Search results for: in-utero gene editing

Authors: Seyed Davar Siadat, Samira Tarashi, Abolfazl Fateh, Arfa Moshiri

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Background: The global health issue of tuberculosis (TB) still affects patients in every country. TB control may not be as effective as it should be, especially when resistant strains are involved. In this regard, mycobacterial MTases play a major role in tuberculosis, but the mechanisms underlying their function have yet to be fully deciphered. Methods: Five resistant isolates of M.tb were accumulated. As a reference strain, M.tb H37Rv (ATCC 27249) was used. For this analysis, seven putative mycobacterial MTase genes (Rv0645c, Rv1694, Rv2966c, Rv3919c, Rv2756c, Rv1988, and Rv3263), as well as Rv1392 as SAM synthase, were selected. Comparing mutations and expression levels of MTases in different strains was accomplished by PCR-sequencing and qRT-PCR. The relative expression levels of these genes were calculated using the 2 -ΔΔCt method. Results: The Rv3919c gene (T to G in codon 341) and Rv1392 gene (G to A in codon 97) were the only mutations found in the INHR strain. In all sensitive and resistant isolates, Rv0645c, Rv3263, Rv2756c, and Rv2966c were overexpressed. However, the expression of Rv1988 and Rv3919c decreased in the sensitive strains, whereas the expression of Rv1694 increased. There was also a decreased expression of Rv1392 in the INHR isolate. Conclusion: The presence of mycobacterial MTases as well as resistance to antibiotics were found to be correlated in M.tb strains. Undoubtedly, there are some MTases that are associated with the virulence process. It is necessary to conduct additional studies to fully explore the impact of mycobacterial MTases within specific strains of M.tb to develop novel diagnostic and treatment strategies.

Keywords: mycobacterium tuberculosis, drug resistance, methyltransferases, s-adenosylmethionine

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Authors: J. Areerut

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Experimental Film Class Project is supported by the Institute for Research and Development at Suan Sunandha Rajabhat University. This project is purported to provide academic and professional services to improve the quality standards of the community and locals in accordance with the mission of the university, which is to improve and expand knowledge for the community and to develop and transfer such knowledge and professions to the next generation. Eventually, it leads to sustainable development because the development of human resources is deemed as the key for sustainable development. Moreover, the Experimental Film Class is an integral part of the teaching of film production at Suan Sunandha International School of Art (SISA). By means of giving opportunities to students for participation in projects by sharing experience, skill and knowledge and participation in field activities, it helps students in the film production major to enhance their abilities and potentials as preparation for their readiness in the marketplace. Additionally, in this class, we provide basic film knowledge, screenwriting techniques, editing and subtitles including uploading videos on social media such as YouTube and Facebook for the participant students.

Keywords: experimental film class, Watbangkapom School, participant students, basic of film production, film workshop

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Authors: Mukta Singh, Ratan Kumar Saha, Himadri Saha, Paramveer Singh

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The present study evaluated the effect of sub-lethal doses of antifungal drug miconazole nitrate (MCZ) on immunological responses including immune-related gene expression and its role as a prophylactic drug against S. parasitica in Labeo rohita fingerlings. Fish were fed with sub lethal doses of MCZ i.e., T1- 6.30 mg MCZ kgBW⁻¹, T2- 12.61 mg MCZ kgBW⁻¹ and T3- 25.22 mg MCZ kgBW⁻¹ and sampling was done at different time intervals for 240 h. Immunological parameters viz. lysozyme activity, oxygen radical production and plasma anti-protease activity showed significant enhancement (p < 0.05) in fish fed with T2 and T3 doses. Significant reduction in plasma protein content was observed in all the dietary groups as compared to control. Expression of immune-relevant genes like TLR-22 and β2-M showed significantly higher expression at six h and 24 h of sampling in both liver and head-kidney. However, these genes showed a down-regulation after 120 h of sampling in both the tissues. Preventive efficacy study showed that single dose of MCZ provides protection against oomycetes up to the fourth day of infection. Significantly higher mortality was observed in control diet-fed fish as compared to fish fed with MCZ medicated diet. Thus, from the study, it can be concluded that the MCZ can act as a potent antifungal agent for preventing oomycetes infection as well as to enhance the immune response.

Keywords: antifungal, immune gene, immunological, miconazole nitrate, prophylactic

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Authors: Mahmoodreza Tahamtan

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Background: Malignant surface epithelial ovarian tumors (SEOT) account for approximately 90% of primary ovarian cancer. Wilms tumor gene (WT1) product was defined as a tumor suppressor gene, but today it is considered capable of performing oncogenic functions. There seems to be differences in WT1 expression patterns among SEOT subtypes. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Materials and Methods: Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors, 3 mucinous cystadenocarcinomas, 10 borderline mucinous tumors, 7 endometrioid ovarian carcinomas, 3 clear cell carcinomas, 1 malignant Brenner tumor, 2 metastatic adenocarcinomas, and 6 endometrial adenocarcinomas. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Results: Of the 35 cases of ovarian serous cystadenocarcinoma, 30(85.7%) were diffusely positive (3+,4+),4 showed reactivity of < 50% of the tumor cells (1+,2+), and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. All the mucinous tumors(n:13), endometrioid carcinomas (n: 7), clear cell carcinomas (n: 3), metastatic adenocarcinomas (n: 2) and primary endometrial carcinomas (n:6) were negative. The single malignant Brenner tumor showed a positive reaction for WT1(4+) Conclusion: WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors (especially endometrioid subtype) and metastatic carcinomas (especially endometrial serous carcinoma), other than malignant mesothelioma. We cannot rely to the degree of expression inorder to separate high grade borderline serous tumors from low grade ones.

