Search results for: gene relationships

Authors: Peter Fedichev

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We studied fundamental aspects of aging to develop a mathematical model of gene regulatory network. We show that aging manifests itself as an inherent instability of gene network leading to exponential accumulation of regulatory errors with age. To validate our approach we studied age-dependent omic data such as transcriptomes, metabolomes etc. of different model organisms and humans. We build a computational platform based on our model to identify the targets and biomarkers of aging to design new drugs against aging and age-related diseases. As biomarkers of aging, we choose the rate of aging and the biological age since they completely determine the state of the organism. Since rate of aging rapidly changes in response to an external stress, this kind of biomarker can be useful as a tool for quantitative efficacy assessment of drugs, their combinations, dose optimization, chronic toxicity estimate, personalized therapies selection, clinical endpoints achievement (within clinical research), and death risk assessments. According to our model, we propose a method for targets identification for further interventions against aging and age-related diseases. Being a biotech company, we offer a complete pipeline to develop an anti-aging drug-candidate.

Keywords: aging, longevity, biomarkers, senescence

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Authors: D. Leibman, D. Wolf, A. Gal-On

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Viral diseases of tomato crops result in heavy yield losses and may even jeopardize the production of these crops. Classical tomato breeding for disease resistance against Tomato yellow leaf curl virus (TYLCV), leads to partial resistance associated with a number of recessive genes. To author’s best knowledge Pepino mosaic virus (PepMV) genetic resistance is not yet available. The generation of viral resistance by means of genetic engineering was reported and implemented for many crops, including tomato. Transgenic resistance against viruses is based, in most cases, on Post Transcriptional Gene Silencing (PTGS), an endogenous mechanism which destroys the virus genome. In this work, we developed immunity against PepMV and TYLCV in a tomato based on a PTGS mechanism. Tomato plants were transformed with a hairpin-construct-expressed transgene-derived double-strand-RNA (tr-dsRNA). In the case of PepMV, the binary construct harbored three consecutive fragments of the replicase gene from three different PepMV strains (Italian, Spanish and American), to provide resistance against a range of virus strains. In the case of TYLCV, the binary vector included three consecutive fragments of the IR, V2 and C2 viral genes constructed in a hairpin configuration. Selected transgenic lines (T0) showed a high accumulation of transgene siRNA of 21-24 bases, and T1 transgenic lines showed complete immunity to PepMV and TYLCV. Graft inoculation displayed immunity of the transgenic scion against PepMV and TYLCV. The study presents the engineering of resistance in tomato against two serious diseases, which will help in the production of high-quality tomato. However, unfortunately, these resistant plants have not been implemented due to public ignorance and opposition against breeding by genetic engineering.

Keywords: PepMV, PTGS, TYLCV, tr-dsRNA

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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: Mohammad Alnabhan, Awni Hammouri, Mustafa Hammad, Anas Al-Badareen, Omamah Al-Thnebat

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Software visualization is one of the main techniques used to simplify the presentation of software systems and enhance their understandability. It is used to present the software system in a visual manner using simple, clear and meaningful symbols. This study proposes a new 2D software visualization approach. In this approach, each class is represented by rectangle, the name of the class placed above the rectangle, the size of class (Line of Code) represented by the height of the rectangle. The methods and the attributes are represented by circles and triangles respectively. The relationships among classes correspond to arrows. The proposed visualization approach was evaluated in terms of applicability and efficiency. Results have confirmed successful implementation of the proposed approach, and its ability to provide a simple and effective graphical presentation of extracted software components and properties.

Keywords: software visualization, software metrics, calling relationships, 2D graphs

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Authors: Abu Salim Mustafa

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Brucellosis is a zoonotic disease endemic in Kuwait. Human brucellosis can be caused by several Brucella species with Brucella melitensis causing the most severe and Brucella abortus the least severe disease. Furthermore, relapses are common after successful chemotherapy of patients. The classical biochemical methods of culture and serology for identification of Brucellae provide information about the species and serotypes only. However, to differentiate between relapse and reinfection/epidemiological investigations, the identification of genotypes using molecular methods is essential. In this study, four molecular methods [16S rRNA gene sequencing, real-time PCR, enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus variable-number tandem-repeat analysis (MLVA)-16] were evaluated for the identification and typing of 75 strains of Brucella isolated in Kuwait. The 16S rRNA gene sequencing suggested that all the strains were B. melitensis and real-time PCR confirmed their species identity as B. melitensis. The ERIC-PCR band profiles produced a dendrogram of 75 branches suggesting each strain to be of a unique type. The cluster classification, based on ~ 80% similarity, divided all the ERIC genotypes into two clusters, A and B. Cluster A consisted of 9 ERIC genotypes (A1-A9) corresponding to 9 individual strains. Cluster B comprised of 13 ERIC genotypes (B1-B13) with B5 forming the largest cluster of 51 strains. MLVA-16 identified all isolates as B. melitensis and divided them into 71 MLVA-types. The cluster analysis of MLVA-16-types suggested that most of the strains in Kuwait originated from the East Mediterranean Region, a few from the African group and one new genotype closely matched with the West Mediterranean region. In conclusion, this work demonstrates that B. melitensis, the most pathogenic species of Brucella, is prevalent in Kuwait. Furthermore, MLVA-16 is the best molecular method, which can identify the Brucella species and genotypes as well as determine their origin in the global context. Supported by Kuwait University Research Sector grants MI04/15 and SRUL02/13.

