Search results for: genes expression

Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

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Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Neha Toppo

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Method and strategies of teaching instruction highly influence learning of students. In second language teaching, number of ways and methods has been suggested by different scholars and researchers through times. The present article deals with the role of teaching instruction in developing compositional ability of students in writing. It focuses on the secondary level students of rural areas, whose exposure to English language is limited and they face challenges even in simple compositions. The students till high school suffer with their disability in writing formal letter, application, essay, paragraph etc. They face problem in note making, writing answers in examination using their own words and depend fully on rote learning. It becomes difficult for them to give language to their own ideas. Teaching writing composition deserves special attention as writing is an integral part of language learning and students at this level are expected to have sound compositional ability for it is useful in numerous domains. Effective method of instruction could help students to learn expression of self, correct selection of vocabulary and grammar, contextual writing, composition of formal and informal writing. It is not limited to school but continues to be important in various other fields outside the school such as in newspaper and magazine, official work, legislative work, material writing, academic writing, personal writing, etc. The study is based on the experimental method, which hypothesize that guided instruction will be more effective in teaching writing compositions than usual instruction in which students are left to compose by their own without any help. In the test, students of one section are asked to write an essay on the given topic without guidance and another section are asked to write the same but with the assistance of guided instruction in which students have been provided with a few vocabulary and sentence structure. This process is repeated in few more schools to get generalize data. The study shows the difference on students’ performance using both the instructions; guided and unguided. The conclusion of the study is followed by the finding that writing skill of the students is quite poor but with the help of guided instruction they perform better. The students are in need of better teaching instruction to develop their writing skills.

Keywords: composition, essay, guided instruction, writing skill

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Authors: Bruna Lima Gomes, Vanessa Caroline De Barros Bonato, Luciano Freschi, Eduardo Purgatto

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Plant hormones are long known to be tightly associated with fruit development and are involved in controlling various aspects of fruit ripening. For fleshy fruits, ripening is characterized for changes in texture, color, aroma and other parameters that markedly contribute to its quality. Ethylene is one of the major players regulating the ripening-related processes, but emerging evidences suggest that auxin is also part of this dynamic control. Thus, the aim of this study was providing new insights into the auxin role during ripening and the hormonal interplay between auxin and ethylene. For that, tomato fruits (Micro-Tom) were collected at mature green stage and separated in four groups: one for indole-3-acetic acid (IAA) treatment, one for ethylene, one for a combination of IAA and ethylene, and one for control. Hormone solution was injected through the stylar apex, while mock samples were injected with buffer only. For ethylene treatments, fruits were exposed to gaseous hormone. Then, fruits were left to ripen under standard conditions and to assess ripening development, hue angle was reported as color indicator and ethylene production was measured by gas chromatography. The transcript levels of three ripening-related ethylene receptors (LeETR3, LeETR4 and LeETR6) were evaluated by RT-qPCR. Results showed that ethylene treatment induced ripening, stimulated ethylene production, accelerated color changes and induced receptor expression, as expected. Nonetheless, auxin treatment showed the opposite effect once fruits remained green for longer time than control group and ethylene perception has changed, taking account the reduced levels of receptor transcripts. Further, treatment with both hormones revealed that auxin effect in delaying ripening was predominant, even with higher levels of ethylene. Altogether, the data suggest that auxin modulates several aspects of the tomato fruit ripening modifying the ethylene perception. The knowledge about hormonal control of fruit development will help design new strategies for effective manipulation of ripening regarding fruit quality and brings a new level of complexity on fruit ripening regulation.

Keywords: ethylene, auxin, fruit ripening, hormonal crosstalk

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Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

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Authors: Omnia Elkommos

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Language is communication on several discourse levels. The target of teaching a language and the literature of a foreign language is to communicate a message. Reading, appreciating, analysing, and interpreting poetry as a sophisticated rhetorical expression of human thoughts, emotions, and philosophical messages is more feasible through the use of linguistic pragmatic tools from a communicative discourse perspective. The poet's intention, speech act, illocutionary act, and perlocutionary goal can be better understood when communicative situational context as well as linguistic discourse structure theories are employed. The use of linguistic theories in the teaching of poetry is, therefore, intrinsic to students' comprehension, interpretation, and appreciation of poetry of the different ages. It is the purpose of this study to show how both teachers as well as students can apply these linguistic theories and tools to dramatic poetic texts for an engaging, enlightening, and effective interpretation and appreciation of the language. Theories drawn from areas of pragmatics, discourse analysis, embedded discourse level, communicative situational context, and other linguistic approaches were applied to selected poetry texts from the different centuries. Further, in a simple statistical count of the number of poems with dialogic dramatic discourse with embedded two or three levels of discourse in different anthologies outweighs the number of descriptive poems with a one level of discourse, between the poet and the reader. Poetry is thus discourse on one, two, or three levels. It is, therefore, recommended that teachers and students in the area of ESL/EFL use the linguistics theories for a better understanding of poetry as communicative discourse. The practice of applying these linguistic theories in classrooms and in research will allow them to perceive the language and its linguistic, social, and cultural aspect. Texts will become live illocutionary acts with a perlocutionary acts goal rather than mere literary texts in anthologies.