Keywords: WT1, ovary, epithelial tumors, malignant

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Authors: M. Al Zallouha, Y. Landkocz, J. Brunet, R. Cousin, J. M. Halket, E. Genty, P. J. Martin, A. Verdin, D. Courcot, S. Siffert, P. Shirali, S. Billet

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Toluene is one of the most used Volatile Organic Compounds (VOCs) in the industry. Amongst VOCs, Benzene, Toluene, Ethylbenzene and Xylenes (BTEX) emitted into the atmosphere have a major and direct impact on human health. It is, therefore, necessary to minimize emissions directly at source. Catalytic oxidation is an industrial technique which provides remediation efficiency in the treatment of these organic compounds. However, during operation, the catalysts can release some compounds, called byproducts, more toxic than the original VOCs. The catalytic oxidation of a gas stream containing 1000ppm of toluene on Pd/α-Al2O3 can release a few ppm of benzene, according to the operating temperature of the catalyst. The development of new catalysts must, therefore, include chemical and toxicological validation phases. In this project, A549 human lung cells were exposed in air/liquid interface (Vitrocell®) to gas mixtures derived from the oxidation of toluene with a catalyst of Pd/α-Al2O3. Both exposure concentrations (i.e. 10 and 100% of catalytic emission) resulted in increased gene expression of Xenobiotics Metabolising Enzymes (XME) (CYP2E1 CYP2S1, CYP1A1, CYP1B1, EPHX1, and NQO1). Some of these XMEs are known to be induced by polycyclic organic compounds conventionally not searched during the development of catalysts for VOCs degradation. The increase in gene expression suggests the presence of undetected compounds whose toxicity must be assessed before the adoption of new catalyst. This enhances the relevance of toxicological validation of such systems before scaling-up and marketing.

Keywords: BTEX toxicity, air/liquid interface cell exposure, Vitrocell®, catalytic oxidation

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Authors: S. Hannah Elizabeth, A. Panneerselvam

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Objective: The main objective was to evaluate the degradative properties of Bacillus cereus sp TUHP2 isolated from TNT-Polluted soils in the Vellore District, Tamil Nadu, India. Methods: Among the 3 bacterial genera isolated from different soil samples, one potent TNT degrading strain Bacillus cereus sp TUHP2 was identified. The morphological, physiological and the biochemical properties of the strain Bacillus cereus sp TUHP2 was confirmed by conventional methods and genotypic characterization was carried out using 16S r-DNA partial gene amplification and sequencing. The broken down by products of DNT in the extract was determined by Gas Chromatogram- Mass spectrometry (GC-MS). Supernatant samples from the broth studied at 24 h interval were analyzed by HPLC analysis and the effect on various nutritional and environmental factors were analysed and optimized for the isolate. Results: Out of three isolates one strain TUHP2 were found to have potent efficiency to degrade TNT and revealed the genus Bacillus. 16S rDNA gene sequence analysis showed highest homology (98%) with Bacillus cereus and was assigned as Bacillus cereus sp TUHP2. Based on the energy of the predicted models, the secondary structure predicted by MFE showed the more stable structure with a minimum energy. Products of TNT Transformation showed colour change in the medium during cultivation. TNT derivates such as 2HADNT and 4HADNT were detected by HPLC chromatogram and 2ADNT, 4ADNT by GC/MS analysis. Conclusion: Hence this study presents the clear evidence for the biodegradation process of TNT by strain Bacillus cereus sp TUHP2.

Keywords: bioremediation, biodegradation, biotransformation, sequencing

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Authors: Pei-Ying Lo, Jing-Hao Ciou, Kai-Cheng Yang, Jia-Huei Zheng, Shih-Hsiang Huang, Kuen-Chan Lee, Er-Chieh Cho

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As-produced CNTs are insoluble in all organic solvents and aqueous solutions have imposed limitations to the use of CNTs. Therefore, how to debundle carbon nanotubes and to modify them for further uses is an important issue. There are several methods for the dispersion of CNTs in water using covalent attachment of hydrophilic groups to the surface of tubes. These methods, however, alter the electronic structure of the nanotubes by disrupting the network of sp2 hybridized carbons. In order to keep the nanotubes’ intrinsic mechanical and electrical properties intact, non-covalent interactions are increasingly being explored as an alternative route for dispersion. Apart from conventional surfactants such as sodium dodecylsulfate (SDS) or sodium dodecylbenzenesulfonate (SDBS) which are highly effective in dispersing CNTs, biopolymers have received much attention as dispersing agents due to the anticipated biocompatibility of the dispersed CNTs. Also, The pyrenyl group is known to interact strongly with the basal plane of graphene via π-stacking. In this study, a highly re-dispersible biopolymer is reported for the synthesis of pyrene-modified poly-L-lysine (PBPL) and poly(D-Glu, D-Lys) (PGLP). To provide the evidence of the safety of the PBPL/CNT & PGLP/CNT materials we use in this study, H1299 and HCT116 cells were incubated with PBPL/CNT & PGLP/CNT materials for toxicity analysis, MTS assays. The results from MTS assays indicated that no significant cellular toxicity was shown in H1299 and HCT116 cells. Furthermore, the fluorescence marker fluorescein isothiocyanate (FITC) was added to PBPL & PGLP dispersions. From the fluorescent measurements showed that the chemical functionalisation of the PBPL/CNT & PGLP/CNT conjugates with the fluorescence marker were successful. The fluorescent PBPL/CNT & PGLP/CNT conjugates could find application in medical imaging. In the next step, the GFP gene is immobilized onto PBPL/CNT conjugates by introducing electrostatic interaction. GFP-transfected cells that emitted fluorescence were imaged and counted under a fluorescence microscope. Due to the unique biocompatibility of PBPL modified CNTs, the GFP gene could be transported into H1299 cells without using antibodies. The applicability of such soluble and chemically functionalised polypeptide/CNT conjugates in biomedicine is currently investigated. We expect that this polypeptide/CNT system will be a safe and multi-functional nanomedical delivery platform and contribute to future medical therapy.

