt

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Authors: Chandrabati Chakraborty

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The progressive emergence, in the course of the evolution of life, mind and personality, requires us to assume a creative Principle operating timeless Reality in the temporal. The difference between Western philosophy and that of India, concerns the origin and the purpose of the philosophical enquiry. While the former wonders at the external world, the latter is awareness of perennial suffering associated with human existence. The present world suffers from a basic form of rootlessness,reflecting many psychological, philosophical studies. Alienation,a major theme of human condition in the contemporary epoch has emerged as natural consequences of existential predicament. As Edmund Fuller also observes that individuals suffer not only from famine, ruin or even war but also from devastating inner problems, which are that of estrangement, hopelessness and utter despair. This existentialism is thus considered by Jean Wahl as the “Philosophies of existence”.The post world war scenario well analyses the chaos,annihilation,frustration and anguished estrangement. In such conditions when the West cries out , “What is there?I know first of all that I am.But who am I?.....I am sepeated.What I am seperated from I cannot name it. But I am seperated.”(Dostoevsky:The Confession), Vedantic philosophy looks upon the Pilgrim’s Progress of Humanity as being essentially one,operationg squarely within the bounds of reality, reflecting a basic human experience, outbraving indecorous dictims that have failed to give due honour to human beings,echoing for centuries the Sanskrit slokas with ultimate certitude: II Esa Atma samaha plusina samo masakena samo nagena sama ebhis tribhir lokaih.....sama nena sarvena II (The Atman (Divine Soul) is the same in the ant, the same in the gnat, the same in the elephant, the same in these three worlds....the same in the whole Universe). The present paper aims at a comparative study of cultural and philosophical expression taking into view extensive illustrations from Western Philosophers and The Vedantic,Upanishadic lores of Indian philosophy.

Keywords: existentialism, Vedanta, philosophy, absurdism

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Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

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Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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Authors: Carlo Cogliati

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The study of the relationship of philosophical reason with the religious domain has been very much a concern for many of the Western philosophical and theological traditions. In this essay, I will suggest a proposal for an Eastern philosophy of religion based on Nishida’s contradictory identity of the two: philosophy soku hi (is, and yes is not) religion. This will pose a challenge to the traditional Western contents and methods of the discipline. This paper aims to serve three purposes. First, I will critically assess Charlesworth’s typology of the relation between philosophy and religion in the West: philosophy as/for/against/about/after religion. I will also engage Harrison’s call for a global philosophy of religion(s) and argue that, although it expands the scope and the range of the questions to address, it is still Western in its method. Second, I will present Nishida’s logic of absolutely contradictory self-identity as the instrument to transcend the dichotomous pair of identity and contradiction: ‘A is A’ and ‘A is not A’. I will then explain how this ‘concrete’ logic of the East, as opposed to the ‘formal’ logic of the West, exhibits at best the bilateral dynamic relation between philosophy and religion. Even as Nishida argues for the non-separability of the two, he is also aware and committed to their mutual non-reducibility. Finally, I will outline the resulting new relation between God and creatures. Nishida in his philosophy soku hi religion replaces the traditional Western dualistic concept of God with the Eastern non-dualistic understanding of God as “neither transcendent nor immanent, and at the same time both transcendent and immanent.” God is therefore a self-identity of contradiction, nowhere and yet everywhere present in the world of creatures. God as absolute being is also absolute nothingness: the world of creatures is the expression of God’s absolute self-negation. The overreaching goal of this essay is to offer an alternative to traditional Western approaches to philosophy of religion based on Nishida’s logic of absolutely contradictory self-identity, as an example of philosophical and religious counter(influence). The resulting relationship between philosophy and religion calls for a revision of traditional concepts and methods. The outcome is not to reformulate the Eastern predilection to not sharply distinguish philosophical thought from religious enlightenment rather to bring together philosophy and religion in the place of identity and difference.