Keywords: coda, commissives, communicative situation, context of culture, context of reference, context of utterance, dialogue, directives, discourse analysis, dramatic discourse interaction, duologue, embedded discourse levels, language for communication, linguistic structures, literary texts, poetry, pragmatic theories, reader response, speech acts (macro/micro), stylistics, teaching literature, TEFL, terms of address, turn-taking

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Authors: N. Manjunatha, K. T. Rangswamy, N. Nagaraju, H. A. Prameela, P. Rudraswamy, M. Krishnareddy

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The identification of virus in cowpea especially potyviruses is confusing. Even though there are several studies on viruses causing diseases in cowpea, difficult to distinguish based on symptoms and serological detection. The differentiation of potyviruses considering as a constraint, the present study is initiated for molecular characterization, host plant resistance and epidemiology of the BCMV infecting cowpea. The etiological agent causing cowpea mosaic was identified as Bean Common Mosaic Virus (BCMV) on the basis of RT-PCR and electron microscopy. An approximately 750bp PCR product corresponding to coat protein (CP) region of the virus and the presence of long flexuous filamentous particles measuring about 952 nm in size typical to genus potyvirus were observed under electron microscope. The characterized virus isolate genome had 10054 nucleotides, excluding the 3’ terminal poly (A) tail. Comparison of polyprotein of the virus with other potyviruses showed similar genome organization with 9 cleavage sites resulted in 10 functional proteins. The pairwise sequence comparison of individual genes, P1 showed most divergent, but CP gene was less divergent at nucleotide and amino acid level. A phylogenetic tree constructed based on multiple sequence alignments of the polyprotein nucleotide and amino acid sequences of cowpea BCMV and potyviruses showed virus is closely related to BCMV-HB. Whereas, Soybean variant of china (KJ807806) and NL1 isolate (AY112735) showed 93.8 % (5’UTR) and 94.9 % (3’UTR) homology respectively with other BCMV isolates. This virus transmitted to different leguminous plant species and produced systemic symptoms under greenhouse conditions. Out of 100 cowpea genotypes screened, three genotypes viz., IC 8966, V 5 and IC 202806 showed immune reaction in both field and greenhouse conditions. Single marker analysis (SMA) was revealed out of 4 SSR markers linked to BCMV resistance, M135 marker explains 28.2 % of phenotypic variation (R2) and Polymorphic information content (PIC) value of these markers was ranged from 0.23 to 0.37. The correlation and regression analysis showed rainfall, and minimum temperature had significant negative impact and strong relationship with aphid population, whereas weak correlation was observed with disease incidence. Path coefficient analysis revealed most of the weather parameters exerted their indirect contributions to the aphid population and disease incidence except minimum temperature. This study helps to identify specific gaps in knowledge for researchers who may wish to further analyse the science behind complex interactions between vector-virus and host in relation to the environment. The resistant genotypes identified are could be effectively used in resistance breeding programme.

Keywords: cowpea, epidemiology, genotypes, virus

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Authors: Benjamin Glasner, Carlos Henriquez, Fernando Alfaro, Nicole Trefault, Santiago Andrade, Rodrigo De La Iglesia

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A central question in ecology refers to the relative importance that local-scale variables have over community composition, when compared with regional-scale variables. In coastal environments, strong seasonal abiotic influence dominates these systems, weakening the impact of other parameters like micronutrients. After the industrial revolution, micronutrients like trace metals have increased in ocean as pollutants, with strong effects upon biotic entities and biological processes in coastal regions. Coastal picoplankton communities had been characterized as a cyanobacterial dominated fraction, but in recent years the eukaryotic component of this size fraction has gained relevance due to their high influence in carbon cycle, although, diversity patterns and responses to disturbances are poorly understood. South Pacific upwelling coastal environments represent an excellent model to study seasonal changes due to a strong influence in the availability of macro- and micronutrients between seasons. In addition, some well constrained coastal bays of this region have been subjected to strong disturbances due to trace metal inputs. In this study, we aim to compare the influence of seasonality and trace metals concentrations, on the community structure of planktonic picoeukaryotes. To describe seasonal patterns in the study area, satellite data in a 6 years time series and in-situ measurements with a traditional oceanographic approach such as CTDO equipment were performed. In addition, trace metal concentrations were analyzed trough ICP-MS analysis, for the same region. For biological data collection, field campaigns were performed in 2011-2012 and the picoplankton community was described by flow cytometry and taxonomical characterization with next-generation sequencing of ribosomal genes. The relation between the abiotic and biotic components was finally determined by multivariate statistical analysis. Our data show strong seasonal fluctuations in abiotic parameters such as photosynthetic active radiation and superficial sea temperature, with a clear differentiation of seasons. However, trace metal analysis allows identifying strong differentiation within the study area, dividing it into two zones based on trace metals concentration. Biological data indicate that there are no major changes in diversity but a significant fluctuation in evenness and community structure. These changes are related mainly with regional parameters, like temperature, but by analyzing the metal influence in picoplankton community structure, we identify a differential response of some plankton taxa to metal pollution. We propose that some picoeukaryotic plankton groups respond differentially to metal inputs, by changing their nutritional status and/or requirements under disturbances as a derived outcome of toxic effects and tolerance.

Keywords: Picoeukaryotes, plankton communities, trace metals, seasonal patterns

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Authors: K. Frahtia, I. Mihoubi, S. Picot