Keywords: carbon nanotube, nanotoxicology, GFP transfection, polypeptide/CNT hybrids

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Authors: Ratneev Kaur, Tajinder Kaur, Anupam Kaur

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Introduction: Polycystic Ovary Syndrome (PCOS) is a heterogenous disorder of endocrine system among women of reproductive age. PCOS is characterized by hyperandrogenism, anovulation, polycystic ovaries, hirsutism, obesity, and hyperinsulinemia. Several pathways are implicated in its etiology including the metabolic pathway of steroid hormone synthesis regulatory pathways. PCOS is an androgen excess disorder, genes operating in steroidogenesis may alter pathogenesis of PCOS. The cytochrome P450scc is a cholesterol side chain cleavage enzyme coded by CYP11A1 gene and catalyzes conversion of cholesterol to pregnenolone, the initial and rate-limiting step in steroid hormone synthesis. It is postulated that polymorphisms in this gene may play an important role in the regulation of CYP11A1 expression and leading to increased or decreased androgen production. The present study will be the first study from north India to best of our knowledge, to analyse the association of CYP11A1 (rs11632698) polymorphism in women suffering from PCOS. Methodology: The present study was approved by ethical committee of Guru Nanak Dev University in consistent with declaration of Helsinki. A total of 300 samples (150 PCOS cases and 150 controls) were recruited from Hartej hospital, for the present study. Venous blood sample (3ml) was withdrawn from women diagnosed with PCOS by doctor, according to Rotterdam 2003 criteria and from healthy age matched controls only after informed consent and detailed filled proforma. For molecular genetics analysis, blood was stored in EDTA vials. After DNA isolation by organic method, PCR-RFLP approach was used for genotyping and association analysis of rs11632698 polymorphism. Statistical analysis was done to check for significance of selected polymorphism with PCOS. Results: In 150 PCOS cases, the frequency of AA, AG and GG genotype was found to be 48%, 35%, and 13% compared to 62%, 27% and 8% in 150 controls. The major allele (A) and minor allele (G) frequency was 68% and 32% in cases and 78% and 22% in controls. Minor allele frequency was higher in cases as compared to controls, as well as the distribution of genotype was observed to be statistically significant (ᵡ²=6.525, p=0.038). Odds ratio in dominant, co-dominant and recessive models observed was 1.81 (p=0.013), 1.54 (p=0.012) and 1.77 (p=0.132) respectively. Conclusion: The present study showed statistically significant association of rs11632698 with PCOS (p=0.038) in North Indian women.

Keywords: polycystic ovary syndrome, CYP11A1, rs11632698, hyperandrogenism

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Authors: Samira Khalaji, , Fenneke Klein Jan, Kay-E. Gottschalk, Eugenia Makrantonaki, Karin Scharffetter-Kochanek

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Biological aging is a multi-dimensional process that takes place over a whole range of scales from the nanoscopic alterations within individual cells, over transformations in tissues and organs and to changes of the whole organism. On the single cell level, aging involves mutation of genes, differences in gene expression levels as well as altered posttranslational modifications of proteins. A variety of proteins is affected, including proteins of the cell cytoskeleton and migration machinery. Previous work quantified the expression of cytoskeleton proteins on the gene and protein levels in senescent and young fibroblasts. Their results show that senescent skin fibroblasts have an upregulated expression of the intermediate filament (IF) protein vimentin in contrast to actin and tubulin, which are downregulated. IFs play an important role in providing mechanical stability of cells. However, the mechanical properties of IFs depending on cellular senescence or age of the donor has not been studied so far. Hence, we employed passive microrheology on primary human dermal fibroblasts from female donors with age of 28 years (young) and 86 years (old) as model of in vivo aging and human normal dermal fibroblast from 11-year old male with CPD 17-35 (young) and CPD 58-59 (senescence) as a model of in vitro replicative senescence. In contrast to the expectations, our primary results show no significant differences in the viscoelastic properties of fibroblasts depending on age of the donor or cellular replicative senescence.

Keywords: aging, cytoskeleton, fibroblast, mechanical properties

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Authors: Renata Checiches, Thierry Coche, Nicolas F. Delahaye, Albert Linder, Fernando Ulloa Montoya, Olivier Gruselle, Karen Langfeld, An de Creus, Bart Spiessens, Vincent G. Brichard, Jamila Louahed, Frédéric F. Lehmann

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Background: The RNA-expression levels of cancer-testis antigens MAGE A3 and PRAME were determined in resected tissue from patients with primary non-small-cell lung cancer (NSCLC) and related to clinical outcome. EGFR, KRAS and BRAF mutation status was determined in a subset to investigate associations with MAGE A3 and PRAME expression. Methods: We conducted a single-centre, uncontrolled, retrospective study of 1260 tissue-bank samples from stage IA-III resected NSCLC. The prognostic value of antigen expression (qRT-PCR) was determined by hazard-ratio and Kaplan-Meier curves. Results: Thirty-seven percent (314/844) of tumours expressed MAGE-A3, 66% (723/1092) expressed PRAME and 31% (239/839) expressed both. Respective frequencies in squamous-cell tumours and adenocarcinomas were 43%/30% for MAGE A3 and 80%/44% for PRAME. No correlation with stage, tumour size or patient age was found. Overall, no prognostic value was identified for either antigen. A trend to poorer overall survival was associated with MAGE-A3 in stage IIIB and with PRAME in stage IB. EGFR and KRAS mutations were found in 10.1% (28/311) and 33.8% (97/311) of tumours, respectively. EGFR (but not KRAS) mutation status was negatively associated with PRAME expression. Conclusion: No clear prognostic value for either PRAME or MAGE A3 was observed in the overall population, although some observed trends may warrant further investigation.