Keywords: Brucella, ERIC-PCR, MLVA-16, RT-PCR, 16S rRNA gene sequencing

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Authors: Zintle Kolo, Ndiko Ludidi

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The enzymatic activity of p-coumarate 3-hydroxylase (C3H) synthesize caffeic acid from p-coumaric acid. We recently showed that exogenously applied caffeic acid confers salinity tolerance in soybean (Glycine max) by inducing antioxidant enzymatic activity to promote enhanced scavenging or reactive oxygen species, thus limiting salinity-induced oxidative stress. Recent evidence also establishes that pre-treatment of plants with exogenously supplied caffeic acid improves plant tolerance to osmotic stress by improving plant antioxidant capacity and enhancing biosynthesis of compatible solutes. We aimed to identify a C3H in maize (Zea mays) and evaluate the effect of drought on the spatial and temporal expression of the gene encoding the candidate maize C3H (ZmC3H). Primary sequence analysis shows that ZmC3H shares 71% identity with an Arabidopsis thaliana C3H that is implicated in the control of Arabidopsis cell expansion, growth, and responses to stress. In silico ZmC3H promoter analysis reveals the presence of cis-acting elements that interact with transcription factors implicated in plant responses to drought. Spatial expression analysis by semi-quantitative RT-PCR shows that ZmC3H is expressed in both leaves and roots under normal conditions. However, drought represses the expression of ZmC3H in leaves whereas it up-regulates its expression in roots. These changes in ZmC3H expression correlate with the changes in the content of caffeic acid in maize in response to drought. We illustrate the implications of these changes in the expression of the gene in relation to maize responses to drought and discuss the potential of regulating caffeic acid biosynthesis towards genetic improvement of maize tolerance to drought stress. These findings have implications for food security because of the potential of the implications of the study for drought tolerance in maize.

Keywords: caffeic acid, drought-responsive expression, maize drought tolerance, p-coumarate 3-hydroxylase

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Authors: Rim Sghiri, Samia Al Shouli, Hana Benhassine, Nejla Elamri, Zahid Shakoor, Foued Slama, Adel Almogren, Hala Zeglaoui, Elyes Bouajina, Ramzi Zemni

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Objectives: Little is known about genes predisposing to systemic bone loss (SBL) in rheumatoid arthritis (RA). Therefore, we examined the association between SBL and a variant of CD40 gene, which is known to play a critical role in both immune response and bone homeostasis among patients with RA. Methods: CD40 rs48104850 was genotyped in 176 adult RA patients. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DXA). Results: Low BMD was observed in 116 (65.9%) patients. Among them, 60 (34.1%) had low femoral neck (FN) Z score, 72 (40.9%) had low total femur (TF) Z score, and 105 (59.6%) had low lumbar spine (LS) Z score. CD40 rs4810485 was found to be associated with reduced TF Z score with the CD40 rs4810485 T allele protecting against reduced TF Z score (OR = 0.40, 95% CI = 0.23-0.68, p = 0.0005). This association was confirmed in the multivariate logistic regression analysis (OR=0.31, 95% CI= 0.16-0.59, p=3.84 x 10₋₄). Moreover, median FN BMD was reduced among RA patients with CD40 rs4810485 GG genotype compared to RA patients harbouring CD40 rs4810485 TT and GT genotypes (0.788± 0.136 versus 0.826± 0.146g/cm², p=0.001). Conclusion: This study, for the first time ever, demonstrated an association between a CD40 genetic variant and SBL among patients with RA.

Keywords: rheumatoid arthritis, CD40 gene, bone mineral density, systemic bone loss, rs48104850

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Authors: A. M. Andriano, M. Lombardi, A. Lopolito, M. Prosperi, A. Stasi, E. Iannuzzi