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Leishmaniasis is a group of parasitic disease with a varied clinical expression caused by flagellate protozoa of the Leishmania genus. These diseases are transmitted to humans and animals by the sting of a vector insect, the female sandfly. Among the groups of dipteral disease vectors, Phlebotominae occupy a prime position and play a significant role in human pathology, such as leishmaniasis that affects nearly 350 million people worldwide. The vector control operation launched by health services throughout the country proves to be effective since despite the prevalence of the disease remains high especially in rural areas, leishmaniasis appears to be declining in Algeria. In this context, this study mainly concerns molecular detection of Leishmania from the vector. Furthermore, a molecular diagnosis has also been made on skin samples taken from patients in the region of Constantine, located in the North-East of Algeria. Concerning the vector, 5858 sandflies were captured, including 4360 males and 1498 females. Male specimens were identified based on their morphological. The morphological identification highlighted the presence of the Phlebotomus genus with a prevalence of 93% against 7% represented by the Sergentomyia genus. About the identified species, P. perniciosus is the most abundant with 59.4% of the male identified population followed by P. longicuspis with 24.7% of the workforce. P. perfiliewi is poorly represented by 6.7% of specimens followed by P. papatasi with 2.2% and 1.5% S. dreyfussi. Concerning skin samples, 45/79 (56.96%) collected samples were found positive by real-time PCR. This rate appears to be in sharp decline compared to previous years (alert peak of 30,227 cases in 2005). Concerning the detection of Leishmania from sandflies by RT-PCR, the results show that 3/60 PCR performed genus are positive with melting temperatures corresponding to that of the reference strain (84.1 +/- 0.4 ° C for L. infantum). This proves that the vectors were parasitized. On the other side, identification by RT-PCR species did not give any results. This could be explained by the presence of an insufficient amount of leishmanian DNA in the vector, and therefore support the hypothesis of the regression of leishmaniasis in Constantine.

Keywords: Algeria, molecular diagnostic, phlebotomus, real time PCR

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Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

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A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

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Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

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Authors: Natsuko D'Aprile

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The construction of Nation-States is a historical process that produces a type of national identity and culture that States nowadays mobilise for global outreach. National culture, as a set of norms and values influencing individuals’ actions and decisions, produces a type of policy making of various strategies that impact how a Nation is promoted overseas. The 1990s were marked by a resurgence of the debates on national identity. This period is believed to have paved the way for nationalism and witnessed increased attention to analytical approaches to identity. Public diplomacy is a concrete example of how national culture is mobilised to project a favourable image of a Nation abroad, especially in the narratives on national identity mobilised by diplomatic actors. Public diplomacy is understood as providing tools for States to build and project strategic narratives that represent events and identities in an attempt to influence domestic and foreign audiences, be they domestic or foreign. France and Japan received little attention on the matter. This research hence aims to investigate how France and Japan have mobilised narratives on national identity since the 1990s in the context of their public diplomacy. To understand how identities are framed, qualitative and quantitative discourse analysis has been performed on a corpus of various speeches held by French and Japanese political actors in which they present their diplomacy goals, as well as official documents provided by both Ministries of Foreign Affairs. This analysis showed that the French discourse integrates a narrative on France’s universal vocation, relying on the expression of a Nation whose model is worldly applicable and has the legitimacy to influence international decisions. The Japanese discourse does not concretely emphasise Japanese or Asian values, except for some narratives integrating Confucian and Shintō values. It rather revolves around the need for Japan to ensure its citizens’ security and prosperity, hence the need for the Government to contribute to peace in the Asia-Pacific region and the world.

Keywords: comparative politics, culture, discourse analysis, narratives, public diplomacy

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Authors: Nazia Shehzad

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Language and art can supplement and correlate each other. Through the ages art has been a means of visual expression used to convey a wide series of incarnated ideas. Art can take the perceiver into different times and into different worlds. It can also be used to introduce different levels of vocabulary to the learners of a second language. Learning a second language for most students is a very difficult and strenuous experience. They are not only trying to accommodate to a new language but are also trying to adjust to themselves and a new environment. They are anxious about almost everything, but they are especially self-conscious about their performance in the classroom. By relocating the focus from the student to an object, everyone participates, thus waiving a certain degree of self-consciousness. The experience, a student has with art in the classroom has to be gratifying for both the student and the teacher. If the atmosphere in the classroom is too grave it will not serve any useful purpose. Art is an excellent way to teach English and encourage collaboration and interaction between students of all ages. As making art involves many different processes, it is wonderful for classification and following/giving instructions. It is also an effective way to achieve and implement language of characterization and comparison and vocabulary acquirement for the elements of design (shape, size, color, texture, tone etc.) is so much more entertaining if done in a practical and hands-on way. Expressing ideas and feelings through art is also of immeasurable value where students are at the beginning stages of English language acquisition and for many of my Saudi students it was a form of therapy. It is also a way to respect, search, examine and share the cultural traditions of different cultures, and of the students themselves. Art not only provides a field for ideas to keep aimless, meandering minds of students' busy but is also a productive tool to analyze English language in a new order. As an ESL teacher, using art is a highly compelling way to bridge the gap between student and teacher. It’s difficult to keep students concentrated, especially when they speak a different language. To get students to actually learn and explore something in your foreign language lesson, artwork is your best friend. Many teachers feel that through amalgamation of the arts into their academic lessons students are able to learn more profoundly because they use diverse ways of thinking and problem solving. Teachers observe that drawing often retains students who might otherwise be dispassionate and can help students move ahead simple recall when they are asked to make connections and come up with an exclusive interpretation through an artwork or drawing. Students use observation skills when they are drawing, and this can help to persuade students who might otherwise remain silent or need more time to process information.

