Search results for: gene relationships

Authors: Ruwani N. Nugara, Masashi Inafuku, Kensaku Takara, Hironori Iwasaki, Hirosuke Oku

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Pteryxin from the partially purified hexane phase (HP) of Peucedanum japonicum Thunb (PJT) was identified as the active compound related to anti-obesity. Thus, in this study we investigated the mechanisms related to anti-obesity activity in-vitro. The HP was fractionated, and effect on the triglyceride (TG) content was evaluated in 3T3-L1 and HepG2 cells. Comprehensive spectroscopic analyses were used to identify the structure of the active compound. The dose dependent effect of active constituent on the TG content, and the gene expressions related to adipogenesis, fatty acid catabolism, energy expenditure, lipolysis and lipogenesis (20 μg/mL) were examined in-vitro. Furthermore, higher dosage of pteryxin (50μg/mL) was tested against 20μg/mL in 3T3-L1 adipocytes. The mRNA were subjected to SOLiD next generation sequencer and the obtained data were analyzed by Ingenuity Pathway Analysis (IPA). The active constituent was identified as pteryxin, a known compound in PJT. However, its biological activities against obesity have not been reported previously. Pteryxin dose dependently suppressed TG content in both 3T3-L1 adipocytes and HepG2 hepatocytes (P < 0.05). Sterol regulatory element-binding protein-1 (SREBP1 c), Fatty acid synthase (FASN), and acetyl-CoA carboxylase-1 (ACC1) were downregulated in pteryxin-treated adipocytes (by 18.0, 36.1 and 38.2%; P < 0.05, respectively) and hepatocytes (by 72.3, 62.9 and 38.8%, respectively; P < 0.05) indicating its suppressive effects on fatty acid synthesis. The hormone-sensitive lipase (HSL), a lipid catabolising gene was upregulated (by 15.1%; P < 0.05) in pteryxin-treated adipocytes suggesting improved lipolysis. Concordantly, the adipocyte size marker gene, paternally expressed gene1/mesoderm specific transcript (MEST) was downregulated (by 42.8%; P < 0.05), further accelerating the lipolytic activity. The upregulated trend of uncoupling protein 2 (UCP2; by 77.5%; P < 0.05) reflected the improved energy expenditure due to pteryxin. The 50μg/mL dosage of pteryxin completely suppressed PPARγ, MEST, SREBP 1C, HSL, Adiponectin, Fatty Acid Binding Protein (FABP) 4, and UCP’s in 3T3-L1 adipocytes. The IPA suggested that pteryxin at 20μg/mL and 50μg/mL suppress obesity in two different pathways, whereas the WNT signaling pathway play a key role in the higher dose of pteryxin in preadipocyte stage. Pteryxin in PJT play the key role in regulating lipid metabolism related gene network and improving energy production in vitro. Thus, the results suggests pteryxin as a new natural compound to be used as an anti-obesity drug in pharmaceutical industry.

Keywords: obesity, peucedanum japonicum thunb, pteryxin, food science

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Authors: Bella Llego

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This study aims to investigate the relationships between human resource management and entrepreneurship in the view of owner-managers and employees, and among employees with in the SME in Thailand. The research method used a qualitative method to confirm the phenomenology interest with top management position which women are regarding their career path by using purposive sampling method. The results showed that human resources management has positive relate with the corporate entrepreneurship are including the recruitment process, training worker, professional career development and reward system impact to entrepreneur’s knowledge and innovation of corporate entrepreneurship in respectively to bring a very reliable way. Then, the key informant suggested that women’s career experiences predisposed them to find an alternative route for entrepreneurship, despite having achieved top management. The understanding factors that successfully contribute to the development of women entrepreneurs from career development perspective are critical endeavours for any type of organization as well.

Keywords: entrepreneurship, firm performance, human resource management, work efficiency

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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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 - of marriage gives us the opportunity to get more information about the existing habits and legal norms from 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, concubinage, registered marriage, impeding circumstances, positive and negative conditions of marriage

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Authors: L. K. Davis

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The effects of the evolution force are observable in nature at all structural levels ranging from small molecular systems to conversely enormous biospheric systems. However, the evolution force and work associated with formation of biological structures has yet to be described mathematically or theoretically. In addressing the conundrum, we consider evolution from a unique perspective and in doing so we introduce the “Fundamental Theory of the Evolution Force: FTEF”. We utilized synthetic evolution artificial intelligence (SYN-AI) to identify genomic building blocks and to engineer 14-3-3 ζ docking proteins by transforming gene sequences into time-based DNA codes derived from protein hierarchical structural levels. The aforementioned served as templates for random DNA hybridizations and genetic assembly. The application of hierarchical DNA codes allowed us to fast forward evolution, while dampening the effect of point mutations. Natural selection was performed at each hierarchical structural level and mutations screened using Blosum 80 mutation frequency-based algorithms. Notably, SYN-AI engineered a set of three architecturally conserved docking proteins that retained motion and vibrational dynamics of native Bos taurus 14-3-3 ζ.