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In according to the scientific debate on the definition of Social Innovation (SI), the present paper identifies SI as new ideas (products, services, and models) that simultaneously meet social needs and create new social relationships or collaborations. This concept offers important tools to unravel the difficult condition for the agricultural sector in marginalized areas, characterized by the abandonment of activities, low level of farmer education, and low generational renewal, hampering new territorial strategies addressed at and integrated and sustainable development. Models of SI in agriculture, starting from bottom up approach or from the community, are considered to represent the driving force of an ecological and digital revolution. A system based on SI may be able to grasp and satisfy individual and social needs and to promote new forms of entrepreneurship. In this context, Vazapp ('Go Hoeing') is an emerging SI model in southern Italy that promotes solutions for satisfying needs of farmers and facilitates their relationships (creation of network). The Vazapp’s initiative, considered in this study, is the Contadinners ('Farmer’s dinners'), a dinner held at farmer’s house where stakeholders living in the surrounding area know each other and are able to build a network for possible future professional collaborations. The aim of the paper is to identify the evolution of farmers’ relationships, both quantitatively and qualitatively, because of the Contadinner’s initiative organized by Vazapp. To this end, the study adopts the Social Network Analysis (SNA) methodology by using UCINET (Version 6.667) software to analyze the relational structure. Data collection was realized through a questionnaire distributed to 387 participants in the twenty 'Contadinners', held from February 2016 to June 2018. The response rate to the survey was about 50% of farmers. The elaboration data was focused on different aspects, such as: a) the measurement of relational reciprocity among the farmers using the symmetrize method of answers; b) the measurement of the answer reliability using the dichotomize method; c) the description of evolution of social capital using the cohesion method; d) the clustering of the Contadinners' participants in followers and not-followers of Vazapp to evaluate its impact on the local social capital. The results concern the effectiveness of this initiative in generating trustworthy relationships within the rural area of southern Italy, typically affected by individualism and mistrust. The number of relationships represents the quantitative indicator to define the dimension of the network development; while the typologies of relationships (from simple friendship to formal collaborations, for branding new cooperation initiatives) represents the qualitative indicator that offers a diversified perspective of the network impact. From the analysis carried out, Vazapp’s initiative represents surely a virtuous SI model to catalyze the relationships within the rural areas and to develop entrepreneurship based on the real needs of the community.

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Authors: Tamriko Pavliashvili

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Marriage is such an important institution of family law, which is an indicator of the development of society. Although a family can be created by the birth of a child between an unmarried couple, marriage is still the main basis for the creation of a family, during which the rights and duties imposed require legal regulation. At present, in the conditions of globalization, there are different types of marriage, although in the main countries, it is still a union of a woman and a man, which involves voluntary cohabitation and assuming and fulfilling the norms and responsibilities established on the basis of the law. Modern society is at the stage where there is a need to create a family, and therefore marriage provides the best opportunity for relationships and existence between people. The mentioned paper about the state institution - marriage gives us the opportunity to get more information about the existing habits, legal norms from the ancient times to the modern period in Georgia, and also through comparison we will see what the differences and commonalities were and are in the marriage law of the countries of the world and Georgia.

Keywords: marriage, family law, the union of man and woman, church law

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Authors: Vincent Murray

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The chromatin structure at the transcription start sites (TSSs) of genes is very important in the control of gene expression. In order for gene expression to occur, the chromatin structure at the TSS has to be altered so that the transcriptional machinery can be assembled and RNA transcripts can be produced. In particular, the nucleosome structure and positioning around the TSS has to be changed. Bleomycin is utilized as an anti-tumor agent to treat Hodgkin's lymphoma, squamous cell carcinoma, and testicular cancer. Bleomycin produces DNA damage in human cells and DNA strand breaks, especially double-strand breaks, are thought to be responsible for the cancer chemotherapeutic activity of bleomycin. Bleomycin is a large glycopeptide with molecular weight of approximately 1500 Daltons and hence its DNA strand cleavage activity can be utilized as a probe of chromatin structure. In this project, Illumina next-generation DNA sequencing technology was used to determine the position of DNA double-strand breaks at the TSSs of genes in intact cells. In this genome-wide study, it was found that bleomycin cleavage preferentially occurred at the TSSs of actively transcribed human genes in comparison with non-transcribed genes. There was a correlation between the level of enhanced bleomycin cleavage at TSSs and the degree of transcriptional activity. In addition, bleomycin was able to determine the position of nucleosomes at the TSSs of human genes. Bleomycin analogues were also utilized as probes of chromatin structure at the TSSs of human genes. In a similar manner to bleomycin, the bleomycin analogues 6′-deoxy-BLM Z and zorbamycin preferentially cleaved at the TSSs of human genes. Interestingly this degree of enhanced TSS cleavage inversely correlated with the cytotoxicity (IC50 values) of BLM analogues. This indicated that the degree of cleavage by bleomycin analogues at the TSSs of human genes was very important in the cytotoxicity of bleomycin and analogues. It also provided a deeper insight into the mechanism of action of this cancer chemotherapeutic agent since actively transcribed genes were preferentially targeted.

Keywords: anti-cancer activity, chromatin structure, cytotoxicity, gene expression, next-generation DNA sequencing

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Authors: Nada Souissi, Mourad Mroua

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The main purpose of this study is to examine the interaction between financial asset volatility, economic factors and investor's behavioral indicators related to both the company's and the markets stocks for the period from January 2000 to January2020. Using multiple linear regression and Bayesian Networks modeling, results show a positive and negative relationship between investor's psychology index, economic factors and predicted stock market return. We reveal that the application of the Bayesian Discrete Network contributes to identify the different cause and effect relationships between all economic, financial variables and psychology index.