Keywords: basho, Nishida Kitaro, shukyotetsugaku, soku hi, zettai mujunteki jikodoitsu no ronri

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Authors: Hediyeh Talebi, Shokoofeh Ghiam, Changiz Eslahchi

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Traditionally, Alzheimer’s disease research has focused on genes with significant fold changes, potentially neglecting subtle but biologically important alterations. Our study introduces an integrative approach that highlights genes crucial to underlying biological processes, regardless of their fold change magnitude. Alzheimer's Single-cell RNA-seq data related to the peripheral blood mononuclear cells (PBMC) was extracted from the Gene Expression Omnibus (GEO). After quality control, normalization, scaling, batch effect correction, and clustering, differentially expressed genes (DEGs) were identified with adjusted p-values less than 0.05. These DEGs were categorized based on cell-type, resulting in four datasets, each corresponding to a distinct cell type. To distinguish between cells from healthy individuals and those with Alzheimer's, an adversarial autoencoder with a classifier was employed. This allowed for the separation of healthy and diseased samples. To identify the most influential genes in this classification, the weight matrices in the network, which includes the encoder and classifier components, were multiplied, and focused on the top 20 genes. The analysis revealed that while some of these genes exhibit a high fold change, others do not. These genes, which may be overlooked by previous methods due to their low fold change, were shown to be significant in our study. The findings highlight the critical role of genes with subtle alterations in diagnosing Alzheimer's disease, a facet frequently overlooked by conventional methods. These genes demonstrate remarkable discriminatory power, underscoring the need to integrate biological relevance with statistical measures in gene prioritization. This integrative approach enhances our understanding of the molecular mechanisms in Alzheimer’s disease and provides a promising direction for identifying potential therapeutic targets.

Keywords: alzheimer's disease, single-cell RNA-seq, neural networks, blood biomarkers

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Authors: R. Stalin, D. Karthick, H. Haseena Banu, T. P. Sachidanandam, P. Shanthi

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Background: Breast cancer is emerging as one of the leading cause of cancer related deaths and hence there arises the need to look out for drugs which are more targets specific with minimal side effects. In recent times, there is a shift towards alternative medicine due to low cost and less side effects. Siddha system of medicine is one the oldest system of medicine practiced against various ailments. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio (TD) and its anticancer potential is evaluated in terms of induction of apoptosis. Objective: The present study was designed to investigate the anti proliferative effect of TD and 1,2,3,4,6-penta-O-galloyl-b-D-glucose (PGG), a pure compound isolated from TD on human mammary carcinoma cell line (MCF-7). Materials and Methods: Cell viability was studied using MTT analysis and trypan blue staining. Mitochondrial membrane potential was studied using DAPI staining. The protein and mRNA expressions of pro-apoptotic and anti- apoptotic markers namely Bax, Bad, Bcl-2 and caspases were also assessed by Western Blotting and RT PCR. Results: Viability studies of TD and PGG treated MCF-7 cells showed an inhibition in cell growth in time and dose dependent manner. The alteration in mitochondrial membrane potential was restored through treatment with TD and PGG which was confirmed by DAPI staining. The protein and mRNA expression of pro-apoptotic markers was found to be significantly increased in TD and PGG treated cells with a concomitant decrease in anti-apoptotic markers. Conclusion: The results of the study suggest that TD and PGG exhibit their anticancer effect through its membrane stabilizing property and activation of apoptotic cascade in MCF-7 cells.

Keywords: apoptosis, mammary carcinoma, MCF-7, penta galloyl glucose, Tridham

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Authors: Ahmed A. Sedik, Doaa Mahmoud Shuaib

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Brain injury is a cause of disability and death worldwide. Potassium dichromate (PD) is an environmental contaminant widely recognized as teratogenic, carcinogenic, and mutagenic towards animals and humans. The aim of the present study was to investigate the possible neuroprotective effects of tangeretin (TNG) on PD-induced brain injury in rats. Forty male adult Wistar rats were randomly and blindly allocated into four groups (8 rats /group). The first group received saline intranasally (i.n.). The second group received a single dose of PD (2 mg/kg, i.n.). The third group received TNG (50 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. Four groups received TNG (100 mg/kg; orally) for 14 days, followed by i.n. of PD on the last day of the experiment. 18- hours after the final treatment, behavioral parameters, neuro-biochemical indices, FTIR analysis, and histopathological studies were evaluated. Results of the present study revealed that rats intoxicated with PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in Nrf2 signaling pathway and GSH levels with an increase in brain contents of TNF-α, IL-10, and NF-kβ and reduced AKT levels in brain homogenates. Treatment with TNG (100 mg/kg; orally) ameliorated behavioral, cholinergic activities and oxidative stress, decreased the elevated levels of pro-inflammatory mediators; TNF-α, IL-10, and NF-κβ elevated AKT pathway with corrected FTIR spectra with a decrease in brain content of chromium residues detected by atomic absorption spectrometry. Also, TNG administration restored the morphological changes as degenerated neurons and necrosis associated with PD intoxication. Additionally, TNG decreased Caspase-3 expression in the brain of PD rats. TNG plays a crucial role in AKT/Nrf2 pathway that is responsible for their antioxidant, anti-inflammatory effects, and apoptotic pathway against PD-induced brain injury in rats.