Keywords: 14-3-3 docking genes, synthetic protein design, time-based DNA codes, writing DNA code from scratch

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Authors: Muhammad Imran, Sarfraz Shafiq, Xiangru Tang

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Alternative splicing (AS) is an important post-transcriptional regulatory mechanism to generate transcripts variability and proteome diversity in plants. Fragrant rice (Oryza sativa L.) has a high economic and nutritional value, and the application of micronutrients regulate 2-acetyl-1-pyrroline (2-AP) production, which is responsible for aroma in fragrant rice. However, no systematic investigation of AS events in response to micronutrients (Zn) has been performed in fragrant rice. Furthermore, the post-transcriptional regulation of genes involved in 2-AP biosynthesis is also not known. In this study, a comprehensive analysis of AS events under two gradients of Zn treatment in two different fragrant rice cultivars (Meixiangzhan-2 and Xiangyaxiangzhan) was performed. A total of 386 and 598 significant AS events were found in Meixiangzhan-2 treated with low and high doses of Zn, respectively. In Xiangyaxiangzhan, a total of 449 and 598 significant AS events were found in low and high doses of Zn, respectively. Go analysis indicated that these genes were highly enriched in physiological processes, metabolism, and cellular process in both cultivars. However, genotype and dose-dependent AS events were also detected in both cultivars. By comparing differential AS (DAS) events with differentially expressed genes (DEGs), we found a weak overlap among DAS and DEGs in both fragrant rice cultivars, indicating that only a few genes are post-transcriptionally regulated in response to Zn treatment. We further report that Zn differentially regulates the expression of 2-AP biosynthesis-related genes in both cultivars, and Zn treatment altered the editing frequency of SNPs in the genes involved in 2-AP biosynthesis. Finally, we showed that epigenetic modifications associated with active gene transcription are generally enriched over 2-AP biosynthesis-related genes. Taken together, our results provide evidence of the post-transcriptional gene regulation in fragrant rice in response to Zn treatment and highlight that the 2-AP biosynthesis pathway may also be post-transcriptionally regulated through epigenetic modifications. These findings will serve as a cornerstone for further investigation to understand the molecular mechanisms of 2-AP biosynthesis in fragrant rice.

Keywords: fragrant rice, 2-acetyl-1-pyrroline, gene expression, zinc, alternative splicing, SNPs

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Authors: Maciej Sobczak, Julita Pietrzak, Tomasz Płoszaj, Agnieszka Robaszkiewicz

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Brg1, a member of SWI/SNF complex, plays a role in chromatin remodeling, therefore, regulates expression of many genes. Brg1 is an ATPase of SWI/SNF complex, thus its activity requires ATP. Through its bromodomain recognizes acetylated histone residues and evicts them, thus promoting transcriptionally active state of chromatin. One of the enzymes that is responsible for acetylation of histone residues is Ep300. It was previously shown in the literature that cooperation of Brg1 and Ep300 occurs at the promoter regions that have binding sites for E2F-family transcription factors as well as CpG islands. According to literature, approximately 20% of human cancer possess mutation in Brg1 or any other crucial SWI/SNF subunit. That phenomenon makes Brg1-Ep300 a very promising target for anti-cancer therapy. Therefore in our study, we investigated if physical interaction between Brg1 and Ep300 exists and what impact those two proteins have on key for breast cancer cells processes such as DNA damage repair and cell proliferation. Bioinformatical analysis pointed out, that genes involved in cell proliferation and DNA damage repair are overexpressed in MCF7 and MDA-MB-231 cells. Moreover, promoter regions of these genes are highly acetylated, which suggests high transcriptional activity of those sites. Notably, many of those gene possess within their promoters an E2F, Brg1 motives, as well as CpG islands and acetylated histones. Our data show that Brg1 physically interacts with Ep300, and together they regulate expression of genes involved in DNA damage repair and cell proliferation. Upon inhibiting Brg1 or Ep300, expression of vital for cancer cell survival genes such as CDK2/4, BRCA1/2, PCNA, and XRCC1 is decreased in MDA-MB-231 and MCF7 cells. Moreover, inhibition or silencing of either Brg1 or Ep300 leads to cell cycle arrest in G1. After inhibition of BRG1 or Ep300 on tested gene promoters, the repressor complex including Rb, HDAC1, and EZH2 is formed, which inhibits gene expression. These results highlight potentially significant target for targeted anticancer therapy to be introduced as a supportive therapy.