Keywords: Financial asset return predictability, Economic factors, Investor's psychology index, Bayesian approach, Probabilistic networks, Parametric learning

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Authors: Deepak Kumar, Ravi Rajwanshi, Mohd. Aslam Yusuf, Nisha Kant Pandey, Preeti Singh, Mukesh Saxena, Neera Bhalla Sarin

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Global issues are leading to concerns over food security. These include climate change, urbanization, increase in population subsequently leading to greater energy and water demand. Futuristic approach for crop improvement involves gene pyramiding for agronomic traits that empower the plants to withstand multiple stresses. In an earlier study from the laboratory, the efficacy of overexpressing γ-tocopherol methyl transferase (γ-TMT) gene from the vitamin E biosynthetic pathway has been shown to result in six-fold increase of the most biologically active form, the α-tocopherol in Brassica juncea which resulted in alleviation of salt, heavy metal and osmoticum induced stress by the transgenic plants. The glyoxalase I (gly I) gene from the glyoxalase pathway has also been earlier shown by us to impart tolerance against multiple abioitc stresses by detoxification of the cytotoxic compound methylglyoxal in Brassica juncea. Recently, both the transgenes were pyramided in Brassica juncea lines through sexual crosses involving two stable Brassica juncea lines overexpressing γ-TMT and gly I genes respectively. The transgene integration was confirmed by PCR analysis and their mRNA expression was evident by RT-PCR analysis. Preliminary physiological investigations showed ~55% increased seed germination under 200 mM NaCl stress in the pyramided line and 81% higher seed germination under 200 mM mannitol stress as compared to the WT control plants. The pyramided lines also retained more chlorophyll content when the leaf discs were floated on NaCl (200, 400 and 600 mM) or mannitol (200, 400 and 600 mM) compared to the WT control plants. These plants had higher Relative Water Content and greater solute accumulation under stress compared to the parental plants having γ-TMT or the glyI gene respectively. The studies revealed the synergy of two components from different metabolic pathways in enhancing stress hardiness of the transgenic B. juncea plants. It was concluded that pyramiding of genes (γ-TMT and glyI) from diverse pathways can lead to enhanced tolerance to salt and mannitol stress (simulating drought conditions). This strategy can prove useful in enhancing the crop yields under various abiotic stresses.

Keywords: abiotic stress, brassica juncea, glyoxalase I, α-tocopherol

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Authors: Muhammad Farooq Baig, Saleem Qadeer

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Background: The frequency of hepatitis C virus infection along with tuberculosis has not been widely investigated and very low statistics on rates of hepatitis C virus co-infection in tuberculosis patients. Hepatotoxicity is the major side effect of anti-tuberculosis therapy hepatitis HCVliver disease elevates the chances of hepatotoxicity up-to five folds. Objectives & Aim: To see the frequency of Hepatitis Cvirus infection amongst people with diagnosed Tuberculosis using gene X-pert technique. To evaluate the factors associated with HCVinfection in patients with MTBtuberculosis and to determine sensitivity and specificity of the tests. Study design: Comparative analytical study. Methodology: Three hundred and thirteen patients of tuberculosis diagnosed by Genexpert included while testing hepatitis C virus using immunochromotography rapid test technique, enzyme linked immunosorbent assay method and polymerase chain reaction test for confirmation. Results:Higher frequency of tuberculosis infection in males 57.8%, 42.5% between 20-39 years and 22% of hepatitis C virus infection in tuberculosis patients.The sensitivity of rapid test and enzyme-linked immunosorbent assay was 79% and 96% respectively while the specificity of rapid test and enzyme-linked immunosorbent assay was 91% and 99% respectively.

Keywords: Mycobactrium Tuberculosis, PC'R, Gene x pert, Hepatitis C virus

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Authors: Seraj Makkawi, Abdulaziz A. Alqarni, Himyan Alghaythee, Suzan Y. Alharbi, Anmar Fatani, Reem Adas, Ahmad R. Abuzinadah

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Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disease that involves both the upper and lower motor neurons. Familial ALS, including superoxide dismutase 1 (SOD1) mutation, accounts for 5-10% of all cases of ALS. Typically, the symptoms of ALS are purely motor, though coexistent sensory symptoms have been reported in rare cases. In this report, we describe the case of a 47- year-old man who presented with progressive bilateral lower limb weakness and numbness for the last four years. A nerve conduction study (NCS) showed evidence of coexistent axonal sensorimotor polyneuropathy in addition to the typical findings of ALS in needle electromyography. Genetic testing confirmed the diagnosis of familial ALS secondary to the SOD1 genetic mutation. This report highlights that the presence of sensory symptoms should not exclude the possibility of ALS in an appropriate clinical setting.

Keywords: Saudi Arabia, polyneuropathy, SOD1 gene mutation, familial amyotrophic lateral sclerosis, amyotrophic lateral sclerosis