Keywords: tangeretin, potassium dichromate, brain injury, AKT/Nrf2 signaling pathway, FTIR, atomic absorption spectrometry

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Authors: Simont Toussi

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Cameroon and the Central African Republic arebound by the provisions of many regional and international charters, which condemn the manipulation of information, obstacles to access reliable information, or the limitation of freedoms of expression and opinion. These two countries also have constitutional guarantees for free speech and access to true and liable information. However, they are yet to define specific policies and regulations for access to information, disinformation, or misinformation. Yet, certain countries’ laws and regulations related to information and communication technologies, to criminal procedures, to terrorism, or intelligence services contain provisions that rather hider human rights by condemning false information. Like many other African countries, Cameroon and the Central African Republic face a profound democratic regression, and governments use multiple methods to stifle online discourse and digital rights. Despite the increased uptake of digital tools for political participation, there is a lack of interactivity and adoption of these tools. This enables a scarcity of information and creates room for the spreading of disinformation in the public space, hamperingdemocracy and the respect for human rights. This research aims to analyse the adequacy of stakeholders’ responses to disinformation in Cameroon and the Central African Republic in periods of political contestation, such as elections and anti-government protests, to highlight the nature, perpetrators, strategies, and channels of disinformation, as well as its effects on democratic actors, including civil society, bloggers, government critics, activists, and other human rights defenders. The study follows a qualitative method with literature review, content analysis, andkey informant’sinterviews with stakeholders’ representatives, emphasized crowdsourcing as a data and information collecting method in the two countries.

Keywords: disinformation, democracy, political manipulation, social media, media, fake news, central Africa, cameroon, misinformation, free speech

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Authors: Ahmad Ali Shahid, Mukhtar Ahmed

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The demand for long staple fiber having better strength and length is increasing with the introduction of modern spinning and weaving industry in Pakistan. Work on gene discovery from developing cotton fibers has helped to identify dozens of genes that take part in cotton fiber development and several genes have been characterized for their role in fiber development. Sucrose synthase (SuS) is a key enzyme in the metabolism of sucrose in a plant cell, in cotton fiber it catalyzes a reversible reaction, but preferentially converts sucrose and UDP into fructose and UDP-glucose. UDP-glucose (UDPG) is a nucleotide sugar act as a donor for glucose residue in many glycosylation reactions and is essential for the cytosolic formation of sucrose and involved in the synthesis of cell wall cellulose. The study was focused on successful Agrobacterium-mediated stable transformation of SuS gene in pCAMBIA 1301 into cotton under a CaMV35S promoter. Integration and expression of the gene were confirmed by PCR, GUS assay, and real-time PCR. Young leaves of SuS overexpressing lines showed increased total soluble sugars and plant biomass as compared to non-transgenic control plants. Cellulose contents from fiber were significantly increased. SEM analysis revealed that fibers from transgenic cotton were highly spiral and fiber twist number increased per unit length when compared with control. Morphological data from field plants showed that transgenic plants performed better in field conditions. Incorporation of genes related to cotton fiber length and quality can provide new avenues for fiber improvement. The utilization of this technology would provide an efficient import substitution and sustained production of long-staple fiber in Pakistan to fulfill the industrial requirements.