Keywords: brg1, ep300, breast cancer, epigenetics

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Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

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The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

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Authors: Dorit Olenik-Shemesh, Tali Heiman

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The rapid increase in the massive use of the internet in recent yearshas led to an increase in the prevalence of a phenomenon called 'Problematic Internet use' (PIU), an emerging, growing health problem, especially during adolescents, that poses a challenge for mental health research and practitioners. Problematic Internet use (PIU) is defined as an excessive overuse of the internet, including an inability to control time spent on the internet, cognitivepreoccupation with the Internet, and continued use in spite of the adverse consequences, which may lead to psychological, social, and academic difficulties in one's life and daily functioning. However, little is known about the nature of the nexusbetween PIU and subjective well-being among adolescents. The main purpose of the current study was to explore in depth the network of connections between PIU, sense of well-being, and fourpersonal-emotional factors (resilience, self-control, depressive mood, and loneliness) that may mediate these relationships. A total sample of 433 adolescents, 214 (49.4%) girls and 219 (50.6%) boys between the ages of 12–17 (mean = 14.9, SD = 2.16), completed self-reportquestionnaires relating to the study variables. In line with the hypothesis, analysis of a Structural Equation modeling (SEM) revealed the main following results: high levels of PIU predicted low levels of well-being among adolescents. In addition, low levels of resilience and high levels of depressivemood (together), as well as low levels of self control and high levels of depressivemood (together), as well as low levels of resilience and high levels of loneliness, mediated the relationships between PIU and well-being. In general, girls were found to be higher in PIU and inresilience than boys. The study results revealed specific implications for developing intervention programs for adolescents in the context of PIU; aiming at more balanced adjusted use of the Internet along withpreventingthe decrease in well being.

Keywords: probelmatic inetrent Use, well-being, adolescents, SEM model

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Authors: M. Lizzy Madiwani, Ignatious Ncube, Evelyn Madoroba

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This study was designed to determine the distribution of pathogenic bacteria in household raised chickens and study their virulence and antibiotic profiles. For this purpose, 40 chickens were purchased from families in the Capricorn district and sacrificed for sampling. Tissues were cultured on different bacteriological media followed by biotyping using Matrix-assisted Laser Desorption Ionization-time of Flight (MALDI-TOF). Disk diffusion test was performed to determine the antibiotic susceptibility profiles of these bacteria. Out of a total of 160 tissue samples evaluated, E. coli and Salmonella were detected in these tissues. Furthermore, determination of the pathogenic E. coli and Salmonella strains at species level using primer sets that target selected genes of interest in the polymerase chain reaction (PCR) assay was employed. The invA gene, a confirmatory gene of Salmonella was detected in all the Salmonella isolates. The study revealed that there is a high distribution of Salmonella and pathogenic E. coli in these chickens. Therefore, further studies on identification at the species level are highly recommended to provide management and sanitation practices to lower this prevalence. The antimicrobial susceptibly data generated from this study can be a valuable reference to veterinarians for treating bacterial diseases in poultry.

Keywords: antimicrobial, Escherichia coli, pathogens, Salmonella

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Authors: Hee-Jeong Ahn, Kee-Won Kim, Seung-Hoon Kim

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The knowledge of the relationship between characters can help readers to understand the overall story or plot of the literary fiction. In this paper, we present a method for extracting the specific relationship between characters from a Korean literary fiction. Generally, methods for extracting relationships between characters in text are statistical or computational methods based on the sentence distance between characters without considering Korean linguistic features. Furthermore, it is difficult to extract the relationship with direction from text, such as one-sided love, because they consider only the weight of relationship, without considering the direction of the relationship. Therefore, in order to identify specific relationships between characters, we propose a statistical method considering linguistic features, such as syntactic patterns and speech verbs in Korean. The result of our method is represented by a weighted directed graph of the relationship between the characters. Furthermore, we expect that proposed method could be applied to the relationship analysis between characters of other content like movie or TV drama.

Keywords: data mining, Korean linguistic feature, literary fiction, relationship extraction

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Authors: S. Pradhan, D. Pradhan, G. Tripathy, T. Dasmohapatra

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Suppressors of cytokine signalling (SOCS3), a newly indentified anti-apoptotic molecule is a downstream effecter of the receptor tyrosine kinase-Ras signalling pathway. Current study has uncovered that SOCS3 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS3 on MDR, we analyzed the expression of P-gp and SOCS3 by immune-histochemistry and found there was positive correlation between them. At that point we effectively interfered with RNA translation by the contamination of siRNA of SOCS3 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flowcytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS3 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: SOCS3gene, breast cancer, multidrug resistance, MDR1 gene, RNA interference

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Authors: Abdullah Alshehab

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Governments worldwide are intensely focused on digitizing public transactions to establish reliable e-government services. The advent of new digital technologies and ongoing advancements in ICT have profoundly transformed business operations. Citizen engagement and participation in e-government services are crucial for the system's success. However, it is essential to measure and enhance citizen satisfaction levels to effectively evaluate and improve these systems. Citizen satisfaction is a key criterion that allows government institutions to assess the quality of their services. There is a strong connection between information quality, service quality, and system quality, all of which directly impact user satisfaction. Additionally, both system quality and information quality have indirect effects on citizen satisfaction. A causal map, which is a network diagram representing causes and effects, can illustrate these relationships. According to the literature, the main factors influencing citizen satisfaction are trust, reliability, citizen support, convenience, and transparency. This paper investigates the causal relationships among these factors and identifies any interrelatedness between them.