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Authors: Titus A. Beu

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Many modern gene-delivery protocols rely on condensed complexes of DNA with polycations to introduce the genetic payload into cells by endocytosis. In particular, polyethyleneimine (PEI) stands out by a high buffering capacity (enabling the efficient condensation of DNA) and relatively simple fabrication. Realistic computational studies can offer essential insights into the formation process of DNA-PEI polyplexes, providing hints on efficient designs and engineering routes. We present comprehensive computational investigations of solvated PEI and DNA-PEI polyplexes involving calculations at three levels: ab initio, all-atom (AA), and coarse-grained (CG) molecular mechanics. In the first stage, we developed a rigorous AA CHARMM (Chemistry at Harvard Macromolecular Mechanics) force field (FF) for PEI on the basis of accurate ab initio calculations on protonated model pentamers. We validated this atomistic FF by matching the results of extensive molecular dynamics (MD) simulations of structural and dynamical properties of PEI with experimental data. In a second stage, we developed a CG MARTINI FF for PEI by Boltzmann inversion techniques from bead-based probability distributions obtained from AA simulations and ensuring an optimal match between the AA and CG structural and dynamical properties. In a third stage, we combined the developed CG FF for PEI with the standard MARTINI FF for DNA and performed comprehensive CG simulations of DNA-PEI complex formation and condensation. Various technical aspects which are crucial for the realistic modeling of DNA-PEI polyplexes, such as options of treating electrostatics and the relevance of polarizable water models, are discussed in detail. Massive CG simulations (with up to 500 000 beads) shed light on the mechanism and provide time scales for DNA polyplex formation independence of PEI chain size and protonation pattern. The DNA-PEI condensation mechanism is shown to primarily rely on the formation of DNA bundles, rather than by changes of the DNA-strand curvature. The gained insights are expected to be of significant help for designing effective gene-delivery applications.

Keywords: DNA condensation, gene-delivery, polyethylene-imine, molecular dynamics.

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Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa

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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.

Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology

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Authors: Anum Rafiq

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Adolescence is a vulnerable period for youth across the world. It is a period of new learning with opportunities to understand and develop perspectives on health and well-being. With youth beginning to engage in intimate relationships at an earlier age in the 21st century, concentrating on the learning opportunity they have in school is paramount. The nature of what has been deemed important to teach in schools has changed throughout history, and the focus has shifted from home/family skills to teaching youth how to be competitive in the job market. Amidst this emphasis, opportunities for them exist to learn about building healthy intimate relationships, one of the foundational elements of most people’s lives. Using an Institutional Ethnography (IE), the lived experiences of youth in how they understand intimate relationships and how their learning experience is organized through the high school Health and Physical Education (H&PE) course is explored. An empirical inquiry into how the actual work of teachers and youth are socially organized by a biomedical, employment-related, and efficiency-based discourse is provided. Through thirty-two qualitative interviews with teachers and youth, a control of ruling relations such as institutional accountability circuits, performance reports, and timetabling over the experience of teachers and youth is found. One of the facets of the institutional accountability circuit is through the social organization of teaching and learning about healthy intimate relationships being framed through a biomedical discourse. In addition, the role of a hyper-focus on performance and evaluation is found as paramount in situating healthy intimacy discussions as inferior to neoliberally charged productivity measures such as employment skills. Lastly, due to the nature of institutional policies such as regulatory guidelines, teachers are largely influenced to avoid diving into discussions deemed risky or taboo by society, such as healthy intimacy in adolescence. The findings show how texts such as the H&PE curriculum, the Ontario College of Teachers (OCT) guidelines, Ministry of Education Performance Reports, and the timetable organize the day-to-day activities of teachers and students and reproduce different disjunctures for youth. This disjuncture includes some of their experiences being subordinated, difficulty relating to curriculum, and an experience of healthy living discussions being skimmed over across sites. The findings detail that the experience of youth in learning about healthy intimate relationships is not akin to the espoused vision outlined in policy documents such as the H&PE (2015) curriculum policy. These findings have implications for policymakers, activists, and school administration alike, which call for an investigation into who is in power when it comes to youth’s learning needs, as a pivotal period where youth can be equipped with life-changing knowledge is largely underutilized. A restructuring of existing institutional practices that allow for the social and institutional flexibility required to broach the topic of healthy intimacy in a comprehensive manner is required.

Keywords: health policy, intimate relationships, youth, education, ruling relations, sexual education, violence prevention

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Authors: Murat Erdoğdu, Murat Koçyiğit

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Brand image and brand loyalty are among the most important relational marketing elements for brand owners to be able to set up long – term relationships with their customers and to maintain these relationships. Brand owners improve their brand images with the positive perceptions remaining in the consumers’ minds. In addition, they try to find the customers that are both emotionally and behaviourally faithful to themselves in order to set up long – term relationships. Therefore, the aim of this study is to analyse the effects of the brand image that has a very important role among relational marketing elements on the brand loyalty in terms of the variables such as the perceived value, the trust in brand and the brand satisfaction. In this context, a conceptual model was created to determine the effect of the brand image on the brand loyalty thanks to the Structural Equation Model (SEM). According to this aim and this model, the study was carried out in the scope of the data collected through the questionnaires in Konya with the method of convenience sampling. The results of the research showed that the brand image has positive significant effects on the perceived value and the trust in brand and that the trust in brand has positive significant effects on the brand satisfaction, and that the brand satisfaction has positive significant effects on the brand loyalty. Thus, the hypotheses that the brand image has direct effects on the perceived value and the trust in brand and that the trust in brand has direct effects on the brand satisfaction and that the brand satisfaction has direct effects on the brand loyalty were supported. In addition, the findings about whether the perceived value has a significant effect on the brand satisfaction were also acquired.