Keywords: amalgamation of arts, expressing ideas and feelings through arts, effective way to achieve and implement language, language and art can supplement and correlate each other

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Authors: Mei-Ling Chan, Jin-Ming Wu, Konstantin V. Kudryavtsev, Jih-Hwa Guh

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Prostate cancer is one of the most common malignant disease in men. KUD983 is an enantiomerically pure β-dipeptide derivative, which may have anti-cancer effects. In the present study, KUD983 exhibits powerful activity against hormone-refractory prostate cancer (HRPC) PC-3 and DU145 cells. The IC50 values of KUD983 in PC-3 and DU145 cells are 0.56±0.07M and 0.50±0.04 M respectively. KUD983 induced G1 arrest of the cell cycle and subsequent apoptosis associated with the down-regulation of several related proteins including cyclin D1, cyclin E and Cdk4, and the de-phosphorylation of RB. The protein expressions of nuclear and total c-Myc protein, which was able to regulate the expression of both cyclin D1 and cyclin E, were significantly suppressed by KUD983. Phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is an important signaling pathway that influences the energy metabolism, cell cycle, proliferation, survival and apoptosis of cells, and is associated with numerous other signaling pathways. The Western Blot data revealed that KUD983 inhibited PI3K/Akt and mTOR/p70S6K/4E-BP1 pathways. The transient transfection of constitutively active myristylated Akt (myr-Akt) cDNA significantly reversed KUD983-induced caspase activation but did not abolish the suppression of mTOR/p70S6K/4E-BP1 signaling cascade indicating the presence of both Akt-dependent and -independent pathways. Moreover, KUD983-induced effect was collaborated with the down-regulation of anti-apoptotic Bcl-2 members (e.g., Bcl-2, and Mcl-1) and IAP family members (e.g., survivin). Furthermore, KUD983 induced autophagic cell death using confocal microscopic examination, investigating the level of conversion of LC3-I to LC3-II and flow cytometric detection of AVO-positive cells. Taken together, the data suggest that KUD983 is an anticancer β-dipeptide against HRPCs through the inhibition of cell proliferation and induction of apoptotic and autophagic cell death. The suppression of signaling pathways mediated by c-Myc, PI3K/Akt and mTOR/p70S6K/4E-BP1 and the collaboration with down-regulation of Mcl-1 and survivin may indicate the mechanism of KUD983 against HRPC.

Keywords: β-dipeptide, hormone-refractory prostate cancer, mTOR, PI3K/Akt

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Authors: Emma Castiglioni, Nigel Scrutton, Derren Heyes, Alistair Fielding

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By using light as trigger, it is possible to study many biological processes, such as the activity of genes, proteins, and other molecules, with precise spatiotemporal control. Caged compounds, where biologically active molecules are generated from an inert precursor upon laser photolysis, offer the potential to initiate such biological reactions with high temporal resolution. As light acts as the trigger for cleaving the protecting group, the ‘caging’ technique provides a number of advantages as it can be intracellular, rapid and controlled in a quantitative manner. We are developing caging strategies to study the catalytic cycle of a number of enzyme systems, such as nitric oxide synthase and ethanolamine ammonia lyase. These include the use of caged substrates, caged electrons and the possibility of caging the enzyme itself. In addition, we are developing a novel freeze-quench instrument to study these reactions, which combines rapid mixing and flashing capabilities. Reaction intermediates will be trapped at low temperatures and will be analysed by using electron paramagnetic resonance (EPR) spectroscopy to identify the involvement of any radical species during catalysis. EPR techniques typically require relatively long measurement times and very often, low temperatures to fully characterise these short-lived species. Therefore, common rapid mixing techniques, such as stopped-flow or quench-flow are not directly suitable. However, the combination of rapid freeze-quench (RFQ) followed by EPR analysis provides the ideal approach to kinetically trap and spectroscopically characterise these transient radical species. In a typical RFQ experiment, two reagent solutions are delivered to the mixer via two syringes driven by a pneumatic actuator or stepper motor. The new mixed solution is then sprayed into a cryogenic liquid or surface, and the frozen sample is then collected and packed into an EPR tube for analysis. The earliest RFQ instrument consisted of a hydraulic ram unit as a drive unit with direct spraying of the sample into a cryogenic liquid (nitrogen, isopentane or petroleum). Improvements to the RFQ technique have arisen from the design of new mixers in order to reduce both the volume and the mixing time. In addition, the cryogenic isopentane bath has been coupled to a filtering system or replaced by spraying the solution onto a surface that is frozen via thermal conductivity with a cryogenic liquid. In our work, we are developing a novel RFQ instrument which combines the freeze-quench technology with flashing capabilities to enable the studies of both thermally-activated and light-activated biological reactions. This instrument also uses a new rotating plate design based on magnetic couplings and removes the need for mechanical motorised rotation, which can otherwise be problematic at cryogenic temperatures.

Keywords: caged compounds, freeze-quench apparatus, photolysis, radicals

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Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

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Authors: Sujit Kumar

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Historicity of inter-caste relations can be traced in the early stages of evolution of rural community in the Indian society. These have witnessed vicissitudes during long drawn interactions between caste groups. Inter-caste relations evolved in a more organized form in the guise of Jajmani system. This is a system of permanent and hereditary inter-caste relations and gives a kaleidoscopic view of socio-economic relations among various caste groupings. Universality of its prevalence in rural India for centuries is well recognized and documented. But it has been undergoing metamorphic change in some regions and changing at a slower pace in the others during post-independence period. An empirical study was conducted with the objectives to know whether Jajmani system is in vogue in the rural areas and type and intensity of socio-economic ties among different caste categories and to find out the change in inter-caste relations, if any owing to industrialization and modernization. Information was elicited from 225 respondents using interview schedule designed for this purpose. It is discernible that in majority of cases, inter-caste social relations which find better expression on the occasions like marriage, death, birth and festivals etc. among Brahmins and lower castes vis-à-vis other caste categories have grown weak. The data further unearth that economic relations as maintained on the occasions of marriage, sacred thread ceremony, mundan sacrament, birthday, death, yajna, katha, routine hair cut, manufacture and repair of various iron, earthen, wooden and leather articles between members of higher castes (general category) and lower castes (scheduled castes) are moderate but weak in case of Other Backward Classes vis-à-vis all other caste categories. Overwhelming majority of informants believe that decline in hereditary occupations, depreciation of old products and services and their availability from the market being made by industry are main reasons in descending order for change in inter caste relations. Modernization, westernization, industrialization, transportation and communications, growing materialism and consumerism together have brought change in relations among caste groups affecting about a billion population inhabiting rural India.