Keywords: MAGE A3, PRAME, cancer-testis gene, NSCLC, survival, EGFR

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Aizati N. A. Daud, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Pieter Van Der Vlies, Eelko Hak, Rolf M. F. Berger, Henk Groen, Bob Wilffert

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Prenatal use of SRIs was previously associated with Congenital Heart Anomalies (CHA). The aim of the study is to explore whether pharmacogenetics plays a role in this teratogenicity using a gene-environment interaction study. A total of 33 case-mother dyads and 2 mother-only (children deceased) registered in EUROCAT Northern Netherlands were included in a case-only study. Five case-mother dyads and two mothers-only were exposed to SRIs (paroxetine=3, fluoxetine=2, venlafaxine=1, paroxetine and venlafaxine=1) in the first trimester of pregnancy. The remaining 28 case-mother dyads were not exposed to SRIs. Ten genes that encode the enzymes or proteins important in determining fetal exposure to SRIs or its mechanism of action were selected: CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6), ABCB1 (placental P-glycoprotein), SLC6A4 (serotonin transporter) and serotonin receptor genes (HTR1A, HTR1B, HTR2A, and HTR3B). All included subjects were genotyped for 58 genetic variations in these ten genes. Logistic regression analyses were performed to determine the interaction odds ratio (OR) between genetic variations and SRIs exposure on the risk of CHA. Due to low phenotype frequencies of CYP450 poor metabolizers among exposed cases, the OR cannot be calculated. For ABCB1, there was no indication of changes in the risk of CHA with any of the ABCB1 SNPs in the children and their mothers. Several genetic variations of the serotonin transporter and receptors (SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 & rs6298, HTR3B rs1176744) were associated with an increased risk of CHA, but with too limited sample size to reach statistical significance. For SLC6A4 genetic variations, the mean genetic scores of the exposed case-mothers tended to be higher than the unexposed mothers (2.5 ± 0.8 and 1.88 ± 0.7, respectively; p=0.061). For SNPs of the serotonin receptors, the mean genetic score for exposed cases (children) tended to be higher than the unexposed cases (3.4 ± 2.2, and 1.9 ± 1.6, respectively; p=0.065). This study might be among the first to explore the potential gene-environment interaction between pharmacogenetic determinants and SRIs use on the risk of CHA. With small sample sizes, it was not possible to find a significant interaction. However, there were indications for a role of serotonin receptor polymorphisms in fetuses exposed to SRIs on fetal risk of CHA which warrants further investigation.

Keywords: gene-environment interaction, heart defects, pharmacogenetics, serotonin reuptake inhibitors, teratogenicity

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Authors: Wen Zhang

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The smartphone plays a significant role in media convergence, and smartphone photography is reconstructing the way we communicate and think. This article aims to explore the smartphone photography practices of urban Chinese smartphone users and images produced by smartphones from a techno-cultural perspective. The analysis consists of two types of data: One is a semi-structured interview of 21 participants, and the other consists of the images created by the participants. The findings are organised in two parts. The first part summarises the current tendencies of capturing, editing, sharing and archiving digital images via smartphones. The second part shows that food and selfie/anti-selfie are the preferred subjects of smartphone photographic images from a technical and multi-purpose perspective and demonstrates that screenshots and image texts are new genres of non-photographic images that are frequently made by smartphones, which contributes to improving operational efficiency, disseminating information and sharing knowledge. The analyses illustrate the positive impacts between smartphones and photography enthusiasm and practices based on the diffusion of innovation theory, which also makes us rethink the value of photographs and the practice of ‘photographic seeing’ from the screen itself.

Keywords: digital photography, image-text, media convergence, photographic- seeing, selfie/anti-selfie, smartphone, technological innovation

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Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

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Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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Authors: Ayesha Selwyn, Annapoorni Chandrashekar, Kumar Ashwarya, Nishant Baghel

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Project-based learning (PBL) activities are typically implemented in technology-enabled schools by highly trained teachers. In rural India, students have limited access to technology and quality education. Implementing typical PBL activities is challenging. This study details how Pratham Education Foundation’s Hybrid Learning model was used to implement two PBL activities related to music in 900 remote Indian villages with 46,000 students aged 10-14. The activities were completed by 69% of groups that submitted a total of 15,000 videos (completed projects). Pratham’s H-Learning model reaches 100,000 students aged 3-14 in 900 Indian villages. The community-driven model engages students in 20,000 self-organized groups outside of school. The students are guided by 6,000 youth volunteers and 100 facilitators. The students partake in learning activities across subjects with the support of community stakeholders and offline digital content on shared Android tablets. A training and implementation toolkit for PBL activities is designed by subject experts. This toolkit is essential in ensuring efficient implementation of activities as facilitators aren’t highly skilled and have limited access to training resources. The toolkit details the activity at three levels of student engagement - enrollment, participation, and completion. The subject experts train project leaders and facilitators who train youth volunteers. Volunteers need to be trained on how to execute the activity and guide students. The training is focused on building the volunteers’ capacity to enable students to solve problems, rather than developing the volunteers’ subject-related knowledge. This structure ensures that continuous intervention of subject matter experts isn’t required, and the onus of judging creativity skills is put on community members. 46,000 students in the H-Learning program were engaged in two PBL activities related to Music from April-June 2019. For one activity, students had to conduct a “musical survey” in their village by designing a survey and shooting and editing a video. This activity aimed to develop students’ information retrieval, data gathering, teamwork, communication, project management, and creativity skills. It also aimed to identify talent and document local folk music. The second activity, “Pratham Idol”, was a singing competition. Students participated in performing, producing, and editing videos. This activity aimed to develop students’ teamwork and creative skills and give students a creative outlet. Students showcased their completed projects at village fairs wherein a panel of community members evaluated the videos. The shortlisted videos from all villages were further evaluated by experts who identified students and adults to participate in advanced music workshops. The H-Learning framework enables students in low resource settings to engage in PBL and develop relevant skills by leveraging community support and using video creation as a tool. In rural India, students do not have access to high-quality education or infrastructure. Therefore designing activities that can be implemented by community members after limited training is essential. The subject experts have minimal intervention once the activity is initiated, which significantly reduces the cost of implementation and allows the activity to be implemented at a massive scale.