Keywords: brand image, brand loyalty, perceived value, satisfaction, trust

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Authors: Kamila Weissova, Jitka Skrabalova, Katerina Skalova, Jana Koprivova, Zdenka Bendova

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Any Arctic visitor has to deal with extreme conditions, including constant light during the summer season or constant darkness during winter time. Light/dark cycle is the most powerful synchronizing signal for biological clock and the absence of daily dark period during the polar day can significantly alter the functional state of the internal clock. However, the inner clock can be synchronized by other zeitgebers such as physical activity, food intake or social interactions. Here, we investigated the effect of polar day on circadian clock of 10 researchers attending the polar base station in the Svalbard region during July. The data obtained on Svalbard were compared with the data obtained before the researchers left for the expedition (in the Czech Republic). To determine the state of circadian clock we used wrist actigraphy followed by sleep diaries, saliva, and buccal mucosa samples, both collected every 4 hours during 24h-interval to detect melatonin by radioimmunoassay and clock gene (PER1, BMAL1, NR1D1, DBP) mRNA levels by RT-qPCR. The clock gene expression was analyzed using cosinor analysis. From our results, it is apparent that the constant sunlight delayed melatonin onset and postponed the physical activity in the same order. Nevertheless, the clock gene expression displayed higher amplitude on Svalbard compared to the amplitude detected in the Czech Republic. These results have suggested that the common daily schedule at the Svalbard expedition can strengthen circadian rhythm in the environment that is lacking light/dark cycle. In conclusion, the constant sunlight delays melatonin onset, but it still maintains its rhythmic secretion. The effect of constant sunlight on circadian clock can be minimalized by common daily scheduled activity.

Keywords: actighraph, clock genes, human, melatonin, polar day

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Authors: Lutfurrahman Aftab

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The Taliban’s relationships with the neighboring countries are a complex political issue that local people interpret one way, and politicians have different perceptions; therefore, it is a current issue that needs to be analyzed broadly and impartially. In this article, the writer investigates the Taliban’s current relationships with the neighboring countries, as well as looking at the effects these relationships have on the current peace negotiations in Doha, which began on September 12, 2020. The issue of Taliban and the current peace process has turned to be the center-of-attention for most of the neighboring countries, and every country has opened new pages in their foreign policies because after the Taliban-US peace agreement, the neighboring countries are meticulously and closely observing the situation and they believe that the Taliban are on the verge to tighten their grips on the future political power of Afghanistan. Every neighboring country of Afghanistan has political, economic, and social interests in this land-locked country. The Taliban’s current role within the peace talks and anticipated future position within the Afghan government will have great political, economic, and social implications on countries in the region as they assess their foreign policies. As these countries move to form closer ties with the Taliban, the government of Afghanistan is worried that this may hinder the peace process. Afghanistan has long blamed Pakistan for sheltering the Taliban and providing safe havens for the terrorist groups, including Al Qaeda, and the recent visits of Taliban’s delegations to Islamabad, Pakistan, have raised concern among government officials in Afghanistan who believe that the Taliban are not independent in their decisions, and for every step they take, are consulting with Pakistan’s political leadership.

Keywords: peace process, USA, Afghanistan, Taliban

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Authors: Khandaker Fariha Ahmed, Md. Noman Munshi, Tarin Sultana, Md. Zoynul Abedin

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Suitability number (SN) is perhaps one of the most important parameters of coarse-grained soil in assessing its appropriateness to use as a backfill in retaining structures, sand compaction pile, Vibro compaction, and other similar foundation and ground improvement works. Though determined in an empirical manner, it is imperative to study SN to understand its relation with other aggregate properties like fineness modulus (FM), and strength and density properties of sandy soil. The present paper reports the findings of the study on the examination of the properties of sandy soil, as mentioned. Random numbers were generated to obtain the percent fineness on various sieve sizes, and fineness modulus and suitability numbers were predicted. Sand samples were collected from the field, and test samples were prepared to determine maximum density, minimum density and shear strength parameter φ against particular fineness modulus and corresponding suitability number Five samples of SN value of excellent (0-10) and three samples of SN value fair (20-30) were taken and relevant tests were done. The data obtained from the laboratory tests were statistically analyzed. Results show that with the increase of SN, the value of FM decreases. Within the SN value rated as excellent (0-10), there is a decreasing trend of φ for a higher value of SN. It is found that SN is dependent on various combinations of grain size properties like D10, D30, and D20, D50. Strong linear relationships were obtained between SN and FM (R²=.0.93) and between SN value and φ (R²=.94). Correlation equations are proposed to define relationships among SN, φ, and FM.

Keywords: density, fineness modulus, shear strength parameter, suitability number

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Authors: Nivedita Ghosh

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This paper undertakes an analysis of permissions that are required by documentary filmmakers in order to access the locations and respondents that they desire to film. The attempt is to bring out the manner in which the practice of documentary filmmaking becomes embedded within complex social structures and relationships within/around which the film is being made. These social relationships may not only influence the direction that the film takes with respect to its final story, but may also impact the very method of filmmaking undertaken by the filmmaker. The following essay presents four types of filmmaking permissions, each revealing the specific social dynamics between the filmmaker and the filmed, and intra social dynamics between those who are intended to be filmed. The analysis shows how documentary filmmaking permissions derive from the community norms and values of the respondents. The paper is based on fieldwork carried out amongst documentary filmmakers filming in Delhi and Gujarat in India and Sardinia, Italy.