Keywords: e-government services, e-satisfaction, citizen satisfaction, causal map.

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Authors: Ghazanfar Ali, Fahad N Almajhdi

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This study provides data on the viral diagnosis and molecular epidemiology of influenza A(H3N2) virus isolated in Riyadh, Saudi Arabia. Nasopharyngeal aspirates from 80 clinically infected patients in the peak of the 2010-2011 winter seasons were processed for viral diagnosis by RT-PCR. Sequencing of entire HA and NA genes of representative isolates and molecular epidemiological analysis were performed. A total of 06 patients were positive for influenza A, B and respiratory syncytial viruses by RT-PCR assays; out of these only one sample was positive for influenza A(H3N2) by RT-PCR. Phylogenetic analysis of the HA and NA gene sequences showed identities higher than 99-98.8 % in both genes. They were also similar to reference isolates in HA sequences (99 % identity) and in NA sequences (99 % identity). Amino acid sequences predicted for the HA gene were highly identical to reference strains. The NA amino acid substitutions identified did not include the oseltamivir-resistant H275Y substitution. Conclusion: Viral isolation and RT-PCR together were useful for diagnosis of the influenza A (H3N2) virus. Variations in HA and NA sequences are similar to those identified in worldwide reference isolates and no drug resistance was found.

Keywords: influenza A (H3N2), genetic characterization, viral isolation, RT-PCR, Saudi Arabia

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Authors: Radim Sip, Denisa Denglerova

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It’s impossible to capture complex phenomena, such as inclusion, with reductionism. The most common form of reductionism is the objectivist approach, where processes and relationships are reduced to entities and clearly outlined phases, with a consequent search for relationships between them. Constructivism as a paradigm and situational analysis as a methodological research portfolio represent a way to avoid the dominant objectivist approach. They work with a situation, i.e. with the essential blending of actors and their environment. Primary transactions are taking place between actors and their surroundings. Researchers create constructs based on their need to solve a problem. Concepts therefore do not describe reality, but rather a complex of real needs in relation to the available options how such needs can be met. For examination of a complex problem, corresponding methodological tools and overall design of the research are necessary. Using an original research on inclusion in the Czech Republic as an example, this contribution demonstrates that inclusion is not a substance easily described, but rather a relationship field changing its forms in response to its actors’ behaviour and current circumstances. Inclusion consists of dynamic relationship between an ideal, real circumstances and ways to achieve such ideal under the given circumstances. Such achievement has many shapes and thus cannot be captured by description of objects. It can be expressed in relationships in the situation defined by time and space. Situational analysis offers tools to examine such phenomena. It understands a situation as a complex of dynamically changing aspects and prefers relationships and positions in the given situation over a clear and final definition of actors, entities, etc. Situational analysis assumes creation of constructs as a tool for solving a problem at hand. It emphasizes the meanings that arise in the process of coordinating human actions, and the discourses through which these meanings are negotiated. Finally, it offers “cartographic tools” (situational maps, socials worlds / arenas maps, positional maps) that are able to capture the complexity in other than linear-analytical ways. This approach allows for inclusion to be described as a complex of phenomena taking place with a certain historical preference, a complex that can be overlooked if analyzed with a more traditional approach.

Keywords: constructivism, situational analysis, objective realism, reductionism, inclusion

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

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Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in NSCLC patients and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for has-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.

Keywords: long non-coding RNA NEAT1, hsa-miRNA-377-3p, E2F3, non-small cell lung cancer, tumorigenesis

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Authors: Elham Ahmadi, Mehrdad Ravanshad, Joyce Fingeroth, Mazyar Ziyaeyan, Rajesh Panigrahi, Jun Xie, Gao Guangping

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B-cell proliferative disorders often occur among persons that are T-cell compromised. These disorders are primarily EBV+ and can first present with a focal lesion. Direct introduction of oncolytic viruses into localized tumors provides theoretical advantages over chemotherapy and immunotherapy by reducing systemic toxicity, to which the immunocompromised host is most vulnerable. Widely studied as a vehicle for gene therapy, AAV has only rarely been applied to treat cancer. As a prelude to development of a therapeutic vehicle, we assessed the ability of 15 distinct recombinant AAV serotypes (rAAV1, rAAV2, rAAV3b, rAAV4, rAAV5, rAAV6, rAAV6.2, rAAV6TM, rAAV7, rAAV8, rAAVrh8, rAAV9, rAAVrh10, rAAV39, rAAV43) bearing eGFP to infect human B-cell tumor lines compared with primary B-cells in vitro. Enhanced infection of tumor lines by AAV 6.2 was demonstrated by flow cytometry. EBV superinfection of EBV negative B-cell tumor lines increased susceptibility to AAV6.2 infection. As proof of concept, AAV6.2 bearing HSV-1 thymidine kinase in place of eGFP eliminated tumor cells upon exposure to ganciclovir.