Keywords: community supported learning, project-based learning, self-organized learning, education technology

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Authors: Farideh K. Khosroushahi, Serkan Erdal, Mucip Geni̇şel

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Soil salinity is one of the major abiotic stress factors that restricts arable land and reduces crop productivity worldwide. High salt concentration adversely affects plant growth and development inducing water deficit, ionic toxicity, nutrient imbalance, and lead to oxidative stress. Although the stimulating role of mammalian sex hormones on various biological and biochemical processes under normal and stress condition have been proven, there is no study regarding with these hormone's effect on modulation of the alternative respiration pathway and AOX gene expression. In this study, changes in alternative respiration pathway in leaves of maize seedlings under salinity and the possible modulating effect of estrogen on these changes were investigated. Maize seedlings were grown in a hydroponic media for 11 days and then were exposed to salt stress for 3 days after being sprayed estrogen. The data obtained from oxygen consumption revealed that salt stress elevated cellular respiration value in the leaves. In addition, a marked increase was observed at alternative respiration level in salt-stressed seedlings. Compared to salt application alone, supplementation with estrogen resulted in a significant rise in alternative oxidase (AOX) activities. Similarly, while salt stress caused to rise in expressions of AOX gene compared to control seedlings, estrogen application resulted in further activation of these genes’ expression compared to stressed-seedlings alone. These data revealed that mitigating role of estrogen against the detrimental effects of salt stress is linked to modulation of alternative respiration pathway.

Keywords: alternative oxidase, estrogen, Ssalt stress, AOX, maize

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Authors: Michael Ngongeh Mombe

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This Paper seeks to investigate an assertion made by some colleagues that there is no need paying a human translator to translate their literary texts, that there are softwares such as Reverso that can be used to do the translation. The main objective of this study is to examine the veracity of this assertion using Reverso to translate a literary text without any post-editing by a human translator. The work is based on two theories: Skopos and Communicative theories of translation. The work is a documentary research where data were collected from published documents in libraries, on the internet and from the translation produced by Reverso. We made a comparative text analyses of both source and target texts in a bid to highlight the weaknesses and strengths of the software. Findings of this work revealed that those who advocate the use of only Machine translation do so in ignorance of the translation mistakes usually made by the software. From the review of all the 268 segments of translation, we found out that the translation produced by Reverso is fraught with errors. We therefore recommend the use of human translators to either do the translation of their literary texts or revise the translation produced by machine to conform to the skopos of the work. This paper is based on Reverso translation. Similar works in the near future will be based on the other translation softwares to determine their weaknesses and strengths.

Keywords: machine translation, human translator, Reverso, literary text

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Authors: Rozeena Shaikh, Syed M Shahid, Jamil Ahmad, Qaisar Mansoor, Muhammad Ismail, Abid Azhar

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Introduction: Diabetes mellitus (DM) is a prevalent non-communicable disease worldwide. In most high-income countries as well as middle-income and low- income countries. DM is among the top causes of deaths. DM may lead to many vascular complications like hypertension, nephropathy, retinopathy, neuropathy, and foot. Diabetic nephropathy (DN) characterized by persistent albuminuria is a leading cause of end stage renal failure (ESRF). Pathogenesis of diabetic nephropathy is implicated by the polymorphisms in genes encoding the components of reninangiotensin- aldosteron system (RAAS) which include angiotensinogen (AGT), angiotensin-II receptor and particularly angiotensin converting enzyme (ACE) gene. Method: Study subjects include 110 control, 110 patients with DM without hypertension, 110 patients with DM with hypertension and 110 patients with DN. Blood samples were collected for Biochemical analysis and PCR and sequencing for the specific region of both genes. Results: The frequency of DD genotype and D allele of ACE (I/D) was significantly (p<0.05) high in DM normotensive, DM hypertensive and DN patients when compared to control. The ACE G2350A genotypes and allele frequencies were significantly different (p<0.05) in DM hypertensive patients as compared to control and DN, while no difference was observed between DM normotensive and DN when compared to control. The genotypes and alleles of AGT (M268T) polymorphism were significantly different (p<0.05) in DM normotensive, DM hypertensive and DN when compared to control. Conclusion: The DD genotype and D allele of ACE (I/D), GG genotype and G allele of ACE (G2350A) and the TT genotype and T allele of AGT (M268T) polymorphism have shown a significant difference in genotype and allele frequencies between controls and patients.