Keywords: inter-caste, Jajmani, sacrament, Yajna

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Authors: Zahra Mohajer, Afsaneh Soltani

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Doping is a major issue in competitive sports and is favored by vast groups of athletes. The feeling of being higher-ranking than others and gaining fame has caused many athletes to misuse drugs. The definition of doping is to use prohibited substances and/or methods that help physical or mental performances or both. Doping counts as the illegal use of chemical substances or drugs, excessive amounts of physiological substances to increase the performance at or out of competition or even the use of inappropriate medications to treat an injury to gain the ability to participate in a competition. The International Olympic Committee (IOC) and World Anti-Doping Agency (WADA) have forbidden these substances to ensure fair and equal competition and also the health of the competitors. As of 2004 WADA has published an international list of illegal substances used for doping, which is updated annually. In the process of the Genome Project scientists have gained the ability to treat numerous diseases by gene therapy, which may result in bodily performance increase and therefore a potential opportunity to misuse by some athletes. Gene doping is defined as the non-therapeutic direct and indirect genetic modifications using genetic materials that can improve the performances in sports events. Biosynthetic drugs are a form of indirect genetic engineering. The method can be performed in three ways such as injecting the DNA directly into the muscle, inserting the genetically engineered cells, or transferring the DNA using a virus as a vector. Erythropoietin is a hormone majorly released by the kidney and in small amounts by the liver. Its function is to stimulate the erythropoiesis and therefore the more production of red blood cells (RBC) which causes an increase in Hemoglobin (Hb). During this process, the oxygen delivery to muscles will increase, which will improve athletic performance and postpone exhaustion. There are ways to increase the oxygen transferred to muscles such as blood transfusion, stimulating the production of red blood cells by using Erythropoietin (EPO), and also using allosteric effectors of Hemoglobin. EPO can either be injected as a protein or can be inserted into the cells as the gene which encodes EPO. Adeno-associated viruses have been employed to deliver the EPO gene to the cells. Employing the genes that naturally exist in the human body such as the EPO gene can reduce the risk of detecting gene doping. The first research about blood doping was conducted in 1947. The study has shown that an increase in hematocrit (HCT) up to 55% following homologous transfusion makes it more unchallenging for the body to perform the exercise at the altitude. Thereafter athletes’ attraction to blood infusion escalated. Also, a study has demonstrated that by reinfusing their own blood 4 weeks after being drawn, three men have shown a rise in Hb level which improved the oxygen uptake, and a delay in exhaustion. The list of performance-enhancing drugs is published by WADA annually and includes the following drugs: anabolic agents, hormones, Beta-2 agonists, Beta-blockers, Diuretics, Stimulants, narcotics, cannabinoids, and corticosteroids.

Keywords: doping, PEDs, sports, WADA

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Authors: Dong-An Wang

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All kinds of microspheres have been extensively employed as carriers for drug, gene and therapeutic cell delivery. Most therapeutic cell delivery microspheres rely on a two-step methodology: fabrication of microspheres and subsequent seeding of cells onto them. In this study, we have developed a novel one-step cell encapsulation technique using a convenient and instant water-in-oil single emulsion approach to form cell-encapsulated gelatin microspheres. This technology is adopted for hyaline cartilage tissue engineering, in which autologous chondrocytes are used as therapeutic cells. Cell viability was maintained throughout and after the microsphere formation (75-100 µm diameters) process that avoids involvement of any covalent bonding reactions or exposure to any further chemicals. Further encapsulation of cell-laden microspheres in alginate gels were performed under 4°C via a prompt process. Upon the formation of alginate constructs, they were immediately relocated into CO2 incubator where the temperature was maintained at 37°C; under this temperature, the cell-laden gelatin microspheres dissolved within hours to yield similarly sized cavities and the chondrocytes were therefore suspended within the cavities inside the alginate gel bulk. Hence, the gelatin cell-laden microspheres served two roles: as cell delivery vehicles which can be removable through temperature curing, and as porogens within an alginate hydrogel construct to provide living space for cell growth and tissue development as well as better permeability for mutual diffusions. These cell-laden microspheres, namely “temperature-cured dissolvable gelatin microsphere based cell carriers” (tDGMCs), were further encapsulated in a chondrocyte-laden alginate scaffold system and analyzed by WST-1, gene expression analyses, biochemical assays, histology and immunochemistry stains. The positive results consistently demonstrated the promise of tDGMC technology in delivering these non-anchorage dependent cells (chondrocytes). It can be further conveniently translated into delivery of other non-anchorage dependent cell species, including stem cells, progenitors or iPS cells, for regeneration of tissues in internal organs, such as engineered hepatogenesis or pancreatic regeneration.