Keywords: AAV, gene therapy, lymphoma, malignancy, tropism

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Authors: L. Musak, J. Valachova, T. Vasicko, O. Osina

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Stainless steel is resistant to electrochemical corrosion by passivation. Welders are greatly exposed to welding fumes of toxic metals, which added to this steel. The content of chromium (Cr) is above 11.5%, Ni and Mo from 2 to 6.5%. The aim of the study was the evaluation of occupational exposure to Cr, chromosome analysis and valuation of individual susceptibility polymorphism of gene CCND1 c.870 G>A. The exposed group was consisted from 117 welders of stainless steels. The average age was 38.43 years and average exposure time 7.14 years. Smokers represented 40.17%. The control group consisted of 123 non-exposed workers with an average age of 39.74 years and time employment 16.67 years. Smokers accounted for 22.76%. Analysis of Cr in blood and urine was performed by atomic absorption spectrophotometry (AAS Varian SpectraAA 30P) with electrothermal decomposition of the sample in the graphite furnace. For the evaluation of chromosomal aberrations (CA) cytogenetic analysis of peripheral blood lymphocytes was used. Gene polymorphism was determined by PCR-RFLP reaction using appropriate primers and restriction enzymes. For statistic analysis the Mann-Whitney U-test was used. The mean Cr level in blood of exposed group was 0.095 µmol/l (0.019 min - max 0.504). No value exceeds the average normal value. The mean value Cr in urine was 7.9 µmol/mol creatinine (min 0.026 to max 19.26). The total number of CA was 1.86% in compared to 1.70% controls. (CTA-type 0.90% vs. 0.80% and CSA-type 0.96% vs. 0.90%). In the number of total CA statistical difference was observed between smokers and non-smokers of exposed group (S-1.57% vs. NS-2.04%, P<0.05). In CCND1 gene polymorphisms was observed the increasing of the total CA with wild-type allele (WT) via heterozygous to the VAR genotype (1.44% <1.82% <2.13%). A statistically higher incidence of CTA-type aberrations in variant genotypes between exposed and control groups was observed (1.22% vs. 0.59%, P <0.05). The work place is usually higher source of exposure to harmful factors. Workers need consistent and frequent health control. In assessing the risk of adverse effects of metals it is important to consider their persistence, behavior and bioavailability. Prolonged exposure to carcinogens may not manifest symptoms of poisoning, but delayed effects may occur, which resulted in a higher incidence of malignant tumors.

Keywords: CCND1, genotoxicity, polymorphism, stainless steel, welders

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Authors: Shokoufeh Roudashti, Shahin Bahari, Fakhri Haghi, Habib Zeighami, Ghazal Naderi, Paniz Shirmast

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Background: Mycobacterium tuberculosis complex (MTBC) causes tuberculosis (TB) in humans and animals. Mycobacterium MTBC is one of the most important species of zoonotic pathogens that can be transmitted from cattle to humans. The disease can transmit to human by direct contact with the infected animals, drinking unpasteurized milk and consumption of uncooked meat. The presence of these opportunistic, pathogenic bacteria in bovine milk has emerged as a public-health concern, especially among individuals who consume raw milk. Tuberculosis MTBC is the predominant infectious cause of morbidity and morality worldwide, It is estimated that one third of the world population (approx. 1.8 billion persons) is infected with M. tuberculosis and each year there are 8 million new cases worldwide. The aim of this study, to detect Mycobacterium MTBC in raw milk samples using polymerase chain reaction (PCR). Materials and Methods: In the present study, 60 raw milk samples were collected from rural areas in Zanjan, Iran. After extraction of DNAs and using special primers for Is6110 gene as a marker, PCR was applied to detect the presence or non-presence of the related gene. Results: According to the findings of this study, 8 (13.5 %) out of 60 milk samples were positive for Mycobacterium spp (P < 0.1). Conclusions: The Outbreak of genus Mycobacteria spp in milk samples were determined to be relatively high in Zanjan, Iran.

Keywords: Mycobacteria spp, raw milk, PCR, Zanjan

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Authors: Swarkar Sharma, Ekta Rai, Ankit Mahajan, Parvinder Kumar, Manoj K Dhar, Sushil Razdan, Kumarasamy Thangaraj, Carol Wise, Shiro Ikegawa M.D., K.K. Pandita M.D.