Keywords: agrobacterium-mediated transformation, cotton fiber, sucrose synthase gene, staple length

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Authors: Elaine Stavro

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In our present world where acts of incivility, intolerance and anger towards minority communities is on the rise, the ways museum practices cultivate ethical generosity is of interest. Democratic theorists differ as to how they believe respect can be generated through active participation. Allowing minority communities a role in determining what artifacts will be displayed and how they will be displayed has been an important step in generating respect. In addition, the rise of indigenous museums, slave museums and curators who represent these communities, contribute to the communication of their history of oppression. These institutional practices have been supplemented by the handling of objects, recognition stories and multisensory exhibitions. Psychoanalysis, object relations theorists believe that the handling of objects: amenable objects and responsive listeners will trigger the expression of anomie, alienation and traumatizing experiences. Not only memorializing but engaging with one’s lose in a very personal way can facilitate the process of mourning. Manchester Museum (UK) gathered together Somalian refugees, who in the process of handling their own objects and those offered at the museum, began to tell their stories. Democratic theorists (especially affect theorists or vital materialists or Actor Network theorists) believe that things can be social actants- material objects have agentic capacities that humans should align with. In doing so, they challenge social constructivism that attributes power to interpreted things, but like them they assume an openness or responsiveness to Otherness can be cultivated. Rich sensory experiences, corporeal engagement (devices that involve bodily movement or objects that involve handling) auditory experiences (songs) all contribute to improve one’s responsiveness and openness to Others. This paper will focus specifically on slave museums/ and exhibits in the U.K, the USA., South Africa to explore and evaluate their democratic strategies in cultivating tolerant practices via the various democratic avenues outlined above.

Keywords: democratic pedagogy, slave exhibitions, affect/emotion, object handling

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Authors: Markus Feufel, Friederike Kendel, Caren Hilger, Selamawit Woldai

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Since the corona pandemic, the use of video consultation has increased remarkably. For vulnerable groups such as oncological patients, the advantages seem obvious. But how does video consultation potentially change the doctor-patient relationship compared to face-to-face consultation? Which barriers may hinder the effective use of this consultation format in practice? We are presenting first results from a mixed-methods field study, funded by Federal Ministry of Health, which will provide the basis for a hands-on guide for both physicians and patients on how to improve the quality of video consultations. We use a quasi-experimental design to analyze qualitative and quantitative differences between face-to-face and video consultations based on video recordings of N = 64 actual counseling sessions (n = 32 for each consultation format). Data will be recorded from n = 32 gynecological and n = 32 urological cancer patients at two clinics. After the consultation, all patients will be asked to fill out a questionnaire about their consultation experience. For quantitative analyses, the counseling sessions will be systematically compared in terms of verbal and nonverbal communication patterns. Relative frequencies of eye contact and the information exchanged will be compared using 𝝌2 -tests. The validated questionnaire MAPPIN'Obsdyad will be used to assess the expression of shared decision-making parameters. In addition, semi-structured interviews will be conducted with n = 10 physicians and n = 10 patients experienced with video consultation, for which a qualitative content analysis will be conducted. We will elaborate the comprehensive methodological approach we used to compare video vs. face-to-face consultations and present first evidence on how video consultations change the doctor-patient interaction. We will also outline possible barriers of video consultations and best practices on how they may be overcome. Based on the results, we will present and discuss recommendations outlining best practices for how to prepare and conduct high-quality video consultations from the perspective of both physicians and patients.

Keywords: video consultation, patient-doctor-relationship, digital applications, technical barriers

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Authors: Seyyed Mohammad Amin Mousavi Sagharchi, Elham Javanroudi