Keywords: biomaterials, tissue engineering, microsphere, hydrogel, porogen, anchorage dependence

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Authors: Bahor Bahriddinovna Turaeva

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The article provides a structural analysis of the titles of the famous Kyrgyz writer Chingiz Aitmatov’s creative works “The Day Lasts More Than a Hundred Years”, “Doomsday”. The author’s creative purpose in naming the work of art, the role of the elements of the plot, and the composition of the novels in revealing the essence of the title are explained. The criteria that are important in naming the author’s works in different genres are classified, and the titles that mean artistic time and artistic space are studied separately. Chronotope is being concerned as the literary-aesthetic category in world literary studies, expressing the scope of the universe interpretation, the author’s outlook and imagination regarding the world foundation, defining personages, and the composition means of expressing the sequence and duration of the events. A creative comprehension of the chronotope as a means of arranging the work composition, structure and constructing an epic field of the text demands a special approach to understanding the aesthetic character of the work. Since the chronotope includes all the elements of a fictional work, it is impossible to present the plot, composition, conflict, system of characters, feelings, and mood of the characters without the description of the chronotope. In the following development of the scientific-theoretical thought in the world, the chronotope is accepted to be one of the poetic means to demonstrate reality as well as to be a literary process that is basic for the expression of reality in the compositional construction and illustration of the plot relying on the writer’s intention and the ideological conception of the literary work. Literary time enables one to cognate the literary world picture created by the author in terms of the descriptive subject and object of the work. Therefore, one of the topical tasks of modern Uzbek literary studies is to describe historical evidence, event, the life of outstanding people, the chronology of the near past based on the literary time; on the example of the creative works of a certain period, creators or an individual writer are analyzed in separate or comparative-typological aspect.

Keywords: novel, title, chronotope, motive, epigraph, analepsis, structural analysis, plot line, composition

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Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

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Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Narayan Moger, Divya B., Preethi Jambagi, Krishnaveni C. K., Apsana M. R., B. R. Patil, Basvaraj Bagewadi

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Salinity is one of the major threats to world food security. Considering the requirement for salt tolerant crop plants in the present study was undertaken to clone and transferred the salt tolerant ectA gene from marine ecosystem into agriculture crop system to impart salinity tolerance. Ectoine is the compatible solute which accumulates in the cell membrane, is known to be involved in salt tolerance activity in most of the Halophiles. The present situation is insisting to development of salt tolerant transgenic lines to combat abiotic stress. In this background, the investigation was conducted to develop transgenic tomato lines by cloning and transferring of ectA gene is an ectoine derivative capable of enzymatic action for the production of acetyl-diaminobutyric acid. The gene ectA is involved in maintaining the osmotic balance of plants. The PCR amplified ectA gene (579bp) was cloned into T/A cloning vector (pTZ57R/T). The construct pDBJ26 containing ectA gene was sequenced by using gene specific forward and reverse primers. Sequence was analyzed using BLAST algorithm to check similarity of ectA gene with other isolates. Highest homology of 99.66 per cent was found with ectA gene sequences of isolates Halomonas elongata with the available sequence information in NCBI database. The ectA gene was further sub cloned into pRI101-AN plant expression vector and transferred into E. coli DH5α for its maintenance. Further pDNM27 was mobilized into A. tumefaciens LBA4404 through tri-parental mating system. The recombinant Agrobacterium containing pDNM27 was transferred into tomato plants through In planta plant transformation method. Out of 300 seedlings, co-cultivated only twenty-seven plants were able to well establish under the greenhouse condition. Among twenty-seven transformants only twelve plants showed amplification with gene specific primers. Further work must be extended to evaluate the transformants at T1 and T2 generations for ectoine accumulation, salinity tolerance, plant growth and development and yield.

Keywords: salinity, computable solutes, ectA, transgenic, in planta transformation

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Authors: Manuela Amorim, Cláudia S. Marques, Maria Conceição Calhau, Hélder J. Pinheiro, Maria Manuela Pintado

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Recently it has been recognized peptides from different food sources with biological activities. However, no relevant study has proven the potential of brewer yeast peptides in the modulation of gut microbiota. The importance of human intestinal microbiota in maintaining host health is well known. Probiotics, prebiotics and the combination of these two components, can contribute to support an adequate balance of the bacterial population in the human large intestine. The survival of many bacterial species inhabiting the large bowel depends essentially on the substrates made available to them, most of which come directly from the diet. Some of these substrates can be selectively considered as prebiotics, which are food ingredients that can stimulate beneficial bacteria such as Lactobacilli or Bifidobacteria growth in the colon. Moreover, conventional food can be used as vehicle to intake bioactive compounds that provide those health benefits and increase people well-being. In this way, the main objective of this work was to study the potential prebiotic activity of brewer yeast peptide extract (BYP) obtained via hydrolysis of yeast proteins by cardosins present in Cynara cardunculus extract for possible use as a functional ingredient. To evaluate the effect of BYP on the modulation of gut microbiota in diet-induced obesity model, Wistar rats were fed either with a standard or a high-fat diet. Quantified via 16S ribosomal RNA (rRNA) expression by quantitative PCR (qPCR), genera of beneficial bacteria (Lactobacillus spp. and Bifidobacterium spp.) and three main phyla (Firmicutes, Bacteroidetes and Actinobacteria) were assessed. Results showed relative abundance of Lactobacillus spp., Bifidobacterium spp. and Bacteroidetes was significantly increased (P < 0.05) by BYP. Consequently, the potential health-promoting effects of WPE through modulation of gut microbiota were demonstrated in vivo. Altogether, these findings highlight the possible intervention of BYP as gut microbiota enhancer, promoting healthy life style, and the incorporation in new food products, leads them bringing associated benefits endorsing a new trend in the improvement of new value-added food products.