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Rare disorders are poorly understood hence, remain uncharacterized or patients are misdiagnosed and get poor medical attention. A rare mysterious skeletal disorder that remained unidentified for decades and rendered many people physically challenged and disabled for life has been reported in an isolated remote village ‘Arai’ of Poonch district of Jammu and Kashmir. This village is located deep in mountains and the population residing in the region is highly consanguineous. In our survey of the region, 70 affected people were reported, showing similar phenotype, in the village with a population of approximately 5000 individuals. We were able to collect samples from two multi generational extended families from the village. Through Whole Exome sequencing (WES), we identified a rare variation NM_003880.3:c.156C>A NP_003871.1:p.Cys52Ter, which results in introduction of premature stop codon in WISP3 gene. We found this variation perfectly segregating with the disease in one of the family. However, this variation was absent in other family. Interestingly, a novel splice site mutation at position c.643+1G>A of WISP3 gene, perfectly segregating with the disease was observed in the second family. Thus, exploiting WES and putting different evidences together (familial histories and genetic data, clinical features, radiological and biochemical tests and findings), the disease has finally been diagnosed as a very rare recessive hereditary skeletal disease “Progressive Pseudorheumatoid Arthropathy of Childhood” (PPAC) also known as “Spondyloepiphyseal Dysplasia Tarda with Progressive Arthropathy” (SEDT-PA). This genetic characterization and identification of the disease causing mutations will aid in genetic counseling, critically required to curb this rare disorder and to prevent its appearance in future generations in the population. Further, understanding of the role of WISP3 gene the biological pathways should help in developing treatment for the disorder.

Keywords: whole exome sequencing, Next Generation Sequencing, rare disorders

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Authors: Hongmeng Su, Luyu Zhao, Yanyan Qian, Hong Fan

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Aim: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that endanger human health seriously. RNA methylation, especially N6-methyladenosine (m⁶A) and 5-methylcytosine (m⁵C), a crucial epigenetic transcriptional regulatory mechanism, plays an important role in tumorigenesis, progression and prognosis. This research aims to systematically evaluate the prognostic value of m⁶A and m⁵C modulators in HCC patients. Methods: Twenty-four modulators of m⁶A and m⁵C were candidates to analyze their expression level and their contribution to predict the prognosis of HCC. Consensus clustering analysis was applied to classify HCC patients. Cox and LASSO regression were used to construct the risk model. According to the risk score, HCC patients were divided into high-risk and low/medium-risk groups. The clinical pathology factors of HCC patients were analyzed by univariate and multivariate Cox regression analysis. Results: The HCC patients were classified into 2 clusters with significant differences in overall survival and clinical characteristics. Nine-gene risk model was constructed including METTL3, VIRMA, YTHDF1, YTHDF2, NOP2, NSUN4, NSUN5, DNMT3A and ALYREF. It was indicated that the risk score could serve as an independent prognostic factor for patients with HCC. Conclusion: This study constructed a Nine-gene risk model by modulators of m⁶A and m⁵C and investigated its effect on the clinical prognosis of HCC. This model may provide important consideration for the therapeutic strategy and prognosis evaluation analysis of patients with HCC.

Keywords: hepatocellular carcinoma, m⁶A, m⁵C, prognosis, RNA methylation

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Authors: Karthik Mittal

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This study performs an unsupervised machine learning analysis to find clusters of related SNPs which highlight biological pathways that are important for the biological mechanisms of breast cancer. Studying genetic variations in isolation is illogical because these genetic variations are known to modulate protein production and function; the downstream effects of these modifications on biological outcomes are highly interconnected. After extracting the SNPs and their effect on different types of breast cancer using the MRBase library, two unsupervised machine learning clustering algorithms were implemented on the genetic variants: a k-means clustering algorithm and a hierarchical clustering algorithm; furthermore, principal component analysis was executed to visually represent the data. These algorithms specifically used the SNP’s beta value on the three different types of breast cancer tested in this project (estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer, and breast cancer in general) to perform this clustering. Two significant genetic pathways validated the clustering produced by this project: the MAPK signaling pathway and the connection between the BRCA2 gene and the ESR1 gene. This study provides the first proof of concept showing the importance of unsupervised machine learning in interpreting GWAS summary statistics.

Keywords: breast cancer, computational biology, unsupervised machine learning, k-means, PCA

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Authors: Brianna Z. Ross, Jonathan N. Livingston

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Given that discussions of racism and racial tensions have become more salient, there is a need to evaluate the impacts of racialization among Black individuals. Racial discrimination has become one of the most common experiences within the Black American population. Likewise, Black individuals have indicated a need to address their racial identities at an earlier age than their non-Black peers. Further, Black individuals have been found at the forefront of multiple social and political movements, including but not limited to the Civil Rights Movement, Black Lives Matter, MeToo, and Say Her Name. Moreover, the present study sought to explore the predictive relationships that exist between racial discrimination, racial identity, and activism in the Black community. The results of standard and hierarchical regression analyses revealed that racial discrimination and racial identity significantly predict each other, but only racial discrimination is a significant predictor for the relationship to activism. Nonetheless, the results from this study will provide a basis for social scientists to better understand the impacts of racialization on the Black American population.