Keywords: documentary film, documentary film shooting, India, permissions

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Authors: Anna D. Kotrova, Alexandr N. Shishkin, Elena I. Ermolenko

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The aim. To study the quantitative and qualitative colon bacteria ratio from patients with metabolic syndrome. Materials and methods. Fecal samples from patients of 2 groups were identified and analyzed: the first group was formed by patients with metabolic syndrome, the second one - by healthy individuals. The metagenomics method was used with the analysis of 16S rRNA gene sequences. The libraries of the variable sites (V3 and V4) gene 16S RNA were analyzed using the MiSeq device (Illumina). To prepare the libraries was used the standard recommended by Illumina, a method based on two rounds of PCR. Results. At the phylum level in the microbiota of patients with metabolic syndrome compared to healthy individuals, the proportion of Tenericutes was reduced, the proportion of Actinobacteria was increased. At the genus level, in the group with metabolic syndrome, relative to the second group was increased the proportion of Lachnospira. Conclusion. Changes in the colon bacteria ratio in the gut microbiota of patients with metabolic syndrome were found both at the type and the genus level. In the metabolic syndrome group, there is a decrease in the proportion of bacteria that do not have a cell wall. To confirm the revealed microbiota features in patients with metabolic syndrome, further study with a larger number of samples is required.

Keywords: gut microbiota, metabolic syndrome, metagenomics, tenericutes

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Authors: Thanawit Buafai, Siyathorn Khunon

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This paper aims to explore the satisfaction levels of tourism product components on the island of Samui by studying the cultural dimension relationships of Hofsted’s classic theory. Both the six Hofsted cultural dimensions and tourism production satisfaction measures have been of interest worldwide. Therefore, the challenge of this study is to re-confirm previous research results in the ever-changing current contexts of the modern globalized business era. Self-rated questionnaires were employed to collect data from six nationalities of tourists in Samui, totaling 386 samples. The reliability of this research methodology was 0.967. Correlation was applied to analyze the relationships. The results indicate that Masculinity is significantly related to tourism destination satisfaction for every factor, while the other five cultural dimensions are related to some factors of tourism satisfaction. Surprisingly, tourist satisfaction toward the bar/restaurant factor is significantly correlated with all six cultural dimensions.

Keywords: cultural dimensions, tourism products, Samui, Thailand

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Authors: Theresia El Khoury, Georges Badr, Amir Hajjam El Hassani, Stéphane N’Guyen Van Ky

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The widespread adoption of machine learning and artificial intelligence across different domains can be attributed to the digitization of data over several decades, resulting in vast amounts of data, types, and structures. Thus, data processing and preparation turn out to be a crucial stage. However, applying these techniques to S1000D standard-based data poses a challenge due to its complexity and the need to preserve logical information. This paper describes SALERNO, an S1000d AppLicability dEpended pRocessiNg mOdel. This python-based model analyzes and converts the XML S1000D-based files into an easier data format that can be used in machine learning techniques while preserving the different logic and relationships in files. The model parses the files in the given folder, filters them, and extracts the required information to be saved in appropriate data frames and Excel sheets. Its main idea is to group the extracted information by applicability. In addition, it extracts the full text by replacing internal and external references while maintaining the relationships between files, as well as the necessary requirements. The resulting files can then be saved in databases and used in different models. Documents in both English and French languages were tested, and special characters were decoded. Updates on the technical manuals were taken into consideration as well. The model was tested on different versions of the S1000D, and the results demonstrated its ability to effectively handle the applicability, requirements, references, and relationships across all files and on different levels.

Keywords: aeronautics, big data, data processing, machine learning, S1000D

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Yuan-Yu Chiang, Yu-Han Tseng, Chin-Chen Wen

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Many southeast-Asia women migrate to Taiwan by marriage, and it usually takes 4 to 8 years for them to acquire Taiwanese citizenship. This study investigates the relationships between their citizenship acquisition and whether they develop Taiwanese identities. One hundred and ninety-two immigrant women were measured using Multigroup Ethnic Identity Measure-Revised and a global 10-point ethnic identity question. Correlation tests and hierarchical regression were performed to explore whether acquiring citizenship would help immigrant women to develop Taiwanese identities. The results revealed that citizenship acquisition does help immigrant women to identify with Taiwanese society symbolically. However, the results also indicated that acquiring citizenship would not help these immigrant women become involved in deeper cultural exploration of Taiwan nor would it encourage them to make commitments to the host society.

Keywords: immigrants, international marriage, ethnic identity, Taiwan

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Authors: Shri Krishna Mishra

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In an educational context, technology can prompt interactive plight only when it is used in conjunction with interactive plight methods. This study, therefore, examines the relationships among components that contribute to higher levels of interactive plight and execution, such as interactive Plight methods, technology, intrinsic motivation and deep learning. 526 students participated in this study. With structural equation modelling, the authors test the conceptual model and identify satisfactory model fit. The results indicate that interactive Plight methods, technology and intrinsic motivation have significant relationship with interactive Plight; deep learning mediates the relationships of the other variables with Execution.