Keywords: functional ingredients, gut microbiota, prebiotics, brewer yeast peptide extract

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Authors: Eunyup Yeom

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The roles of male and female in context of cuisine have developed into stereotypes throughout history. However¬— with Korea’s fast advancement in politics, technology, society and social standards¬— gender stereotypes have become blurred. This is not to say that such stereotypes no longer exist for they still remain present in media and advertisements embedding ‘idealistic’ ideas into the unconscious state of minds of viewers. Many media outlets, especially commercials, portray males expressing pleasure of food [that they are advertising] through audible qualities generally considered ‘rude’ and ‘unmannered’ in the Korean society. Females, on the other hand, express such pleasures only verbally. This happenstance of a stereotype is displayed bluntly in instant noodle, namely ramen, commercials. This research explores the cultural significance of a type of audible gesture that can be found in Korean speech in which is termed the Fricative Voice Gesture (FVG). There are two forms of FVGs: the reactive and the prosodic. The reactive FVG is a legitimate form of expression while the prosodic FVG works as a speech intensifier. So, in order to understand this stereotype of who is authorized to express sensorial pleasure as a reactive FVG as opposed to a prosodic FVG, information has been extracted from interviews and dissected numerous ramen/instant noodle commercials and its appearances in other mediums of media. The commercials were tediously analyzed in all aspects of dialogue, featured contents, background music, actors and/or actresses selling the product, body language, and voice gestures. To effectively understand the exact impact these commercials have on the audience, each commercial was viewed with an interviewee. In this research, there were main informants whom were all Korean students residing in South Korea. All three interviewees were able to attend interview and commercial viewing sessions via Skype. This research, overall, focuses and concludes on Harkness’s statement of how the reactive FVG is a recognizable index of the privileging of males for Korean culture norms and, in parallel, food commercials are still conforming to male ideals and fantasies.

Keywords: advertisement, food politics, fricative voice gestures, gender politics

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Abenezer Nigussie

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Strategic control practice is a critical exercise, as it provides a sturdy influence towards firms or production partners to achieve the full implementation of effective predetermined plans. The importance of strategic control in a company is often measured by observing the relationship between strategic management and organizational performance. The conventional philosophy of strategic control in academia and the industry places significant emphasis on the ability to plan and execute initiatives. In contrast, the same emphasis on strategic management has received less attention in the housing industry. Although the pressures of project performance can often obscure the wider social, economic, and professional context in which strategic management is undertaken, it is these broad contextual areas that make strategic control a vital issue for construction businesses. Rapidly changing social and technological issues are creating an informed environment that will appear very different in the coming decades from what is experienced in today’s companies. Construction project activity is not adequately led by strategic management tools; projects are mostly executed through simple plans and schedules. The issues that this thesis addresses and solves involve the successful accompaniment of the construction project process through these strategic management tools. The second important aspect is an evaluation of project activity, which is mostly done through simple economic and technical valuation. However, during this research, effective strategic management tools are evaluated and suggested for the assessment of project activities. The research introduces a study of the current strategic management practices of construction companies and also presents the concept of strategic management and the areas that companies need to address to compete in the global market. A summary of an industry survey is documented along with the historical research that prompted the investigation of these topics with a focus on the implementation of tools. Strategic management is a concept that concerns making decisions and taking corrective actions to achieve the future goals and objectives of a company. The objective of this paper is to review the practice of strategic management in construction companies. Questionnaires were distributed to major construction companies listed under categories of each project capable of specifying the complete expression of strategic management tools. Findings of the research showed that the majority of development companies practice strategic management tools in the process and implementation of each tool.

Keywords: strategic management, management, analysis, project management

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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Authors: Rui Zhang

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Translation has been elevated to one of the key notions in contemporary cultural discourse for a wide range of fields. It focuses not only on communication or transmission of meaning between different languages, but also on ways in which the very act of translation can be understood as a metaphor for cultural process. In recent years, the notion of translation is employed by some contemporary Chinese artists in a conceptual way, whose works contribute to constructing/deconstructing global/local cultural discourse and their own cultural identities. This study examines two artworks by contemporary Chinese artist Gu Wenda from a translational perspective, namely Forest of Stone Steles - Retranslation & Rewriting of Tang Poetry and United Nations - China Monument: Temple of Heaven, aiming to broaden the scope of Translation Studies to investigate visual culture and enrich methodological approach to contemporary Chinese art. Focusing on the relationship between translation, visuality and materiality in these two works, this study explores the nature of translation as part of the production of cultural discourse in the age of globalization as well as a way of establishing cultural identity. Gu Wenda, one of the most prestigious artists in contemporary China, is considered a pioneer in ‘85 Art Movement of China, and thereafter he went abroad for his artistic pursuits. His transnational experience enriches his cultural identity and the underlying discourse constructed/deconstructed in many of his works. In the two works already mentioned, the concept of translation is deployed by Gu Wenda on both linguistic level and metaphorical level for artistic expression. These two works produce discourses in which the artist’s perception of cultural identity in a transnational context is articulated by the tension between source text and target text. Based on the conceptual framework of cultural identity proposed by Stuart Hall, analyses of Gu Wenda’s cultural identity revealed through translation in these two works are centred on two axes, i.e., the axis of similarity and continuity with Chinese intellectual culture and the axis of difference and rupture with it, and the dialogic relationship between these two vectors. It argues that besides serving as a means of constructing visuality in the two works, translation metaphorizes Gu Wenda’s journey from overcoming his cultural identity anxiety to re-establishing a transcultural identity embedded in the underlying discourse.