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Introduction: Tuberculosis (TB) is a known disease with hidden features caused by Mycobacterium tuberculosis (MTB). This disease, which is one of the 10 deadliest in the world, has caused millions of deaths in recent decades. Furthermore, TB is responsible for infecting about 30% population of world. Like any infection, TB can activate the immune system by locating and colonization in the human body, especially in the alveoli. TB is granulomatosis, so MTB can absorb the host’s immune cells and other cells to form granuloma. Method: Different databases (e.g., PubMed) were recruited to prepare this paper and fulfill our goals to search and find effective papers and investigations. Results: Immune response to MTB is related to T cell killers and contains CD1, CD4, and CD8 T lymphocytes. CD1 lymphocytes can recognize glycolipids, which highly exist in the Mycobacterial fatty cell wall. CD4 lymphocytes and macrophages form granuloma, and it is the main line of immune response to Mycobacteria. On the other hand, CD8 cells have cytolytic function for directly killing MTB by secretion of granulysin. Other functions and secretion to the deal are interleukin-12 (IL-12) by induction of expression interferon-γ (INF-γ) for macrophages activation and creating a granuloma, and tumor necrosis factor (TNF) by promoting macrophage phagolysosomal fusion. Conclusion: Immune cells in battle with MTB are macrophages, dendritic cells (DCs), neutrophils, and natural killer (NK) cells. These immune cells can recognize the Mycobacterium by various receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLRs), and C-type lectin receptors (CLRs) located in the cell surface. In human alveoli exist about 50 dendritic macrophages, which have close communication with other immune cells in the circulating system and epithelial cells to deal with Mycobacteria. Against immune cells, MTB handles some factors (e.g., cordfactor, O-Ag, lipoarabinomannan, sulfatides, and adenylate cyclase) and practical functions (e.g., inhibition of macrophages).

Keywords: mycobacterium tuberculosis, immune responses, immunological mechanisms, respiratory tuberculosis

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Authors: Leticia Leandro Rade, Amanda Silva de Sousa, Suman Das, Wesley Generoso, Mayara Chagas Ávila, Plinio Salmazo Vieira, Antonio Bonomi, Gabriela Persinoti, Mario Tyago Murakami, Thomas Michael Makris, Leticia Maria Zanphorlin

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Alkenes have an economic appeal, especially in the biofuels field, since they are precursors for drop-in biofuels production, which have similar chemical and physical properties to the conventional fossil fuels, with no oxygen in their composition. After the discovery of the first P450 CYP152 OleTJE in 2011, reported with its unique property of decarboxylating fatty acids (FA), by using hydrogen peroxide as a cofactor and producing 1-alkenes as the main product, the scientific and technological interest in this family of enzymes vastly increased. In this context, the present work presents a new decarboxylase (OleTRN) with low similarity with OleTJE (32%), its biochemical characterization, and structure elucidation. As main results, OleTRN presented a high yield of expression and purity, optimum reaction conditions at 35 °C and pH from 6.5 to 8.0, and higher specificity for oleic acid. Besides that, structure-guided mutations were performed and according to the functional characterizations, it was observed that some mutations presented different specificity and chemoselectivity by varying the chain-length of FA substrates from 12 to 20 carbons. These results are extremely interesting from a biotechnological perspective as those characteristics could diversify the applications and contribute to designing better cytochrome P450 decarboxylases. Considering that peroxygenases have the potential activity of decarboxylating and hydroxylating fatty acids and that the elucidation of the intriguing mechanistic involved in the decarboxylation preferential from OleTJE is still a challenge, the elucidation of OleTRN structure and the functional characterizations of OleTRN and its mutants contribute to new information about CYP152. Besides that, the work also contributed to the discovery of a new decarboxylase with a different selectivity profile from OleTJE, which allows a wide range of applications.

Keywords: P450, decarboxylases, alkenes, biofuels

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Ada Yurman

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Using the case of Israeli Atomic Spy Mordechai Vanunu as an example, this study sought to examine social response to political deviance whereby social response can be mobilized in order to achieve social control. Mordechai Vanunu, a junior technician in the Dimona Atomic Research Center, played a normative role in the militaristic discourse while working in the “holy shrine” of the Israeli defense system for many years. At a certain stage, however, Vanunu decided to detach himself from this collective and launched an assault on this top-secret circle. Israeli society in general and the security establishment in particular found this attack intolerable and unforgivable. They presented Vanunu as a ticking time bomb, delegitimized him and portrayed him as “other”. In addition, Israeli enforcement authorities imposed myriad prohibitions and sanctions on Vanunu even after his release from prison – “as will be done to he who desecrates holiness.” Social response to Vanunu at the time of his capture and trial was studied by conducting a content analysis of six contemporary daily newspapers. The analysis focused on use of language and forms of expression. In contrast with traditional content analysis methodology, this study did not just look at frequency of expressions of ideas and terms in the text and covert content; rather, the text was analyzed as a structural whole, and included examination of style, tone and unusual use of imagery, and more, in order to uncover hidden messages within the text. The social response to this case was extraordinarily intense, not only because in this case of political deviance, involving espionage and treason, Vanunu’s actions comprised a real potential threat to the country, but also because of the threat his behavior posed to the symbolic universe of society. Therefore, the response to this instance of political deviance can be seen as being part of a mechanism of social control aiming to protect world view of society as a whole, as well as to punish the criminal.