Keywords: searching the relationship among components, contribute to interactive plight, educational execution, intrinsic motivation

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Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie Teklu

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Recent developments in targeted genome editing accelerated genetic research and opened new potentials to improve crops for better yields and quality. Given the significance of cereal crops as a primary source of food for the global population, the utilization of contemporary genome editing techniques like CRISPR/Cas9 is timely and crucial. CRISPR/Cas technology has enabled targeted genomic modifications, revolutionizing genetic research and exploration. Application of gene editing through CRISPR/Cas9 in enhancing sorghum is particularly vital given the current ecological, environmental, and agricultural challenges exacerbated by climate change. As sorghum is one of the main staple foods of our region and is known to be a resilient crop with a high potential to overcome the above challenges, the application of genome editing technology will enhance the investigation of gene functionality. CRISPR/Cas9 enables the improvement of desirable sorghum traits, including nutritional value, yield, resistance to pests and diseases, and tolerance to various abiotic stresses. Furthermore, CRISPR/Cas9 has the potential to perform intricate editing and reshape the existing elite sorghum varieties, and introduce new genetic variations. However, current research primarily focuses on improving the efficacy of the CRISPR/Cas9 system in successfully editing endogenous sorghum genes, making it a feasible and successful undertaking in sorghum improvement. Recent advancements and developments in CRISPR/Cas9 techniques have further empowered researchers to modify additional genes in sorghum with greater efficiency. Successful application and advancement of CRISPR techniques in sorghum will aid not only in gene discovery and the creation of novel traits that regulate gene expression and functional genomics but also in facilitating site-specific integration events. The purpose of this review is, therefore, to elucidate the current advances in sorghum genome editing and highlight its potential in addressing food security issues. It also assesses the efficiency of CRISPR-mediated improvement and its long-term effects on crop improvement and host resistance against parasites, including tissue-specific activity and the ability to induce resistance. This review ends by emphasizing the challenges and opportunities of CRISPR technology in combating parasitic plants and proposing directions for future research to safeguard global agricultural productivity.

Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield

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Authors: Shagufta Jabeen, Faez Jesse Firdaus Abdullah, Zunita Zakaria, Nurulfiza Mat Isa, Yung Chie Tan, Wai Yan Yee, Abdul Rahman Omar

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Pasteurella multocida is associated with acute, as well as, chronic infections in avian and bovine such as pasteurellosis and hemorrhagic septicemia (HS) in cattle and buffaloes. Iron is one of the most important nutrients for pathogenic bacteria including Pasteurella and acts as a cofactor or prosthetic group in several essential enzymes and is needed for amino acid, pyrimidine, and DNA biosynthesis. In our recent study, we showed that 2% of Pasteurella multocida serotype A strain PMTB2.1 encode for iron regulating genes (Accession number CP007205.1). Genome sequencing of other Pasteurella multocida serotypes namely PM70 and HB01 also indicated up to 2.5% of the respective genome encode for iron regulating genes, suggesting that Pasteurella multocida genome comprises of multiple systems for iron uptake. Since P. multocida PMTB2.1 has more than 40 CDs out of 2097 CDs (approximately 2%), encode for iron-regulated. The gene expression profiling of four iron-regulating genes namely fbpb, yfea, fece and fur were characterized under iron-restricted environment. The P. multocida strain PMTB2.1 was grown in broth with and without iron chelating agent and samples were collected at different time points. Relative mRNA expression profile of these genes was determined using Taqman probe based real-time PCR assay. The data analysis, normalization with two house-keeping genes and the quantification of fold changes were carried out using Bio-Rad CFX manager software version 3.1. Results of this study reflect that iron reduced environment has significant effect on expression profile of iron regulating genes (p < 0.05) when compared to control (normal broth) and all evaluated genes act differently with response to iron reduction in media. The highest relative fold change of fece gene was observed at early stage of treatment indicating that PMTB2.1 may utilize its periplasmic protein at early stage to acquire iron. Furthermore, down-regulation expression of fece with the elevated expression of other genes at later time points suggests that PMTB2.1 control their iron requirements in response to iron availability by down-regulating the expression of iron proteins. Moreover, significantly high relative fold change (p ≤ 0.05) of fbpb gene is probably associated with the ability of P. multocida to directly use host iron complex such as hem, hemoglobin. In addition, the significant increase (p ≤ 0.05) in fbpb and yfea expressions also reflects the utilization of multiple iron systems in P. multocida strain PMTB2.1. The findings of this study are very much important as relative scarcity of free iron within hosts creates a major barrier to microbial growth inside host and utilization of outer-membrane proteins system in iron acquisition probably occurred at early stage of infection with P. multocida. In conclusion, the presence and utilization of multiple iron system in P. multocida strain PMTB2.1 revealed the importance of iron in the survival of P. multocida.

Keywords: iron-related genes, real-time PCR, gene expression profiling, fold changes

Procedia PDF Downloads 458