Keywords: contemporary Chinese art, cultural identity, transculturality, translation

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Authors: Mario J. Meco-Gutierrez, Francisco Perez-Hidalgo, Juan R. Heredia-Larrubia, Antonio Ruiz-Gonzalez, Francisco Vargas-Merino

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More and more applications power inverters connected to transformers, for example, the connection facilities to the power grid renewable generation. It is well known that the quality of signal power inverters it is not a pure sine. The harmonic content produced negative effects, one of which is the heating of electrical machines and therefore, affects the life of the machines. The decrease of life of transformers can be calculated by Arrhenius or Montsinger equation. Analyzing this expression any (long-term) decrease of a transformer temperature for 6º C - 7º C means doubles its life-expectancy. Methodologies: This work presents the technique of pulse width modulation (PWM) with an injection of harmonic and triangular frequency carrier modulated in frequency. This technique is used to improve the quality of the output voltage signal of the power inverters controlled PWM. The proposed technique increases in the fundamental term and a significant reduction in low order harmonics with the same commutations per time that control sine PWM. To achieve this, the modulating wave is compared to a triangular carrier with variable frequency over the period of the modulator. Therefore, it is, advantageous for the modulating signal to have a large amount of sinusoidal “information” in the areas of greater sampling. A triangular signal with a frequency that varies over the modulator’s period is used as a carrier, for obtaining more samples in the area with the greatest slope. A power inverter controlled by PWM proposed technique is connected to a transformer. Results: In order to verify the derived thermal parameters under different operation conditions, another ambient and loading scenario is involved for a further verification, which was sampled from the same power transformer. Temperatures of different parts of the transformer will be exposed for each PWM control technique analyzed. An assessment of the temperature be done with different techniques PWM control and hence the life of the transformer is calculated for each technique. Conclusion: This paper analyzes such as transformer heating produced by this technique and compared with other forms of PWM control. In it can be seen as a reduction the harmonic content produces less heat transformer and therefore, an increase in the life of the transformer.

Keywords: heating, power-inverter, PWM, transformer

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Authors: Sana Zia

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One of the most important questions for research on Muslim women's representation is the relationship between Islam and women’s situation in Islamic countries. In this context, certain questions can be raised like is it possible to analyze women’s situation in Islamic countries like Pakistan? Or what is the relationship between Islam and patriarchy? So this paper will examine all these questions by analysing Muslim women's representation in Pakistani Cinema. It is also significant to note that despite political and religious constraints in Muslim countries, in particular, Pakistan, women have not only been part of the film industry for long, but they also have chosen films as their feminist tool to question and expose the effects of patriarchy, religious fundamentalism, and gender-specific socio-cultural oppression. The religious-cultural ethos that could include gender-specific restrictions and limitations on their creative expression as Muslim women in an Islamic society. A new wave of Pakistani cinema is pivoting around strong Muslim female characters and opened up a new thought about Islamic women.Their contributions and success through this medium emphasized the need to investigate the significance and effectiveness of contemporary cinema as a tool of resistance and cross-cultural communication in a Muslim society. So this research can also provide a better understanding about Islam that needs to be modernized and reclaimed from the clutches of fundamentalism and extremism. This paper thus investigates the interrelation of women's representation and Pakistani cinema by analysing two films ‘Bol: To speak up’ and ‘Dukhter: Daughter’. The feminist analysis of these films not only helps to understand the new trends and dimensions in representation of Muslim women in Pakistani cinema, but this also helps to raise awareness globally regarding the depiction of Muslim women. So to foreground the above mentioned discussion, the films under study helps to evaluate their significance, the role they play towards activism, resistance, and global awareness in terms of what could be termed as a Muslim woman. The paper thus provides a valuable insight that how and why Islam is being used as a mechanism to merge social, political and economic factors to define the rights and conditions of Pakistani Muslim women and highlight the cinematic struggle of the film maker’s which by using films as an awareness tool are going to highlight the problems and issues of Muslim women in the global world.

Keywords: Muslim women, Pakistani cinema, patriarchy, religious fundamentalism

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Authors: Michael P. Mannino, Gerald W. Hart

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The majority of glucose metabolism proceeds through glycolytic pathways such as glycolysis or pentose phosphate pathway, however, about 5% is shunted through the hexosamine biosynthetic pathway, producing uridine diphosphate N-acetyl glucosamine (UDP-GlcNAc). This precursor can then be incorporated into complex oligosaccharides decorating the cell surface or remain as an intracellular post-translational-modification (PTM) of serine/threonine residues (O-GlcNAcylation, OGN), which has been identified on over 4,000 cytosolic or nuclear proteins. Intracellular OGN has major implications on cellularprocesses, typically by modulating protein localization, protein-protein interactions, protein degradation, and gene expression. Additionally, OGN is known to have an extensive cross-talk with phosphorylation, be in a competitive or cooperative manner. Unlike other PTMs there are only two cycling enzymes that are capable of adding or removing the GlcNAc moiety, O-linked N-aceytl glucosamine Transferase (OGT) and O-linked N-acetyl glucoamidase (OGA), respectively. The activity of OGT has been shown to be sensitive to cellular UDP-GlcNAc levels, even changing substrate affinity. Owing to this and that the concentration of UDP-GlcNAc is related to the metabolisms of glucose, amino acid, fatty acid, and nucleotides, O-GlcNAc is often referred to as a nutrient sensing rheostat. Indeed OGN is known to regulate several signaling pathways as a result of nutrient levels, such as insulin signaling. Dysregulation of OGN is associated with several disease states such as cancer, diabetes, and neurodegeneration. Improvements in glycomics over the past 10-15 years has significantly increased the OGT substrate pool, suggesting O-GlcNAc’s involvement in a wide variety of signaling pathways. However, O-GlcNAc’s role at the receptor level has only been identified in a case-by-case basis of known pathways. Examining the OGN of the plasma membrane (PM) may better focus our understanding of O-GlcNAc-effected signaling pathways. In this current study, PM fractions were isolated from several cell types via ultracentrifugation, followed by purification and MS/MS analysis in several cell lines. This process was repeated with or without OGT/OGA inhibitors or with increased/decreased glucose levels in media to ascertain the importance of OGN. Various pathways are followed up on in more detailed studies employing methods to localize OGN at the PM specifically.

Keywords: GlcNAc, nutrient sensitive, post-translational-modification, receptor

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