Keywords: activism, racialization, racial discrimination, racial identity

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Authors: Rajarshi Sharma, Rashidul Alam, Visavino Seleyi, Yuvila Sangtam

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The Intensity-Duration-Frequency (IDF) relationship of rainfall amounts is one of the most commonly used tools in water resources engineering for planning, design and operation of water resources project, or for various engineering projects against design floods. The establishment of such relationships was reported as early as in 1932 (Bernard). Since then many sets of relationships have been constructed for several parts of the globe. The objective of this research is to derive IDF relationship of rainfall for western watershed of Guwahati, Assam. These relationships are useful in the design of urban drainage works, e.g. storm sewers, culverts and other hydraulic structures. In the study, rainfall depth for 10 years viz. 2001 to 2010 has been collected from the Regional Meteorological Centre Borjhar, Guwahati. Firstly, the data has been used to construct the mass curve for duration of more than 7 hours rainfall to calculate the maximum intensity and to form the intensity duration curves. Gumbel’s frequency analysis technique has been used to calculate the probable maximum rainfall intensities for a period of 2 yr, 5 yr, 10 yr, 50 yr, 100 yr from the maximum intensity. Finally, regression analysis has been used to develop the intensity-duration-frequency (IDF) curve. Thus, from the analysis the values for the constants ‘a’,‘b’ &‘c’ have been found out. The values of ‘a’ for which the sum of the squared deviation is minimum has been found out to be 40 and when the corresponding value of ‘c’ and ‘b’ for the minimum squared deviation of ‘a’ are 0.744 and 1981.527 respectively. The results obtained showed that in all the cases the correlation coefficient is very high indicating the goodness of fit of the formulae to estimate IDF curves in the region of interest.

Keywords: intensity-duration-frequency relationship, mass curve, regression analysis, correlation coefficient

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Authors: Didem Kepir Savoly, Selen Demirtas Zorbaz

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This research focuses on the unique developmental stage of university students, known as emerging adulthood, which can be filled with stressors relating to academics, career aspirations, and relationships. The impact of these factors on the wellbeing and mental health of students is not well understood and requires further investigation. The aim of this study is to investigate the influence of career optimism and relationship status on the wellbeing/life satisfaction of university students. The specific hypotheses being tested are: 1) University students with higher career optimism will exhibit a higher level of life satisfaction, and 2) University students in relationships will report a higher level of life satisfaction. This research adopts a quantitative approach, utilizing scales and questionnaires to collect data from university students in Turkey. The data was collected from university students in Turkey through the administration of the Career Optimism Scale, The Satisfaction with Life Scale, and the Perceived Romantic Relationship Quality Scale. The data is then analyzed using scale implementation, correlational analysis, and group comparison. One-way ANOVA, regression, and t-test analysis techniques are employed. The research findings provide insights into the relationship between career optimism and university students’ life satisfaction, as well as the influence of relationship status on their life satisfaction. The results suggest that life satisfaction was predicted by career optimism but not by relationship status. Moreover, significant relationships between life satisfaction and relationship quality were found among the university students who were in a relationship. These results can be utilized by practitioners, particularly those in counseling centers and career services at universities, to develop tailored psychoeducational and intervention programs aimed at promoting the mental health of university students.

Keywords: career optimism, relationship status, university students, wellbeing

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Authors: Brendan Mooney

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Context: Feelings and emotions are commonly misunderstood and the terms often used interchangeably, leading to potential negative impacts on individuals' mental well-being and relationships. The distinction between these two fundamentally different experiences of human life is crucial for effective psychological practice and communication. Research Aim: The aim of this study is to outline the disparities between feelings and emotions, emphasising the significance of this differentiation in psychological practice to enhance clients' observation, decision-making, problem-solving, and communication skills. Methodology: This research utilises a conceptual model developed by the author in 2017 based on clinical experience, client observations, and feedback. The model serves to guide effective clinical practice by providing clear definitions and understanding of feelings versus emotions. Case study examples were utilised to support the efficacy of the model. Findings: The study highlights that recognising and expressing feelings rather than emotions is more empowering and conducive to resolving unresolved issues, thereby fostering better psychological well-being and interpersonal relationships. Theoretical Importance: This research underscores the importance of clarifying fundamental definitions related to feelings and emotions in enhancing psychological interventions and preventing various relationship conflicts and individual issues. Data Collection and Analysis Procedures: Data was collected through the author's clinical experience and interactions with clients, informing the development of the Feeling Emotions Mental (FEM) model. Analysis involved synthesising observations and feedback to elucidate the distinctions between feelings and emotions. Questions Addressed: What are the disparities between feelings and emotions? How does the confusion between these two fundamentally different experiences of human life impact individuals' mental well-being and relationships? Why is it essential to differentiate between feelings and emotions in psychological practice? Conclusion: The study advocates for a clear understanding of feelings versus emotions to support clients in addressing unresolved issues and improving their overall psychological functioning and communication skills, thereby preventing potential conflicts and relationship challenges.