Keywords: genetic variations, ACE, AGT, diabetes mellitus, diabetic nephropathy, Pakistan

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Authors: L. Lamola, E. Manolas, A. Krause

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Background: The incidence of childhood cancer incidence is increasing gradually in low-middle income countries, such as South Africa. Globally, there is an extensive range of familial- and hereditary-cancer syndromes, where underlying germline variants increase the likelihood of developing cancer in childhood. Next-Generation Sequencing (NGS) technologies have been key in determining the occurrence and genetic contribution of germline variants to paediatric cancer development. We aimed to design and evaluate a candidate gene panel specific to inherited cancer-predisposing genes to provide a comprehensive insight into the contribution of germline variants to childhood cancer. Methods: 32 paediatric patients (aged 0-18 years) diagnosed with a malignant tumour were recruited, and biological samples were obtained. After quality control, DNA was sequenced using an ion Ampliseq 50 candidate gene panel design and Ion Torrent S5 technologies. Sequencing variants were called using Ion Torrent Suite software and were subsequently annotated using Ion Reporter and Ensembl's VEP. High priority variants were manually analysed using tools such as MutationTaster, SIFT-INDEL and VarSome. Putative identified candidates were validated via Sanger Sequencing. Results: The patients studied had a variety of cancers, the most common being nephroblastoma (13), followed by osteosarcoma (4) and astrocytoma (3). We identified 10 pathogenic / likely pathogenic variants in 10 patients, most of which were novel. Conclusions: According to the literature, we expected ~10% of our patient population to harbour pathogenic or likely pathogenic germline variants, however, we reported about 3 times (~30%) more than we expected. Majority of the identified variants are novel; this may be because this is the first study of its kind in an understudied South African population.

Keywords: Africa, genetics, germline-variants, paediatric-cancer

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Authors: Abiodun Olayinka, Daniel Dzidzienyo, Pangirayi Tongoona, Samuel Offei, Edwige Gaby Nkouaya Mbanjo, Chiedozie Egesi, Ismail Yusuf Rabbi

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Cassava (Manihot esculenta Crantz) is a major source of starch for various industrial applications. However, the traditional cultivation and harvesting methods of cassava are labour-intensive and inefficient, limiting the supply of fresh cassava roots for industrial starch production. To achieve improved productivity and quality of fresh cassava roots through mechanized cultivation, cassava cultivars with compact plant architecture and moderate plant height are needed. Plant architecture-related traits, such as plant height, harvest index, stem diameter, branching angle, and lodging tolerance, are critical for crop productivity and suitability for mechanized cultivation. However, the genetics of cassava plant architecture remain poorly understood. This study aimed to identify the genetic bases of the relationships between plant architecture traits and productivity-related traits, particularly starch content. A panel of 453 clones developed at the International Institute of Tropical Agriculture, Nigeria, was genotyped and phenotyped for 18 plant architecture and productivity-related traits at four locations in Nigeria. A genome-wide association study (GWAS) was conducted using the phenotypic data from a panel of 453 clones and 61,238 high-quality Diversity Arrays Technology sequencing (DArTseq) derived Single Nucleotide Polymorphism (SNP) markers that are evenly distributed across the cassava genome. Five significant associations between ten SNPs and three plant architecture component traits were identified through GWAS. We found five SNPs on chromosomes 6 and 16 that were significantly associated with shoot weight, harvest index, and total yield through genome-wide association mapping. We also discovered an essential candidate gene that is co-located with peak SNPs linked to these traits in M. esculenta. A review of the cassava reference genome v7.1 revealed that the SNP on chromosome 6 is in proximity to Manes.06G101600.1, a gene that regulates endodermal differentiation and root development in plants. The findings of this study provide insights into the genetic basis of plant architecture and yield in cassava. Cassava breeders could leverage this knowledge to optimize plant architecture and yield in cassava through marker-assisted selection and targeted manipulation of the candidate gene.

Keywords: Manihot esculenta Crantz, plant architecture, DArtseq, SNP markers, genome-wide association study

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Authors: Kathy Stein, Mariola Lysson, Anja Schmidt, Beatrix Schumak, Sabine Specht, Hicham Bouabe, Jürgen Heesemann, Axel Roers, Joerg C. Kalff, Sven Wehner

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Objective: Postoperative ileus (POI) is a common complication of abdominal surgery. Monocyte infiltration is a hallmark of POI. The polarization of macrophages/monocytes in this process is not well understood. We aimed to investigate if and how M2 macrophage/monocyte differentiation is involved in POI pathogenesis. Design: POI was induced by intestinal manipulation (IM). C57Bl/6, CCR2-/-, IL-10 reporter (ITIB), IL-10-/- and LysMcre/IL-10fl/fl mice underwent IM. At various points in time leukocyte influx, gene and protein expression of cytokines, chemokines and M2 differentiation markers and intestinal motility were analyzed. Results: IM induced the postoperative expression of the M2 markers Arginase-1 and YM-1, predominantly in F4/80+Ly6C+ monocytes. Gene expression analyses indicated an IL-10-dependent, IL-4-independent M2 polarization of these monocytes. IL-10 dependency of M2 differentiation was confirmed in IL-10 deficient mice. Leukocytes, in the order of infiltrating monocytes, neutrophils, and resident macrophages were the main IL-10 producers during POI. IL-10 producing monocytes as well as M2 marker expression were almost absent in CCR2-deficient mice. However, postoperative IL-10 expression was not altered in CCR2-/- mice. The loss of M2 polarized monocytes neither protected CCR2-/- mice from nor affected resolution of POI. In contrast, IL-10 deficiency reduced postoperative neutrophil numbers and ameliorated POI. IL-10Ra expression was strongly induced in neutrophils but not in monocytes. Conclusion: We conclude that IL-10 counteracts POI resolution by activating IL-10Ra-expressing neutrophils in the late phase of disease while IL-10-dependent M2 differentiation is not pivotal to POI manifestation and resolution.