Keywords: militarism, political deviance, social construction, social control

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Authors: Lubna Azmi, Ila Shukla, Shyam Sundar Gupta, Padam Kant, Ch. V. Rao

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Gastric ulcer is a major global health threat, and it is the leading cause of stomach cancer death worldwide. Helicobacter pylori bacteriumis the most important etiologic factor for gastric ulcer. This infection is highly pervasive in South Asian developing countries, especially in India, Nepal, Srilanka etc. due to diversification in geographic area. Pathophysiology of gastric mucosal damage associated with non-invasive bacterium has not justified in detail, but it leads to change in histopathology, immunochemistry of the gastric and duodenal reason of host. The mechanism responsible for bacteria tissue tropism and mucosal damage in stomach variance during the disease is not clearly described and understood scientifically in treatment and control of pathogenic organisms. Polyphenols are secondary metabolites of plants and are generally involved in defense against aggression by pathogens. 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one and 1-hydroxy-5,7-dimethoxy-2-naphthalene-carboxaldehyde are polyphenolic compound obtained from popular Indian medicinal plants ghavpatta (ArgeriaspeciosaLinn.f) andBael (Aeglemarmelos) have long been used in traditional Ayurvedic Indian medicine for various diseases. They have promising effects on ulcer, as detailed investigation has made in our laboratory. Therefore, the aim of present study is to explore membrane –dependent morphogenesis of H. pylori and associated apoptosis-mediated cell death. Based on this we analyzed immune gene expression in stomach of experimental animals with H. pylori, using quantitative reverse transcription polymerase chain reaction(q RT-PCR). This revealed rapid induction of prostaglandin, interferon I (INF-I), interferon II (INF-II) and INF-I associated genes in the infected animal. Ultrastructural changes associated with H. pylori will be taken for advanced studies. This investigation shows that the biomarkers eradicate H. pylori bacterium caused gastric ulcer which is a major risk factor for gastric cancer.

Keywords: gastric ulcer, Helicobacter pylori, immunochemistry, polyphenols

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Authors: Hyeon Sop Baek

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This paper will briefly investigate Jeong Do-jeon’s political philosophy. Jeong Do-jeon was a Korean Confucian philosopher and politician during the turbulent 14th Century who revolted against the old order, founded Joseon Dynasty, and significantly impacted the development of Korean culture. Jeong’s vision of an ideal state involved a polity that has its roots in the people -that is, an ideal government prioritizes caring for the welfare of the people, respecting and attending to the diverse opinions and concerns of the people, and relies on the genuine, voluntary support of the people. With the neo-Confucian worldview in mind -that every human being has the equal potential to become a moral person- Jeong sought to create a world suitable for everybody to contribute to the decision-making procedure and be able to realize their potential fully. This paper will first examine his works and present a quick overview of his vision of the ideal government. Then, it will examine the Confucian virtues of ren (仁) and yi (義) and how they formulate the basis of his philosophy, and then discuss the central features of his vision of government: popular mandate, equity of wealth, promoting freedom of expression and political participation, and elevating caring disposition as the paramount quality of the political leaders. Furthermore, this paper aims to analyze the element of care inherent within his political philosophy, namely his view on the dynamics of power, nurturing the people, and noncoercive justice. Finally, a discussion on why his philosophy is still relevant in the contemporary context will be provided. Jeong’s view aimed at building a sustainable model of government, by proposing that the people should be the foundation of a state and that they need to be carefully nurtured so they can realize their inborn potential and continue to contribute to the sustenance of the world, is the focal point of Jeong’s philosophy. Just as he sought to rebuild his world following the turmoils of the 14th Century, his philosophy still has a substantial implication on how we should strive to rebuild our society today.

Keywords: Korea, Confucianism, Jeong Do-jeon, Joseon, Korean philosophy, political philosophy

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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