Keywords: couples, mental, misinformation, misunderstanding, relationships

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Authors: Muhammad Naeem, Abdus Salam, Sumera Yasmin, Abir Ishtiaq

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In the present study, eighty-three wild Oreochromis aureus of different body size ranging 5.3-14.6 cm in total length were collected from the River Chenab, District Muzzafer Garh, Pakistan to investigate the parameters of length –weight, length-length relationships and condition factor in relation to size. Each fish was measured and weighed on arrival at laboratory. Log transformed regressions were used to test the allometric growth. Length-weight relationship was found highly significant (r = 0.964; P < 0.01). The values of exponent “ b” in Length–weight regression (W=aL^b), deviated from 3, showing isometric growth (b = 2.75). Results for LLRs indicated that these are highly correlated (P < 0.001). Condition factor (K) found constant with increasing body weight, however, showed negative influence with increasing total length.

Keywords: lenght-weight, Oreochromis aureus, morphometric study

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Authors: David Sarpong, Waleed Khursheed, Ernest Danquah, Erin Murphy

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Shigella is a pathogenic bacterium responsible for shigellosis, a severe diarrheal disease that claims the lives of immunocompromised individuals worldwide. To develop therapeutics against this disease, an understanding of the molecular mechanisms underlying the pathogen’s physiology is crucial. Small non-coding RNAs (sRNAs) have emerged as important regulators of bacterial physiology, including as components of toxin-antitoxin systems. In this study, we investigated the role of RyfA in S. flexneri physiology and virulence. RyfA, originally identified as an sRNA in Escherichia coli, is conserved within the Enterobacteriaceae family, including Shigella. Whereas two copies of ryfA are present in S. dysenteriae, all other Shigella species contain only one copy of the gene. Additionally, we identified a putative open reading frame within the RyfA transcript, suggesting that it may be a dual-functioning gene encoding a small protein in addition to its sRNA function. To study ryfA in vitro, we cloned the gene into an inducible plasmid and observed the effect on bacterial growth. Here, we report that RyfA production inhibits the growth of S. flexneri, and this inhibition is dependent on the contained open reading frame. In-silico analyses have revealed the presence of two divergently transcribed sRNAs, RyfB1 and RyfB2, which share nucleotide complementarity with RyfA and thus are predicted to function as anti-toxins. Our data demonstrate that RyfB2 has a stronger antitoxin effect than RyfB1. This regulatory pattern suggests a novel form of a toxin-antitoxin system in which the activity of a single toxin is inhibited to varying degrees by two sRNA antitoxins. Studies are ongoing to investigate the regulatory mechanism(s) of the antitoxin genes, as well as the downstream targets and mechanism of growth inhibition by the RyfA toxin. This study offers distinct insights into the regulatory mechanisms underlying Shigella physiology and may inform the development of new anti-Shigella therapeutics.

Keywords: sRNA, shigella, toxin-antitoxin, Type 1 toxin antitoxin

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Authors: Martina Maria Keitsch

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Critical Design (CD) confronts traditional design practice. Instead of reproducing and reinforcing contemporary perceptions of products and services, CD seeks to challenge them with the goal to stimulate debates and visions on societal innovation. CD methods comprise, among other narratives and design of critical objects. The oral presentation is based on a study that discusses concepts, methods, and applications of CD links CD to traditional design, and identifies CD benefits and challenges for design research and practice. The objective of the study is to introduce CD as an alternative for design researchers and practitioners supplementing commercially oriented design approaches. The study utilizes a literature review on CD concepts and methods based on current publications and online documents and illustrates CD practice with help of selected case studies. Findings of the study indicate that CD contribute, among others, to create new societal roles for designers, foster innovative relationships between designers and users, and encourage creativity through imaginative aesthetics.

Keywords: critical design, postmodern design theories, narratives, rhizome

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Authors: Hend Al-Ma'seb, Anwar Alkhurinej

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In the field of social work, social workers understand that it is very difficult for individuals to ask for help from therapists. Therefore, it is important to study the variables associated with seeking professional help. A total of 478 undergraduate students from Kuwait University participated voluntarily in the study. The findings for this study showed that the participants of the study have a slightly high degree of public stigma, low self–stigma, and positive attitude toward seeking professional help. In addition, the findings of the study reveal that there are significant relationships between gender, taking social work classes, thinking about receiving counseling and having social problems and participants' attitude towards seeking professional help. Furthermore, the findings of the study showed that there were significant relationships between gender, and thinking about receiving counseling, and self-stigma. The findings of the current study have implications for the field of social work in Kuwait that would help to improve the knowledge in this area.

Keywords: attitude towards help, social work, social workers, stigma

Procedia PDF Downloads 202