Keywords: interleukin-10, macrophages, neutrophils, postoperative ileus

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Authors: Qingfang Guo

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Isodon rubescens is rich in a variety of terpenes such as oridonin. It has important medicinal value. MYB transcription factors are involved in the regulation of plant secondary metabolic pathways. The combined transcriptomics and metabolomics analysis revealed that IrMYB55 might be involved in the regulation of the synthesis of terpenes. The function of IrMYB55 was further verified by establishing of a genetic transformation system by CRISPR/Cas9. Obtaining a virus-mediated Isodon rubescens gene silencing material. The main research results are as follows: (1) Screening IrMYB which can regulate the synthesis of terpenes. Metabolomics and transcriptomics analyses of materials with high (TJ)-and low (FL)-content populations which revealed significant differences in terpene content and IrMYB55 expression. Correlation analysis showed that the expression level of IrMYB55 had a significant correlation with the content of terpenes. (2) Establishment of a genetic transformation system of Isodon rubescens. The IrPDS gene could be knocked out by injection of Isodon rubescens cotyledon, and the transformed material showed obvious albino phenotype. Subsequently, IrMYB55 conversion material was obtained by this method. (3) The IrMYB55 silencing material was obtained. Subcellular localization indicated that IrMYB55 was located in the nucleus, indicating that it might regulate the synthesis of terpenoids through transcription. In summary, IrMYB55 that may regulate the synthesis of oridonin was dug out from the transcriptome and metabolome data. In this study, a genetic transformation system of Isodon rubescens was successfully established. Further studies showed that IrMYB55 regulated the transcription level of genes related to the synthesis of terpenoids, thereby promoting the accumulation of oridonin.

Keywords: isodon rubescens, MYB, oridonin, CRISPR/Cas9

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Authors: Chisakan Papapankiad

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The purposes of this research were 1) to study the competency of condominium managers, 2) to create the training curriculum via electronic media for condominium managers, and 3) to evaluate the training curriculum for condominium managers. The research methods included document analysis, interview, questionnaire, and a try-out. A total of 20 experts were selected to collect data by using Delphi technique. The designed curriculum was tried out with 30 condominium managers. The important steps of conducting this research included analyzing and synthesizing, creating interview questions, conducting factor analysis and developing the training curriculum, editing by experts, and trying out with sample groups. The findings revealed that there were five core competencies: leadership, human resources management, management, communication, and self-development. The training curriculum was designed and all the learning materials were put into a CD. The evaluation of the training curriculum was performed by five experts and the training curriculum was found to be cohesive and suitable for use in the real world. Moreover, the findings also revealed three important issues: 1) the competencies of the respondents after the experiment were higher than before the experiment and this had a level of significance of 0.01, 2) the competencies remained with the respondents at least 12 weeks and this also had a level of significance of 0.01, and 3) the overall level of satisfaction from the respondents were 'the highest level'.

Keywords: competency training curriculum, condominium managers, electronic media

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Authors: Tsegay Teklebrhan Gebremariam, Zhiliang, Arjan Jonker

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The study investigated that using corn gluten (CG) instead of cornmeal (CM) increased dietary sulfur shifted H₂ metabolism from methanogenesis to alternative sink and modulated microbiome in the rumen as well as hindgut segments of goats. Ruminal fermentation, CH₄ emissions and microbial abundance in goats (n = 24). The experiment was performed using a randomized block design with two dietary treatments (CM and CG with 400 g/kg DM each). Goats in CG increased sulfur, NDF and CP intake and decreased starch intake as compared with those in CM. Goats that received CG diet had decreased dissolved hydrogen (dH₂) (P = 0.01) and dissolved methane yield and emission (dCH₄) (P = 0.001), while increased dH₂S both in the rumen and hindgut segments than those fed CM. Goats fed CG had higher (p < 0.01) gene copies of microbiota and cellulolytic bacteria, whereas starch utilizing bacterial species were less in the rumen and hindgut than those fed CM. Higher (P < 0.05) methanogenic diversity and abundances of Methanimicrococcus and Methanomicrobium were observed in goats that consumed CG, whilst containing lower Methanobrevibacter populations than those receiving CM. The study suggested that goats fed corn gluten improved the gene copies of microbiota and fibrolytic bacterial species while reducing starch utilizing species in the rumen and hindgut segments as compared with that fed cornmeal. Goats consuming corn gluten had a more enriched methanogenic diversity and reduced Methanobrevibacter, a contributor to CH₄ emissions, as compared with goats fed CM. Corn gluten could be used as an alternative feed to decrease the enteric CH₄ emission in ruminant production.

Keywords: dissolved gasses, methanogenesis, microbial community, metagenomics

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Yi H. Wong, Li L. Chan, Chee O. Leong, Stephen Ambu, Joon W. Mak, Priyadashi S. Sahu

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Background: Acanthamoeba is a free-living opportunistic protist which is ubiquitously distributed in the environment. Virulent Acanthamoeba can cause fatal encephalitis in immunocompromised patients and potential blinding keratitis in immunocompetent contact lens wearers. Approximately 24 species have been identified but only the A. castellanii, A. polyphaga and A. culbertsoni are commonly associated with human infections. Until to date, the precise molecular basis for Acanthamoeba pathogenesis remains unclear. Previous studies reported that Acanthamoeba virulence can be diminished through prolonged axenic culture but revived through serial mouse passages. As no clear explanation on this reversible pathogenesis is established, hereby, we postulate that the epigenetic regulators, DNA-methyltransferases (DNMT) and histone-deacetylases (HDAC), could possibly be involved in granting the virulence plasticity of Acanthamoeba spp. Methods: Four rounds of mouse passages were conducted to revive the virulence potential of the virulence-attenuated Acanthamoeba castellanii strain (ATCC 50492). Briefly, each mouse (n=6/group) was inoculated intraperitoneally with Acanthamoebae cells (2x 105 trophozoites/mouse) and incubated for 2 months. Acanthamoebae cells were isolated from infected mouse organs by culture method and subjected to subsequent mouse passage. In vitro cytopathic, encystment and gelatinolytic assays were conducted to evaluate the virulence characteristics of Acanthamoebae isolates for each passage. PCR primers which targeted on the 2 members (DNMT1 and DNMT2) and 5 members (HDAC1 to 5) of the DNMT and HDAC gene families respectively were custom designed. Quantitative real-time PCR (qPCR) was performed to detect and quantify the relative expression of the two gene families in each Acanthamoeba isolates. Beta-tubulin of A. castellanii (Genbank accession no: XP_004353728) was included as housekeeping gene for data normalisation. PCR mixtures were also analyzed by electrophoresis for amplicons detection. All statistical analyses were performed using the paired one-tailed Student’s t test. Results: Our pathogenicity tests showed that the virulence-reactivated Acanthamoeba had a higher degree of cytopathic effect on vero cells, a better resistance to encystment challenge and a higher gelatinolytic activity which was catalysed by serine protease. qPCR assay showed that DNMT1 expression was significantly higher in the virulence-reactivated compared to the virulence-attenuated Acanthamoeba strain (p ≤ 0.01). The specificity of primers which targeted on DNMT1 was confirmed by sequence analysis of PCR amplicons, which showed a 97% similarity to the published DNA-methyltransferase gene of A. castellanii (GenBank accession no: XM_004332804.1). Out of the five primer pairs which targeted on the HDAC family genes, only HDAC4 expression was significantly difference between the two variant strains. In contrast to DNMT1, HDAC4 expression was much higher in the virulence-attenuated Acanthamoeba strain. Conclusion: Our mouse passages had successfully restored the virulence of the attenuated strain. Our findings suggested that DNA-methyltransferase (DNMT1) and histone deacetylase (HDAC4) expressions are associated with virulence potential of Acanthamoeba spp.

Keywords: acanthamoeba, DNA-methyltransferase, histone deacetylase, virulence-associated proteins

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Authors: Abubakar Abdulkareem, Nasir Haruna Soba

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Artificial intelligence (AI) is developing at a rapid pace, revolutionizing several industries, including education. This talk looks at how useful AI can be for academic writing, with an emphasis on how it can help researchers be more accurate, productive, and creative. The academic world now relies heavily on AI technologies like grammar checkers, plagiarism detectors, and content generators to help with the writing, editing, and formatting of scholarly papers. This study explores the particular uses of AI in academic writing and assesses how useful and helpful these applications may be for both students and scholars. By means of an extensive examination of extant literature and a sequence of empirical case studies, we scrutinize the merits and demerits of artificial intelligence tools utilized in academic writing. Important discoveries indicate that although AI greatly increases productivity and lowers human error, there are still issues that need to be resolved, including reliance, ethical concerns, and the potential loss of critical thinking abilities. The talk ends with suggestions for incorporating AI tools into academic settings so that they enhance rather than take the place of the intellectual rigor that characterizes scholarly work. This study adds to the continuing conversation about artificial intelligence (AI) in higher education by supporting a methodical strategy that uses technology to enhance human abilities in academic writing.

Keywords: artificial intelligence, academic writing, ai tools, productivity, ethics, higher education

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Authors: Eun-Ji Lee, Hye-Sung Park, Chan-Jung Lee, Won-Sik Kong

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We analyzed the DNA sequence of the ITS (Internal Transcribed Spacer) region of the 18S ribosomal gene and compared it with the gene sequence of T. fuciformis and Hypoxylon sp. in the BLAST database. The sequences of collected T. fuciformis and Hypoxylon sp. have over 99% homology in the T. fuciformis and Hypoxylon sp. sequence BLAST database. In order to select the optimal medium for T. fuciformis, five kinds of a medium such as Potato Dextrose Agar (PDA), Mushroom Complete Medium (MCM), Malt Extract Agar (MEA), Yeast extract (YM), and Compost Extract Dextrose Agar (CDA) were used. T. fuciformis showed the best growth on PDA medium, and Hypoxylon sp. showed the best growth on MCM. So as to investigate the optimum pH and temperature, the pH range was set to pH4 to pH8 and the temperature range was set to 15℃ to 35℃ (5℃ degree intervals). Optimum culture conditions for the T. fuciformis growth were pH5 at 25℃. Hypoxylon sp. were pH6 at 25°C. In order to confirm the most suitable carbon source, we used fructose, galactose, saccharose, soluble starch, inositol, glycerol, xylose, dextrose, lactose, dextrin, Na-CMC, adonitol. Mannitol, mannose, maltose, raffinose, cellobiose, ethanol, salicine, glucose, arabinose. In the optimum carbon source, T. fuciformis is xylose and Hypoxylon sp. is arabinose. Using the column test, we confirmed sawdust a suitable for T. fuciformis, since the composition of sawdust affects the growth of fruiting bodies of T. fuciformis. The sawdust we used is oak tree, pine tree, poplar, birch, cottonseed meal, cottonseed hull. In artificial cultivation of T. fuciformis with sawdust medium, T. fuciformis and Hypoxylon sp. showed fast mycelial growth on mixture of oak tree sawdust, cottonseed hull, and wheat bran.

Keywords: cultivation, optimal condition, tremella fuciformis, nutritional source

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